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Screening for colorectal cancer

Guideline Panel Members


Saudi Expert Panel
Dr. Nasser Al-Sanea
Dr. Alaa Salah Omar Abduljabbar
Dr. Samar AlHomoud
Dr. Majid Abdulrahman Almadi
Dr. Taghreed A. Al Shaban
Dr. Abdullah Alsuhaibani
Dr. Ahmad Alzahrani
Dr. Faisal Batwa
Dr. Abdul-Hameed Hassan
Mrs. Denise Hibbert
Dr. Randa Nooh
Dr. Mohammed Alothman (Patient representative)

McMaster University Working Group


Ms. Rebecca L. Morgan, Dr. Bram Rochwerg, Dr. Waleed Alhazzani, Dr. Jan Brozek, and Dr.
Holger Schnemann, on behalf of the McMaster Guideline Working Group

Acknowledgements
We acknowledge Dr. Ahmad Almalki for his contribution to this work.

We gratefully acknowledge Dr Rajaa Alraddadi , from the Ministry of Health for peer reviewing
this final report.

Disclosure of potential conflict of interest:


All co-authors have declared no conflict of interest.

Funding:
This clinical practice guideline was funded by the Ministry of Health, Saudi Arabia.

Address for correspondence:


Saudi Center for Evidence Based Health Care
E-mail: ebhc@moh.gov.sa
Web: http://www.moh.gov.sa/endepts/Proofs/Pages/home.aspx
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Contents
The Saudi Center for Evidence Based Health Care (EBHC) .................................................................... iv
Executive Summary................................................................................................................................. 1
Introduction ........................................................................................................................................ 1
Methodology....................................................................................................................................... 1
How to use these guidelines ............................................................................................................... 1
Key questions ...................................................................................................................................... ii
Recommendations .............................................................................................................................. ii
Scope and purpose.................................................................................................................................. 5
Introduction ............................................................................................................................................ 5
Methodology........................................................................................................................................... 5
How to use these guidelines ................................................................................................................... 6
Key questions .......................................................................................................................................... 6
Recommendations .................................................................................................................................. 7
Question 1: Should colorectal cancer (CRC) screening be used in asymptomatic average risk
population compared to no screening? .............................................................................................. 7
Question 2: Should CRC screening be used in average risk population aged 70 years or older
compared to no screening? ................................................................................................................ 9
Question 3: Should colonoscopy be used for CRC screening in asymptomatic average risk
population compared to no screening? ............................................................................................ 10
Question 4: Should flexible sigmoidoscopy (FS) be used for CRC screening in asymptomatic
average risk population compared to no screening? ....................................................................... 11
Question 5: Should CT colonography (CTC) be used for CRC screening in asymptomatic, average
risk population compared to colonoscopy?...................................................................................... 12
Question 6: Should flexible sigmoidoscopy (FS) be used for CRC screening in average risk
population compared to guaiac fecal occult blood testing (gFOBT)?............................................... 14
Question 7: Should FS be used for CRC screening in average risk population compared to
colonoscopy? .................................................................................................................................... 15
Research Priorities ............................................................................................................................ 17
References ............................................................................................................................................ 18
Appendices............................................................................................................................................ 20
Appendix 1: Evidence to Decision Tables ......................................................................................... 21
Guideline Question 1: Should colorectal cancer (CRC) screening be used in asymptomatic
average risk population compared to no screening? ................................................................... 21
Guideline Question 2: Should CRC screening be used in average risk population aged 70 years or
older compared to no screening? ................................................................................................. 29
Guideline Question 3: Should colonoscopy be used for CRC screening in asymptomatic average
risk population compared to no screening? ................................................................................. 38
Guideline Question 4: Should flexible sigmoidoscopy be used for CRC screening in asymptomatic
average risk population compared to no screening? ................................................................... 47
Guideline Question 5: Should CT colonography be used for CRC screening in average risk
population compared to colonoscopy? ........................................................................................ 55
Guideline Question 6: Should FS be used for CRC screening in average risk population compared
to guaiac fecal occult blood testing (gFOBT)?............................................................................... 66
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Guideline Question 7: Should FS be used for CRC screening in average risk population compared
to colonoscopy? ............................................................................................................................ 75
Appendix 2: Search Strategies and Results ....................................................................................... 85
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The Saudi Center for Evidence Based Health Care (EBHC)

The Saudi Centre for Evidence Based Health Care has managed and supported the coordination of
the process of clinical practice guideline (CPG) development between the methodological team from
McMaster University and the local clinical expert panel members in Saudi Arabia.

The EBHC staff members recruited local clinical experts through contacting Saudi specialist societies
and also independent experts interested in developing reliable and most up-to-date CPGs to
harmonize the treatment and provide the highest quality of health care in the kingdom of Saudi
Arabia. These experts were health care professionals of multidisciplinary backgrounds. As much as
possible, patients representatives were also included in panels.

In an effort to make national recommendations, the participating experts were professionals from
the Ministry of Health (MoH), National Guard Hospitals, King Faisal Specialist Hospital and Research
Centre (KFSHRC), University Hospitals, Security Forces Hospitals, Prince Sultan Military Medical City
(PSMMC) and from some private hospitals.

Based on a preselection of available evidence syntheses, the EBHC provided a list of potential topics
to be addressed in CPGs after thorough consultations with the local stakeholders. These topics were
further discussed with the McMaster team for important selection criteria and agreed on 12 topics
for wave 2.

The guideline panel meetings were held in Riyadh on 15th-18th March 2015 where 96 local experts
working in Saudi Arabia participated with the methodological support from 20 experts from
McMaster University and its partners from the American University of Beirut, Lebanon, and the
University of Freiburg, Germany, in providing high quality recommendations for common and
important clinical conditions in the Kingdom.

The Saudi Centre for EBHC supports the efforts for dissemination of the CPGs by publishing online
the full reports of the CPGs, facilitates writing concise versions of the CPGs for publication in peer
reviewed medical journals, sending hard copies to hospitals and health care centers. Finally, a
mobile App has been introduced in KSA to facilitate the dissemination efforts of the completed
practice guidelines.

The staff members at the Saudi Centre for EBHC:


Dr. Zulfa Al Rayess, Consultant Family Medicine, Head of Saudi Center for EBHC
Dr. Yaser Adi, Scientific Advisor for the Saudi Centre for EBHC
Miss Nourah Al Moufarreh, Project Manager, Saudi Center for EBHC
Screening for colorectal cancer
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(Grading of Recommendations, Assessment,


Executive Summary Development and Evaluation) approach.3 We
used this information to prepare GRADE
Introduction evidence-to-decision frameworks that served
the guideline panel to follow the structured
Colorectal cancer is a major health problem consensus process and transparently
leading to more than 550,000 deaths document all decisions made during the
annually, with many developing among meeting (see Appendix 1). The guideline panel
persons without identifiable risk factors.1 met in Riyadh on March 15 & 16, 2015 and
Evidence suggests that the identification and formulated all recommendations during this
removal of precancerous adenomas can meeting. Potential conflicts of interests of all
prevent the cancer from developing. Multiple panel members were managed according to
screening modalities exist to identify the World Health Organization (WHO) rules.4
colorectal cancer among asymptomatic
persons at average risk. As a quality measure for any practice
guideline prior to publication, the final report
Given the importance of this topic, the have been externally peer reviewed by a
Ministry of Health of the Kingdom of Saudi methodological expert who has not been
Arabia with the support of the McMaster involved in this guideline development.
University working group produced practice
guidelines to assist health care providers in How to use these guidelines
evidence-based decision-making on the
screening for colorectal cancer. The guideline working group developed and
graded the recommendations and assessed
Methodology the quality of the supporting evidence
according to the GRADE approach.5 Quality of
This practice guideline is a part of the larger evidence (confidence in estimates of effects)
initiative of the Ministry of Health of the is categorized as: high, moderate, low, or very
Kingdom of Saudi Arabia (KSA) to establish a low based on consideration of risk of bias,
program of rigorous development of indirectness, inconsistency, imprecision and
guidelines. The ultimate goals are to provide publication bias of the estimates as well as
guidance for clinicians and other healthcare factors that lead to upgrading the quality of
decision makers and reduce unnecessary the evidence. High quality evidence indicates
variability in clinical practice across the that we are very confident that the true effect
Kingdom. lies close to that of the estimate of the effect.
Moderate quality evidence indicates
The Saudi expert guideline panel selected the moderate confidence, and that the true effect
topic of this guideline and all healthcare is likely close to the estimate of the effect, but
questions addressed herein using a formal there is a possibility that it is substantially
prioritization process. For all selected different. Low quality evidence indicates that
questions we updated existing systematic our confidence in the effect estimate is
reviews on colorectal screening.2 We also limited, and that the true effect may be
conducted systematic searches for substantially different. Finally, very low
information that was required to develop full quality evidence indicates that the estimate of
guidelines for the KSA, including searches for effect of interventions is very uncertain, the
information about patients values and true effect is likely to be substantially
preferences, and costs and resource use different from the effect estimate and further
specific to the Saudi context. Based on the research is likely to have important potential
systematic reviews we prepared summaries of for reducing the uncertainty.
available evidence supporting each
recommendation following the GRADE
Screening for colorectal cancer
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The strength of recommendations is (see Table 1).6 Understanding the


expressed as either strong (guideline panel interpretation of these two grades is essential
recommends) or conditional (guideline for sagacious clinical decision making.
panel suggests) and has explicit implications

Table 1: Interpretation of strong and conditional (weak) recommendations

Implications Strong recommendation Conditional (weak) recommendation


For patients Most individuals in this situation The majority of individuals in this
would want the recommended situation would want the suggested
course of action and only a small course of action, but many would not.
proportion would not. Formal
decision aids are not likely to be
needed to help individuals make
decisions consistent with their values
and preferences.
For clinicians Most individuals should receive the Recognize that different choices will be
intervention. Adherence to this appropriate for individual patients and
recommendation according to the that you must help each patient arrive
guideline could be used as a quality at a management decision consistent
criterion or performance indicator. with his or her values and preferences.
Decision aids may be useful helping
individuals making decisions consistent
with their values and preferences.
For policy makers The recommendation can be adapted Policy making will require substantial
as policy in most situations debate and involvement of various
stakeholders.

Key questions 7. Should FS be used for CRC screening in


average risk population compared to
1. Should colorectal cancer (CRC) screening colonoscopy?
be used in asymptomatic average risk
population compared to no screening?
2. Should CRC screening be used in average Recommendations
risk population aged 70 years or older
compared to no screening? Recommendation 1: The panel recommends
3. Should colonoscopy be used for CRC using colorectal cancer screening for
screening in asymptomatic average risk asymptomatic, average risk persons rather
population compared to no screening? than no screening. (strong recommendation,
4. Should flexible sigmoidoscopy (FS) be low quality evidence)
used for CRC screening in asymptomatic
average risk population compared to no Remarks:
screening? The panel agreed that they were making
5. Should CT colonography (CTC) be used for the most informed decision despite low
CRC screening in asymptomatic average quality of evidence and that future
risk population compared to research would be unlikely to change this
colonoscopy? recommendation.
6. Should FS be used for CRC screening in
average risk population compared to Recommendation 2: The panel suggests not
guaiac fecal occult blood testing (gFOBT)? using colorectal cancer screening for
asymptomatic persons at average risk aged
Screening for colorectal cancer
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70 years or older. (conditional patients. (conditional recommendation, low


recommendation, low quality evidence) quality evidence)

Remarks: Remarks:
Consider that some individual patients The decision to use colonoscopy instead
might still benefit from screening (if of CT colonography should be driven by
healthy, lack comorbidities, and life feasibility and availability of the tests, as
expectancy is judged to be greater than sometimes the wait for endoscopy
10 years at time of screening) services is too long for asymptomatic
Consider additional resources needed for patient screening
mental health and social support if cancer For patients preferring non-invasive
is identified and surgery or other screening, they may choose to undergo
treatment may not be appropriate or CT colonography initially with the
offered understanding they would still be
subjected to the bowel preparation
Recommendation 3: The panel recommends procedure and that CT colonography still
screening colonoscopy rather than no has small risks of complications and the
screening for asymptomatic, average risk risk of radiation exposure
population. (strong recommendation, low
quality evidence) Recommendation 6: The panel suggests using
flexible sigmoidoscopy rather than guaiac
Remarks: fecal occult blood test (gFOBT) for colorectal
Colonoscopy is considered the gold cancer screening among asymptomatic,
standard and there is high confidence in average risk persons in the Kingdom of Saudi
the magnitude of the association, even Arabia. (conditional recommendation, very
though that is based on low quality low quality evidence)
evidence
As with the other recommendations a Remarks:
small amount of uncertainty is recognized gFOBT is a less sensitive method, but
given the indirect evidence regarding depending on the availability of other
resources, values and preference, health screening modalities, setting, and
inequalities, and feasibility resources it can still be used
FS is often done in combination with FOBT
Recommendation 4: The panel recommends or FIT testing to ensure the entire colon is
using flexible sigmoidoscopy (FS) for screened
colorectal cancer screening rather than no
screening for asymptomatic persons at Recommendation 7: The panel suggests using
average risk. (strong recommendation, colonoscopy rather than flexible
moderate quality evidence) sigmoidoscopy for colorectal cancer
screening among asymptomatic, average risk
Remarks: persons. (conditional recommendation, low
This recommendation refers to FS quality evidence)
screening every 5 years when combined
with annual fecal occult blood (FOBT) or Remarks:
fecal immunochemical (FIT) testing or FS needs to be done at least twice as
every 3 years without annual FIT testing often (every 3-to-5 years depending on
whether FIT provided annually)
Consider that FS misses right-sided
Recommendation 5: The panel suggests using disease
colonoscopy rather than CT colonography for Benefit of FS may be more if combined
diagnosis of asymptomatic, average risk with FOBT or FIT
Screening for colorectal cancer
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Screening for colorectal cancer
5

recommendations), and screening


Scope and purpose technologies (5 recommendations).

The purpose of this document is to provide


guidance about colorectal cancer (CRC) Methodology
screening. The target audience of these
guidelines includes gastroenterologists, To facilitate the interpretation of these
oncologists, nurse endoscopists, general guidelines; we briefly describe the
practitioners, and asymptomatic patients at methodology we used to develop and grade
average risk in the Kingdom of Saudi Arabia recommendations and quality of the
(KSA). Other health care professionals and supporting evidence.
policy makers may also benefit from these
guidelines. The Saudi expert guideline panel selected the
topic of this guideline and all healthcare
Given the importance of this topic, the questions addressed herein using a formal
Ministry of Health (MoH) of Saudi Arabia with prioritization process. For the selected
the support of the McMaster University questions we updated existing systematic
working group produced practice guidelines reviews on population-level colorectal cancer
to assist health care providers in evidence- screening and screening technologies2. For
based decision-making. This practice guideline each question, the McMaster guideline
is a part of the larger initiative of the Ministry working group updated the search strategy to
of Health of Saudi Arabia to establish a identify new studies and/or new systematic
program of rigorous adaptation and de novo reviews. When relevant, the meta-analyses
development of guidelines in the Kingdom; were updated. We also conducted systematic
the ultimate goal being to provide guidance searches for information that was required to
for clinicians and other healthcare decision develop full guidelines for the KSA, including
makers and reduce unnecessary variability in searches for information about patients
clinical practice across the Kingdom. values and preferences, and costs and
resource use specific to the Saudi context (see
Appendix 2).
Introduction
Next, we developed for each question an
Colorectal cancer is a major health problem evidence profile and an evidence-to-decision
leading to more than 550,000 deaths (EtD) table following the GRADE (Grading of
annually, with many developing among Recommendations, Assessment, Development
persons without identifiable risk factors1. and Evaluation) approach and shared them
Evidence suggests that the identification and with the panel members (see Appendix 1).3,9
removal of precancerous adenomas can The guideline panel was invited to provide
prevent the cancer from developing7. Multiple additional information, particularly when
screening modalities exist to identify published evidence was lacking. The final step
colorectal cancer among asymptomatic consisted of an in-person meeting of the
persons at average risk. guideline panel in Riyadh on March 15 & 16,
2015 to formulate the final recommendations.
In 2010, the Kingdom of Saudi Arabia reported We used the GRADE evidence-to-decision
that 10.4% of all diagnosed cancers were frameworks to follow a structured consensus
colorectal8. This is the predominant cancer process and transparently document all
detected among males and the third among decisions made during the meeting. Potential
females8. conflicts of interests of all panel members
were managed according to the World Health
These recommendations covering the Organization (WHO) rules.4
following topics: population-level screening of
asymptomatic persons at average risk (2
Screening for colorectal cancer
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Grading of the quality of evidence methodological expert who has not been
The GRADE working group defines the quality involved in this guideline development.
of evidence as the extent of our confidence
that the estimate of an effect is adequate to
support a particular decision or How to use these
5
recommendation. We assessed the quality of
evidence using the GRADE approach.
guidelines
Quality of evidence is classified as high, The Ministry of Health of Saudi Arabia and
moderate, low, or very low based on McMaster University Practice Guidelines
decisions about methodological provide clinicians and their patients with a
characteristics of the available evidence for a basis for rational decisions about colorectal
specific health care problem. The definition of cancer screening. Clinicians, patients, third-
each category is as follows: party payers, institutional review committees,
other stakeholders, or the courts should never
High: We are very confident that the view these recommendations as dictates. As
true effect lies close to that of the described in other guidelines following the
estimate of the effect. GRADE approach, no guideline or
Moderate: We are moderately recommendation can take into account all of
confident in the effect estimate: The the often-compelling unique features of
true effect is likely to be close to the individual clinical circumstances. Therefore,
estimate of the effect, but there is a no one charged with evaluating clinicians
possibility that it is substantially actions should attempt to apply the
different. recommendations from these guidelines by
rote or in a blanket fashion.
Low: Our confidence in the effect
estimate is limited: The true effect
Statements about the underlying values and
may be substantially different from
preferences, resources, feasibility, equity,
the estimate of the effect.
acceptability as well as other qualifying
Very low: We have very little
remarks accompanying each recommendation
confidence in the effect estimate: The
are its integral parts and serve to facilitate an
true effect is likely to be substantially
accurate interpretation. They should never be
different from the estimate of effect.
omitted when quoting or translating
recommendations from these guidelines if
Grading of the strength of recommendations
they influence the strength or direction of the
The GRADE working group defines the
recommendation.
strength of recommendation as the extent to
which we can be confident that desirable
effects of an intervention outweigh Key questions
undesirable effects. According to the GRADE
approach, the strength of a recommendation
The following is a list of the clinical questions
is either strong or conditional (also known as
selected by the Saudi expert panel and
or called weak) and has explicit implications.4
addressed in this guideline.
Understanding the interpretation of these two
grades either strong or conditional (weak)
1. Should colorectal cancer (CRC)
of the strength of recommendations is
screening be used in asymptomatic
essential for sagacious clinical decision-
average risk population compared to
making (see Table 1).
no screening?
2. Should CRC screening be used in
As a quality measure for any practice
average risk population aged 70 years
guideline prior to publication, the final report
or older compared to no screening?
have been externally peer reviewed by a
Screening for colorectal cancer
7

3. Should colonoscopy be used for CRC that probably patients would have no
screening in asymptomatic average uncertainty about how they value CRC-related
risk population compared to no mortality, CRC-related incidence, and serious
screening? complications; however, the panel recognized
4. Should flexible sigmoidoscopy (FS) be some uncertainty based on the paucity of
used for CRC screening in evidence regarding patients preferences in
asymptomatic average risk population the Kingdom of Saudi Arabia.
compared to no screening?
5. Should CT colonography (CTC) be used Implementation Considerations and
for CRC screening in asymptomatic Monitoring
average risk population compared to Several items were mentioned by the panel
colonoscopy? for consideration during implementation of
6. Should FS be used for CRC screening these recommendations. Many addressed the
in average risk population compared need for capacity building at the population
to guaiac fecal occult blood testing level through strategies to increase
(gFOBT)? population-level awareness and knowledge of
7. Should FS be used for CRC screening endoscopic procedures and technology;
in average risk population compared monitoring and evaluation of
to colonoscopy? patients/clinicians acceptability and uptake
once the recommendations are implemented;
development of a database to capture
Recommendations screening results; implementation of
technology to provide screening reminders to
For each of the recommendations below we clinicians and patients (e.g., EMRs, mobile
describe the considerations and judgements phone, etc.); and implementation of quality
made by the panel on the available evidence indicators (KPIs) among endoscopists and
about the factors in the evidence-to-decision their peers to improve quality control.
framework (i.e. benefits and harms of the
options, resource use, feasibility, In order to improve consistency in screening
acceptability, balance of desirable and skills among endoscopists and to avoid
undesirable consequences, etc.). The evidence complications, education and certifications
and discussions on values and preferences, are needed for doctors, nurse endoscopists,
implementation considerations and and other clinical staff. Also training is needed
monitoring, and research priorities were for specialists on endoscopy (e.g., nurse
consistent throughout all recommendations endoscopists). Resources exist on current
and thus are summarized below. Additional accreditation of screening programs, including
considerations determined to apply to only guidelines released for screening
one recommendation are noted within that colonoscopists by the Joint Advisory Group on
section. GI Endoscopy10.

Values and Preferences Question 1: Should colorectal cancer (CRC)


The values and preferences of the patient, as screening be used in asymptomatic average
identified by the panel, were similar for all risk population compared to no screening?
recommendations in this document and
should be recognized throughout. The Summary of Findings:
patient-important outcomes identified in the The summary of evidence was based on the
nascent stages of the recommendations for compilation of three systematic reviews1,2,7.
each research question were all-cause The updated literature search did not identify
mortality or CRC-related mortality, CRC- any other studies for inclusion.
related incidence, and serious complications.
Given those outcomes, the panel determined Benefits of the Option:
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Pooled results from 8 randomized controlled


trials (total of 743,587 patients) of CRC Resource Use:
screening technologies, FS and FOBT, found No direct studies of cost utility were identified
high quality evidence for CRC-related for CRC screening in KSA; therefore, indirect
mortality (RR 0.80; 95% CI: 0.75 to 0.85; data from screening programs in other
absolute effect: 131 fewer events per countries in the Middle East was identified13,
100,000) and moderate quality evidence for as well as Gomes et al., examining
CRC-related incidence (RR 0.88; 95% CI: 0.80 colonoscopy and CTC screening only, which
to 0.96; absolute effect 199 fewer events per suggested cost-effectiveness for screening
100,000)1. technologies14.

Harms of the Option: Balance between desirable and undesirable


A meta-analysis of 6 observational studies consequences:
found moderate quality evidence, due to This question underwent two reviews at the
magnitude, of 0.01% more (16 request of the panel. A majority of the panel
events/126,985 procedures) serious during the second review agreed that instead
complications associated with FS compared of the "desirable consequences probably
with no screening intervention, such as outweigh the undesirable consequences" that
perforation, bleeding, and death (RR not based on the discussion and evidence
estimable; absolute effect: 34 more per identified while making recommendations 2
100,000)2. through 7, the "desirable consequences
clearly outweigh undesirable consequences";
Acceptability: however, it should be noted that while a
A cross-sectional study (a total of 500 majority agreed with "clearly outweigh" there
participants) was conducted in Riyadh to were some reservations remaining. As per
examine current knowledge and acceptability GRADE guidance, "clearly outweigh" makes
of CRC screening11. While the study identified this a strong recommendation.
some discrepancies in general knowledge, risk
factors, symptoms, and screening tests to The desirable consequences mainly centered
identify CRC, the majority of persons on earlier diagnosis allowing for more
interviewed (71%) reported willingness to effective treatment and better clinical
undergo CRC screening, which increased to outcomes. The undesirable consequences
83% if there was a family history of CRC11,12. included complications of screening, and the
Acceptability among patients increased when resources and costs associated with
screening was recommended by a physician. widespread implementation. Despite not
Among both women and men, CTC was having much context-specific evidence the
identified as the most preferred screening panel felt that there was enough
modality followed by stool-based test, consideration to suggest desirable
colonoscopy, and FS. FS was the least consequences clearly outweigh undesirable.
appreciated test by persons surveyed (15%).
The panel recognized that there is much
Feasibility: evidence that will come out on specific topics
While the panel determined that CRC related to CRC screening over the next few
screening was probably feasible to years, as mentioned in Research Priorities,
implement, this was recognizing that and an update of these guidelines should be a
infrastructure limitations exist in KSA such as priority as new evidence is published.
a shortage of physicians to implement Additionally, this recommendation was made
screening, trained clinical staff (nurse based on confidence in strong indirect
endoscopists), or mail delivery in some rural evidence, when direct evidence was not
areas (specifically for FOBT). Wait times are available; however, this can be re-evaluated if
currently long to receive screening. more direct evidence becomes available.
Screening for colorectal cancer
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Acceptability:
Recommendation 1: Its uncertain whether or not patients in this
age group would be accepting of CRC
The panel recommends using colorectal screening based on limited research among
cancer screening for asymptomatic, average patients in this age group and specifically in
risk persons rather than no screening. KSA.
(strong recommendation, low quality
evidence) Feasibility:
Screening persons aged 70 or older would
Remarks: probably be feasible to implement in KSA.
The panel agreed that they were
making the most informed decision Resource Use:
despite low quality of evidence and No direct studies of cost utility were identified
that future research would be for CRC screening in KSA; therefore, indirect
unlikely to change this data from screening programs in other
recommendation. countries in the Middle East was identified, as
well as Gomes et al., examining colonoscopy
and CTC screening only, which suggested cost-
Question 2: Should CRC screening be used in effectiveness for screening technologies13,14.
average risk population aged 70 years or
older compared to no screening? Higher complication rate of testing persons
aged 70 or older may lead to increased costs
Summary of Findings: of co-interventions. Additionally, based on
The summary of evidence was based on the country-level data, persons aged 70 and older
compilation of three systematic reviews1,2,7. make up a smaller subset of the population,
The updated literature search did not identify especially those who are asymptomatic and at
any other studies for inclusion. average risk for screening. Thus, due to the
smaller subset of population but still higher
Benefits of the Option: costs, the resources required for screening
Pooled results from 8 randomized controlled would not be small.
trials (total of 743,587 patients) of CRC
screening technologies, FS and FOBT, found Balance between desirable and undesirable
high quality evidence for CRC-related consequences:
mortality (RR 0.80; 95% CI: 0.75 to 0.85; Due to the expected reduced benefits
absolute effect: 131 fewer events per experienced by patients aged 70 and older
100,000) and moderate quality evidence for and increased risk in serious complications of
CRC-related incidence (RR 0.88; 95% CI: 0.80 some screening technologies, the undesirable
to 0.96; absolute effect 199 fewer events per consequences probably outweigh the
100,000)1,7. desirable consequences in most settings. This
is in contrast to screening in a younger patient
Harms of the Option: population where the desirable consequences
A meta-analysis of 6 observational studies are more clearly seen.
found moderate quality evidence, due to
magnitude, of 0.01% more (16
events/126,985 procedures) serious
complications associated with FS compared
with no screening intervention, such as
perforation, bleeding, and death (RR not Recommendation 2:
estimable; absolute effect: 34 more per
100,000)2. The panel suggests not using colorectal
cancer screening for asymptomatic persons
Screening for colorectal cancer
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at average risk aged 70 years or older. CRC-related mortality (RR 0.32; 95% CI: 0.23
(conditional recommendation, low quality to 0.43; absolute effect 190 fewer per
evidence) 100,000)7. A meta-analysis of 5 observational
studies found very low quality evidence, due
Remarks: to some concerns about risk of bias and
Consider that some individual inconsistency, for benefit of colonoscopy
patients might still benefit from screening over no screening for CRC-related
screening (if healthy, lack incidence (RR 0.31; 95% CI: 0.12 to 0.77;
comorbidities, and predicted survival absolute effect: 751 fewer per 100,000)7.
beyond 10 years at the time of
screening) Harms of the Option:
Consider additional resources A meta-analysis of 12 non-randomized studies
needed for mental health and social (a total of 57,742 participants) found low
support if cancer is identified and quality evidence of increased complications,
surgery or other treatment may not including perforations, hemorrhage,
be offered or appropriate diverticulitis, cardiovascular events, severe
abdominal pain, and death from colonoscopy
(RR not estimable; absolute effect 2.8 events
Implementation Considerations and per 1000, from 1.5 to 5.2 events per 1000)2.
Monitoring:
The panel identified additional considerations Acceptability:
for implementation of this recommendation. Colonoscopy was determined to probably be
Specifically among persons aged 70 and older, acceptable to patients; recognizing that there
assessments and provision of comprehensive is limited evidence on patients acceptability
support (e.g., social and mental health in KSA. A cross-sectional study (a total of 500
services) should be provided, if needed, if participants) was conducted in Riyadh to
patients are diagnosed and determined to not examine current knowledge and acceptability
be candidates for treatment. of CRC screening11. While the study identified
some discrepancies in general knowledge, risk
factors, symptoms, and screening tests to
Question 3: Should colonoscopy be used for identify CRC, the majority of persons
CRC screening in asymptomatic average risk interviewed (71%) reported willingness to
population compared to no screening? undergo CRC screening, which increased to
83% if there was a family history of CRC11,12.
Summary of Findings: Acceptability among patients increased when
A recent systematic review by Brenner et al. screening was recommended by a physician.
examining CRC screening using colonoscopy Among both women and men, CTC was
was identified7. As the search described in the identified as the most preferred screening
study extended through November 2013, an modality followed by stool-based test,
updated search from November 2013 through colonoscopy, and FS. FS was the least
November 2014 was conducted in PubMed. appreciated test by persons surveyed (15%).
No new eligible trials were identified for
inclusion when updating the evidence. Harms Feasibility:
data was collected from a recent USPSTF While the panel determined that CRC
report2. screening was probably feasible to
implement, this was recognizing that
infrastructure limitations exist in KSA such as,
Benefits of the Option: a shortage of physicians to implement
A meta-analysis of 3 observational studies screening and trained clinical staff (nurse
found low quality evidence for benefit of endoscopists). Wait times are currently long
colonoscopy screening over no screening for to receive colonoscopies.
Screening for colorectal cancer
11

asymptomatic, average risk population.


Resource Use: (strong recommendation, low quality
Indirect study of cost-effectiveness of CRC- evidence)
screening technologies in Iran suggest that
colonoscopies are cost effective, based on the Remarks:
cost per QALY threshold of 50,000 USD15,16. Colonoscopy is considered the
Additionally, results from a cost-feasibility gold standard and there is high
study of CRC-screening technologies in KSA confidence in the magnitude of the
provided data on the cost to the ministry. The association, even though that is
resources required to implement colonoscopy based on low quality evidence
instead of no screening would not be small; Some uncertainty is recognized
however, the incremental cost would given the indirect evidence
probably be small relative to the net benefits. regarding resources, values and
preference, health inequalities, and
Balance between desirable and undesirable feasibility
consequences:
Desirable consequences clearly outweigh the
undesirable consequences. Similar
considerations to the above Question 4: Should flexible sigmoidoscopy
recommendations. The benefits of screening, (FS) be used for CRC screening in
although lacking context-specific evidence, asymptomatic average risk population
were felt to be significant enough with compared to no screening?
colonoscopy that they outweigh any potential
undesirable consequences (e.g., Summary of Findings:
complications, costs, implementation A recent systematic review by Brenner et al.
barriers). This is especially true given (2014) examining CRC screening using FS was
colonoscopy represents the gold-standard for identified. As the search described in the
CRC screening and should have the lowest study extended through November 2013, an
amount of false positives and false negatives updated search from November 2013 through
compared to other tools. November 2014 was conducted in PubMed.
No new eligible trials were identified for
inclusion when updating the evidence. Harms
data was collected from a recent USPSTF
report (2008).

Benefits of the Option:


The meta-analysis of 4 trials (total of 413,945
participants) found high quality evidence that
FS reduces CRC-related mortality (RR 0.72;
95% CI: 0.65 to 0.80; absolute effect: 119
fewer per 100,000) and low quality evidence,
due to concerns with selection bias and
inconsistency, that FS reduces CRC-related
incidence (RR 0.82; 95% CI: 0.75 to 0.89;
absolute effect: 273 fewer per 100,000)7.

Recommendation 3: Harms of the Option:


A meta-analysis of 6 observational studies
The panel recommends screening found moderate quality evidence, due to
colonoscopy rather than no screening for magnitude, of 0.01% more (16
Screening for colorectal cancer
12

events/126,985 procedures) serious complications, cost and implementation


complications associated with FS compared barriers.
with no screening intervention, such as
perforation, bleeding, and death (RR not Recommendation 4:
estimable; absolute effect: 0.34 more per
100,000)2. The panel recommends using flexible
sigmoidoscopy (FS) for colorectal cancer
Acceptability: screening rather than no screening for
Flexible sigmoidoscopy was recognized as the asymptomatic persons at average risk.
least appreciated method for CRC screening (strong recommendation, moderate quality
based on a cross-sectional survey conducted evidence)
in Riyadh11,12; however, when compared with
no screening, implementation of FS would Remarks:
probably still be acceptable to patients and This recommendation refers to FS
other key stakeholders. screening every 5 years when
combined with annual fecal occult
Feasibility: blood (FOBT) or fecal
FS does not necessitate sedation, which immunochemical (FIT) testing or
increases feasibility and decreases cost. FS every 3 years without annual FIT
would probably be feasible to implement; testing
however, there is some uncertainty about the
current infrastructure (e.g., clinical training)
and resources in place for their widespread
use currently. Question 5: Should CT colonography (CTC) be
used for CRC screening in asymptomatic,
Resource Use: average risk population compared to
Indirect study of cost-effectiveness of CRC- colonoscopy?
screening technologies in Iran suggest that FS
are cost effective, based on the cost per QALY Summary of Findings:
threshold of 50,000 USD15,16. Additionally, Two systematic reviews were identified that
results from a cost-feasibility study of CRC- pooled the sensitivities and specificities of
screening technologies in KSA provided data each technology15,17. While Allameh et al.,
on the cost to the ministry. The resources presents pooled estimates for both CT
required to implement FS instead of no colonography and colonoscopy as a result of a
screening would not be small; however, the comprehensive literature review, the quality
incremental cost would probably be small of the evidence regarding the included studies
relative to the net benefits. and patient population raises concerns
regarding directness15. De Haan et al., pool
Balance between desirable and undesirable results from five studies examining CT
consequences: colonography diagnostic accuracy against
Based on the evidence reviewed, the colonography among patients undergoing
desirable consequences of offering FS versus both procedures in the same day17.
no screening clearly outweighed the Specifically, de Haan et al. include studies
undesirable consequences in most settings. using both technologies among asymptomatic
The benefit of FS is less clear compared to persons at average risk. The systematic review
that of colonoscopy as FS fails to rule out was updated through December 2014,
right-sided malignancy. That being said, the identifying two additional studies18,19. While
benefits of screening using FS were still felt to these studies were not pooled with the results
clearly outweigh any undesirable from de Haan, they were consistent in their
consequences such as procedure reported effect.
Screening for colorectal cancer
13

Benefits of the Option: implement, this was recognizing that


While the evidence suggested greater infrastructure limitations exist in KSA such as,
sensitivity and specificity with screening a shortage of physicians to implement
colonoscopy, the panel highlighted that in the screening and trained clinical staff (nurse
context of the KSA, CT colonography can be endoscopists). Wait times are currently long
more feasible with shorter wait times given to receive colonoscopies and some patients
the limited endoscopic resources. are referred to CT colonography as an
alternative option.
Harms of the Option:
A meta-analysis of 4 non-randomized studies Resource Use:
(a total of 4018 participants) found low Indirect research from Gomes et al.,
quality evidence of the sensitivity and compared CT colonography with colonoscopy
specificity of CT colonography compared to in Britain and found CT colonography to be
colonoscopy (Sensitivity 0.83; 95% CI 0.74 to more cost effective14.
0.89; Specificity 0.91; 95% CI 0.84 to 0.96;
True positives: 13 fewer events with CT Balance between desirable and undesirable
colonography; True negatives: 76 fewer consequences:
events with CT colonography)17. A meta- Based on the evidence reviewed, the panel
analysis of 12 non-randomized studies (a total determined the desirable consequences and
of 57,742 participants) found low quality undesirable consequences of offering CT
evidence of increased complications, including colonography versus colonoscopy were
perforations, hemorrhage, diverticulitis, similar in most settings. The benefit of CT
cardiovascular events, severe abdominal pain, colonography is less clear compared to that of
and death from colonoscopy (RR not colonoscopy, as CT colonography requires
estimable; absolute effect 2.8 events per similar bowel preparation and confirmatory
1000, from 1.5 to 5.2 events per 1000)2. Few screening using colonoscopy. That being said,
serious complications have been reported for given the availability of trained clinical staff
CT colonography2. Low complications and and endoscopic resources in the KSA,
burden from CTC; however, discomfort from sometimes CT colonography wait times are
bowel preparation is the same for CTC and shorter.
colonoscopy. Additional harms to consider
include radiation exposure.

Acceptability:
Colonoscopy and CT colonography were
determined to probably be acceptable to
patients; recognizing that there is limited
evidence on patients acceptability in KSA. A
cross-sectional study was conducted in Riyadh
to examine acceptability of CRC screening.
The majority of persons interviewed reported
willingness to undergo CRC screening,
preferring CT colonography over
colonoscopy11,12. Acceptability among patients
increases when screening is recommended by
a physician.

Feasibility: Recommendation 5:
While the panel determined that CRC
screening was probably feasible to The panel suggests using colonoscopy rather
Screening for colorectal cancer
14

than CT colonography for diagnosis of blood testing (gFOBT)?


asymptomatic, average risk patients.
(conditional recommendation, low quality Summary of Findings:
evidence) A recent systematic review by Brenner et al.
examining CRC screening using FS was
Remarks: identified7. As the search described in the
The decision to use colonoscopy study extended through November 2013, an
instead of CT colonography should updated search from November 2013 through
be driven by feasibility and November 2014 was conducted in PubMed.
availability of the tests, as No new eligible trials were identified for
sometimes the wait for endoscopy inclusion when updating the evidence. Harms
services is too long for data was collected from a recent USPSTF
asymptomatic patient screening report 2.
For patients preferring non-invasive
screening, they may choose to A Cochrane systematic review examined the
undergo CT colonography initially effectiveness of screening for colorectal
with the understanding they would cancer with flexible sigmoidoscopy vs. faecal
still be subjected to the bowel occult blood testing (FOBT)1. Results from
preparation procedure and that CT RCTs of flexible sigmoidoscopy vs. no
colonography still has small risks of screening and FOBT vs. no screening were
complications and the risk of presented; however, no indirect comparison
radiation exposure was conducted. Based on an assessment of
the individual studies comparing FS to no
screening, identified the studies in Brenner et
Implementation Considerations and al. as providing better quality evidence for this
Monitoring: research question7. A literature search was
The panel identified additional considerations conducted to update the results of the review,
for implementation of this recommendation. up to November 2014, but identified no other
During implementation, given the resource studies meeting inclusion or exclusion criteria
constraints identified, consideration should be to include in an updated pooled analysis.
given to the availability of endoscopy services
and the need for more frequent screening if Separate evidence profiles of screening using
using CT colonography (5 years) vs. flexible sigmoidoscopy vs. no screening and
colonoscopy (10 years). Regarding education, screening using FOBT vs. no screening are
emphasis should be placed on the guidelines presented.
for conducting and reading the results from
the CT colonography, including training and Benefits of the Option:
certification for radiologists. Training and A meta-analysis of 4 trials (total of 413,945
certifications should be tracked, as well as all participants) found high quality evidence that
serious complications experienced by patients FS reduces CRC-related mortality (RR 0.72;
undergoing CT colonography, including 95% CI: 0.65 to 0.80; absolute effect: 119
radiation exposure. fewer per 100,000) and low quality evidence,
due to concerns with selection bias and
inconsistency, that FS reduces CRC-related
incidence (RR 0.82; 95% CI: 0.75 to 0.89;
absolute effect: 273 fewer per 100,000)7. A
meta-analysis of 4 trials (a total of 329,642
participants) found moderate quality evidence
Question 6: Should flexible sigmoidoscopy of gFOBT reducing all-cause mortality (OR
(FS) be used for CRC screening in average risk 0.84; 95% CI 0.78 to 0.90; absolute effect 161
population compared to guaiac fecal occult fewer events per 100,000). The same meta-
Screening for colorectal cancer
15

analysis found low quality evidence that analysis conducted in Iran, both screening
gFOBT was not significantly associated with a technologies were determined to be cost
reduction in colorectal cancer incidence (RR effective based on the $50,000 cost per
0.93; 95% CI 0.84 to 1.04; absolute effect 132 QALY15,16.
fewer events per 100,000)1.
Balance between desirable and undesirable
Harms of the Option: consequences:
A meta-analysis of 6 observational studies The panel highlighted the current practices in
found moderate quality evidence, due to KSA, which are that gFOBT is typically not
magnitude, of 0.01% more (16 performed for colorectal screening and less
events/126,985 procedures) serious feasible to implement because of access to
complications associated with FS compared postal services, and FS is typically not
with no screening intervention, such as performed without a stool-based screening
perforation, bleeding, and death (RR not test; therefore the balance between desirable
estimable; absolute effect: 0.34 more per and undesirable consequences for these two
100,000)2. No serious complications have methods is uncertain. That being said, given
been reported from studies examining the benefit of screening using FS, as well as
screening with gFOBT or other fecal colorectal the acceptability and feasibility, the panel
cancer screening tests2. would suggest this over gFOBT, with the
caveat that the stool-based fecal
Acceptability: immunochemistry test (FIT) be used at annual
FS and gFOBT were determined to probably intervals in combination with FS every five
be acceptable to patients; recognizing that years.
there is limited evidence on patients
acceptability in KSA. A cross-sectional study Recommendation 6:
was conducted in Riyadh to examine
acceptability of CRC screening. The majority of The panel suggests offering flexible
persons interviewed reported willingness to sigmoidoscopy rather than guaiac fecal
undergo CRC screening, preferring a stool- occult blood test (gFOBT) for colorectal
based test over FS11,12. Acceptability among cancer screening among asymptomatic,
patients increases when screening is average risk persons in the Kingdom of Saudi
recommended by a physician. Arabia. (conditional recommendation, very
low quality evidence)
Feasibility:
FS does not necessitate sedation, which Remarks:
increases feasibility and decreases cost. FS gFOBT is a less sensitive method, but
would probably be feasible to implement; depending on the availability of other
however, there is some uncertainty about the screening modalities, setting, and
current infrastructure (e.g., clinical training) resources it can still be used
and resources in place for their widespread FS is often done in combination with
use currently. gFOBT requires receipt of mail FOBT or FIT testing to ensure the
or access to a physicians office or clinic, entire colon is screened
which is not always available.

Resource Use:
The panel was uncertain about the balance of
resource use for FS versus gFOBT. Cost
considerations included higher indirect and
direct costs to perform FS every 3 to 5 years, Question 7: Should FS be used for CRC
as well as the cost to mail gFOBT to citizens screening in average risk population
every year. Based on an indirect cost-utility compared to colonoscopy?
Screening for colorectal cancer
16

and death from colonoscopy (RR not


Summary of Findings: estimable; absolute effect 2.8 events per
A recent systematic review by Brenner et al. 1000, from 1.5 to 5.2 events per 1000)2.
examining CRC screening using both
colonoscopy and FS was identified7. As the Acceptability:
search described in the study extended Colonoscopy and FS were determined to
through November 2013, an updated search probably be acceptable to patients;
from November 2013 through November recognizing that there is limited evidence on
2014 was conducted in PubMed. No new patients acceptability in KSA. A cross-
eligible trials were identified for inclusion sectional study was conducted in Riyadh to
when updating the evidence. Harms data was examine acceptability of CRC screening11. The
collected from a recent USPSTF report2. majority of persons interviewed reported
willingness to undergo CRC screening,
Benefits of the Option: preferring colonoscopy over FS11,12.
A meta-analysis of 4 trials (total of 413,945 Acceptability among patients increases when
participants) found high quality evidence that screening is recommended by a physician.
FS reduces CRC-related mortality (RR 0.72;
95% CI: 0.65 to 0.80; absolute effect: 119 Feasibility:
fewer per 100,000) and low quality evidence, FS does not necessitate sedation, which
due to concerns with selection bias and increases feasibility and decreases cost. FS
inconsistency, that FS reduces CRC-related would probably be feasible to implement;
incidence (RR 0.82; 95% CI: 0.75 to 0.89; however, there is some uncertainty about the
absolute effect: 273 fewer per 100,000)7. A current infrastructure (e.g., clinical training)
meta-analysis of 3 observational studies and resources in place for their widespread
found low quality evidence for benefit of use currently. While the panel determined
colonoscopy screening over no screening for that CRC screening was probably feasible to
CRC-related mortality (RR 0.32; 95% CI: 0.23 implement, this was recognizing that
to 0.43; absolute effect 190 fewer per infrastructure limitations exist in KSA such as,
100,000)7. A meta-analysis of 5 observational a shortage of physicians to implement
studies found very low quality evidence, due screening and trained clinical staff (nurse
to some concerns about risk of bias and endoscopists). Wait times are currently long
inconsistency, for benefit of colonoscopy to receive colonoscopies.
screening over no screening for CRC-related
incidence (RR 0.31; 95% CI: 0.12 to 0.77; Resource Use:
absolute effect: 751 fewer per 100,000)7. Indirect study of cost-effectiveness of CRC-
screening technologies in Iran suggest that
Harms of the Option: colonoscopies and FS are cost effective, based
A meta-analysis of 6 observational studies on the cost per QALY threshold of 50,000
found moderate quality evidence, due to USD15,16. Additionally, results from a cost-
magnitude, of 0.01% more (16 feasibility study of CRC-screening technologies
events/126,985 procedures) serious in KSA provided data on the cost to the
complications associated with FS compared ministry. The resources required to
with no screening intervention, such as implement colonoscopy or FS would not be
perforation, bleeding, and death (RR not small and the incremental cost if comparing
estimable; absolute effect: 0.34 more per FS to colonoscopy would probably not be
100,000)7. A meta-analysis of 12 non- small relative to the net benefits.
randomized studies (a total of 57,742
participants) found low quality evidence of Balance between desirable and undesirable
increased complications, including consequences:
perforations, hemorrhage, diverticulitis, The panel determined that while many factors
cardiovascular events, severe abdominal pain, are similar between the two methods,
Screening for colorectal cancer
17

patients would value the reduced screening The panel identified several priorities for
frequency and confirmatory results of future research based on these
colonoscopy more versus FS, given the close recommendations, including
balance between the benefits and harms, and Population-level study to identify the
resource requirements. The panel recognized incidence of polyps and other pre-
that due to the indirect evidence and other cancerous adenomas detected during
factors introducing uncertainty, that some CRC screening by colonoscopy and FS;
patients would prefer colonoscopy; however, Population-level study to identify the
some would not. incidence of serious complications
experienced by patients during CRC
Recommendation 7: screening using colonoscopy, FS, and
CTC;
The panel suggests offering colonoscopy Evaluation of potential health
rather than flexible sigmoidoscopy for inequalities and differences in access
colorectal cancer screening among to care among populations (e.g.,
asymptomatic, average risk persons. urban vs. rural, male vs. female, etc.)
(conditional recommendation, low quality as a result of the implementation of
evidence) these recommendations;
Primary and secondary research to
Remarks: determine at which age to initiate CRC
FS needs to be done at least twice as screening in KSA.
often (every 3-to-5 years depending
on whether FIT provided annually) In addition, several head-to-head studies or
Consider that FS misses right-sided evidence reviews comparing the following
disease CRC screening tests were identified to inform
Benefit of FS may be more if the next iteration of these guidelines:
combined with FOBT or FIT Combination FIT/FS versus
colonoscopy
Use of FIT versus no screening
Use of FIT versus C-scope for
screening
DNA testing versus no screening
DNA testing versus colonoscopy
DNA testing versus FIT

Research Priorities
Screening for colorectal cancer
18

References
1. Holme O, Bretthauer M, Fretheim A, Odgaard-Jensen J, Hoff G. Flexible sigmoidoscopy
versus faecal occult blood testing for colorectal cancer screening in asymptomatic individuals. The
Cochrane database of systematic reviews 2013;9:CD009259.
2. Force USPST. Screening for colorectal cancer: U.S. Preventive Services Task Force
recommendation statement. Annals of internal medicine 2008;149:627-37.
3. Guyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging consensus on rating quality of
evidence and strength of recommendations. Bmj 2008;336:924-6.
4. WHO Handbook for Guideline Development. World Health Organization, 2012. (Accessed
February 7, 2014, at http://apps.who.int/iris/bitstream/10665/75146/1/9789241548441_eng.pdf.)
5. Balshem H, Helfand M, Schunemann HJ, et al. GRADE guidelines: 3. Rating the quality of
evidence. Journal of clinical epidemiology 2011;64:401-6.
6. Andrews J, Guyatt G, Oxman AD, et al. GRADE guidelines: 14. Going from evidence to
recommendations: the significance and presentation of recommendations. Journal of clinical
epidemiology 2013;66:719-25.
7. Brenner H, Stock C, Hoffmeister M. Effect of screening sigmoidoscopy and screening
colonoscopy on colorectal cancer incidence and mortality: systematic review and meta-analysis of
randomised controlled trials and observational studies. Bmj 2014;348:g2467.
8. Health KoSAMo. Cancer Incidence Report Saudi Arabia 2010. 2014.
9. Guyatt G, Oxman AD, Akl EA, et al. GRADE guidelines: 1. Introduction-GRADE evidence
profiles and summary of findings tables. Journal of clinical epidemiology 2011;64:383-94.
10. Programme JOobotBCS. Accreditation of Screening Colonoscopists. Royal College of
Physicians 2013.
11. Almadi MA MM, Bohlega MS, Essa MA, AlDohan MS, Alabdallatif TA, AlSagri TY, Algahtani
FA, Mandil A. Effect of public knowledge, attitudes, and behavior on willingness to undergo
colorectal cancer screening using the health belief model. . Under review 2014.
12. Almadi MA, Alharbi, O., Azzam, N., Wadera, J., Sadaf, N., & Aljebreen, A. M. . Prevalence and
characteristics of colonic polyps and adenomas in 2654 colonoscopies in Saudi Arabia. Saudi Journal
of Gastroenterology 2014;20:154.
13. Barouni M, Larizadeh MH, Sabermahani A, Ghaderi H. Markov's modeling for screening
strategies for colorectal cancer. Asian Pacific journal of cancer prevention : APJCP 2012;13:5125-9.
14. Gomes M, Aldridge RW, Wylie P, Bell J, Epstein O. Cost-effectiveness analysis of 3-D
computerized tomography colonography versus optical colonoscopy for imaging symptomatic
gastroenterology patients. Applied health economics and health policy 2013;11:107-17.
15. Allameh Z, Davari M, Emami MH. Cost-effectiveness analysis of colorectal cancer screening
methods in Iran. Archives of Iranian medicine 2011;14:110-4.
16. Barouni M, Ghaderi H, Shahmoradi MK. The economic evaluation of screening for colorectal
cancer: Case of Iran. Clinical laboratory 2013;59:667-74.
17. de Haan MC, van Gelder, R. E., Graser, A., Bipat, S., & Stoker, J. Diagnostic value of CT-
colonography as compared to colonoscopy in an asymptomatic screening population: a meta-
analysis. European radiology 2011;21:1747-63.
18. Lefere P, Silva C, Gryspeerdt S, et al. Teleradiology based CT colonography to screen a
population group of a remote island; at average risk for colorectal cancer. European journal of
radiology 2013;82:e262-7.
19. Stoop EM, de Haan MC, de Wijkerslooth TR, et al. Participation and yield of colonoscopy
versus non-cathartic CT colonography in population-based screening for colorectal cancer: a
randomised controlled trial. The Lancet Oncology 2012;13:55-64.
20. Mosli MH, Al-Ahwal MS. Colorectal cancer in the Kingdom of Saudi Arabia: need for
screening. Asian Pacific Journal of Cancer Prevention 2012;13:3809-13.
Screening for colorectal cancer
19

21. Khayyat YM, Ibrahim EM. Public awareness of colon cancer screening among the general
population: A study from the Western Region of Saudi Arabia. Qatar medical journal 2014;2014:17.
22. Azaiza F, Cohen M. Colorectal cancer screening, intentions, and predictors in Jewish and
Arab Israelis: a population-based study. Health education & behavior : the official publication of the
Society for Public Health Education 2008;35:478-93.
23. Gulten G, Memnun S, Ayse K, Aygul A, Gulcin A. Breast, cervical, and colorectal cancer
screening status of a group of Turkish women. Asian Pacific journal of cancer prevention : APJCP
2012;13:4273-9.
24. Qumseya BJ, Tayem YI, Dasa OY, et al. Barriers to colorectal cancer screening in Palestine: a
national study in a medically underserved population. Clinical gastroenterology and hepatology : the
official clinical practice journal of the American Gastroenterological Association 2014;12:463-9.
25. Aljebreen AM, Almadi, M. A., & Leung, F. W. . Sedated vs unsedated colonoscopy: A
prospective study. World Journal of Gastroenterology 2014;20:5113-8.
26. Ries LAG, Young Jr JL, Keel GE, Eisner MP, Lin YD, Horner M-JD. Cancer survival among
adults: US SEER program, 1988-2001. Patient and tumor characteristics Bethesda, MD: US
Department of Health and Human Services, National Institutes of Health, National Cancer Institute
2007.
27. Bellini D, Rengo M, De Cecco CN, Iafrate F, Hassan C, Laghi A. Perforation rate in CT
colonography: a systematic review of the literature and meta-analysis. European radiology
2014;24:1487-96.
Screening for colorectal cancer
20

Appendices
1. Appendix 1: Evidence-to-Decision Tables
2. Appendix 2: Search Strategies and Results
Screening for colorectal cancer
21

Appendix 1: Evidence to Decision Tables

Guideline Question 1: Should colorectal cancer (CRC) screening be used in asymptomatic average risk population compared to no
screening?

Problem: Screening for colorectal cancer Background and Objective: Colorectal cancer accounts for 10.4% of all newly diagnosed cases of cancer in Saudi
Option: CRC Screening Arabia, second overall only to breast cancer. However, it is not clear if the available evidence support country-wide
Comparison: No Screening CRC screening in asymptomatic, average risk patients to help detect and prevent cancer. We aim here to address the
Setting: Outpatient in KSA above question as a part of developing clinical practice guidelines on colorectal cancer in Saudi Arabia.
Perspective: Average risk population in Saudi
Arabia

Criteria Judgments Research evidence Additional considerations

In Saudi Arabia, the 2010 cancer registry reported that 10.4% of cases Possible underestimation of CRC
of colorectal cancer. This is the predominant cancer detected among prevalence in communities in
No males and the third among females. 2009 Cancer Registry reports Saudi Arabia.
Probably baseline risk of CRC in 15/1000 persons in Saudi Arabia8.
no More confidence that this is a
Is there a Uncertain In 2005, of persons living in Saudi Arabia, approximately 38% did not priority problem because of the
identify at native Saudis20. The 2010 cancer registry also reported on consistency in incidence trend.
Problem problem
priority?
Probably the prevalence of colorectal cancer among the non-Saudi population,
yes living in Saudi Arabia. Of 3,265 cancer cases reported in 201, 11.6% This research question was assessed
twice by the KSA Expert Panel in light
Yes were identified as colorectal, second reported overall to breast cancer.
Among males and females, CRC ranked first among men (14.1%) and
of new evidence presented during the
Varies second among women (8.7%).
guideline development session. Any
changes from the original decisions
have been noted and rationale
Generally low awareness about recommended CRC screening, especially provided.
among persons with lower education21.

The relative importance or values of the main outcomes of interest: USPSTF reports that persons
Benefits & What is the No undergoing colonoscopy experience
harms of overall certainty included
the options of this evidence? studies 2.8 higher (1.5 to 5.2) risk difference
Screening for colorectal cancer
22

Criteria Judgments Research evidence Additional considerations

in complications than those not


Very low Relative
Certainty of
undergoing colonoscopy. Serious
Outcome the evidence
Low importance
(GRADE) complications are defined as
perforations, hemorrhage,
Moderate diverticulitis, cardiovascular
High Colorectal cancer-related mortality CRITICAL
events, severe abdominal pain,
HIGH and death (USPSTF 2008).
Indirect evidence provided,
Important examining studies of flexible
uncertainty
Colorectal cancer-related incidence CRITICAL
sigmoidoscopy pooled.
or variability MODERATE
Possibly Initially, the KSA expert panel
important said that the desirable anticipated
Serious complications of Flexible
uncertainty effects were probably large given
Sigmoidoscopy (including perforations,
CRITICAL

Is there or variability
hemorrhage, diverticulitis, cardiovascular doubts concerning application of
important LOW
uncertainty Probably events, severe abdominal pain, and death) data to KSA; however, when
examining individual data for FS
about how much no important
and colonoscopy became more
people value the uncertainty
main outcomes? of variability clear the benefits of CRC
Summary of findings: CRC screening compared to No screening in
screening.
No asymptomatic, average risk population in Saudi Arabia
important Relative Initially to address "Are the
Without
uncertainty With CRC Difference effect desirable effects large relative to
Outcome CRC
of variability screening (95% CI) (RR)
screening undesirable effects?" the KSA
(95% CI)
No known Expert Panel was split with a vote
undesirable of 5 for "Yes" and 4 for "Probably
523 per 131 fewer per Yes". During the second review, a
RR 0.80
No Colorectal cancer-
related mortality
654 per
100000
100000
(491 to
100000 (from
98 fewer to
(0.75 to
vote was not needed and overall
consensus given the evidence
0.85)
Probably 556) 164 fewer) review was for "Yes."
Are the no
desirable
anticipated Uncertain 1462 per 199 fewer per
RR 0.88
Colorectal cancer- 1661 per 100000 100000 (from
effects large?
Probably related incidence 100000 (1329 to 66 fewer to
(0.80 to
yes 0.96)
1595) 332 fewer)
Yes
Screening for colorectal cancer
23

Criteria Judgments Research evidence Additional considerations

Varies Serious complications


of Flexible
Sigmoidoscopy
No (including perforations,
0 per
0 per
34 more per
100000 (from not
Probably hemorrhage,
diverticulitis,
100000
100000
(0 to 0)
0.06 more to estimable
no 1.9 fewer)
cardiovascular events,
Are the
undesirable Uncertain severe abdominal pain,
and death)
anticipated
effects small?
Probably
yes

Yes
Varies
No
Probably
Are the no
desirable effects
large relative to
Uncertain
undesirable Probably
effects? yes

Yes
Varies
Minimal to no cost to patients
No living in KSA, both Saudi
nationals and expatriates, as
Probably either the government or
Are the no
Resource employer pays for necessary
use
resources
required small?
Uncertain health care.
Probably
yes Lower expense experienced in the
private sector vs public sector.
Yes
Screening for colorectal cancer
24

Criteria Judgments Research evidence Additional considerations

Varies
Incremental cost-effectiveness ratio (ICER) for colonoscopy in Iran A cost-feasibility report was sent
No estimated to be $8,700 per QALY13. CRC screening falls well below the forward to the ministry examining
Probably 50,000 ICER (generally acceptable willingness to pay threshold), and costs for different CRC screening
technologies, age groups, and
no below the GDP per Capita for Saudi Arabia ($25,851). Based on cost-
Is the lifetime. This data remains
utility analyses, colonoscopies every 10 years are recommended15,16.
incremental cost Uncertain unpublished; however, helped to
provide relative costs for
small relative to
the net benefits? Probably consideration throughout the
yes recommendation process.

Yes
Varies
Government-level recommendation would increase awareness of Variability existed in the KSA
screening recommendation. Panel concerning how a
recommendation for CRC
Increased Physicians recommendation and understanding of the benefit of screening would impact health
Probably screening are associated with intention to be screening22. inequalities. Topics considered
included: Possibly more health
increased
inequalities if using FOBT because
What would be Uncertain Having heard of CRC screening, higher education, and knowledge of
literacy to read and follow
the impact on screening benefits associated with increased intention to receive CRC
Equity
health Probably screening among Turkish women23.
instructions is necessary; persons
living in rural areas may have
inequities? reduced
less access to medical care than
Reduced Almadi et al.11 identified that access to and barriers of CRC screening persons in urban settings.
differ between ethnic groups and communities; however, there is
Varies limited information as to the extent that a mass screening
recommendation would have on health inequalities.
Indirect evidence discussed was
access to vaccinations when those
were implemented.
Screening for colorectal cancer
25

Criteria Judgments Research evidence Additional considerations

Decreased odds of receipt of colonoscopy independently associated with Low acceptability of screening
No lack of familiarity with CRC screening, distrust in Western medicine, and technologies by patients;
Probably embarrassment24 however, acceptability increases
no if recommended by a physician.
Is the option
Acceptability
acceptable to Uncertain Studies examining acceptability of repeat screening based on whether
sedated or not sedated for the procedure (i.e., colonoscopy) report no
key
stakeholders?
Probably significant difference25.
yes

Yes A cross-sectional study was conducted in Riyadh to examine


acceptability of CRC screening. The majority of persons interviewed
Varies reported willingness to undergo CRC screening11.

Some barriers have been identified to acceptance and uptake of CRC Infrastructure limitations exist in
screening, based on a cross-sectional study conducted in Riyadh. KSA such as, a shortage of
Barriers include lack of knowledge about screening; inaccessibility of physicians to implement
physicians, settings, and organizations conducting the screening; access screening, trained clinical staff
No to the health care delivery system, lack of time for those intended to be (nurse endoscopists), or mail
screened, transportation, financial barriers as well as fear from delivery in some rural areas
Probably receiving unwanted result as well as embarrassment or shame11. (specifically for FOBT). Wait times
no are currently long to receive

Feasibility
Is the option
feasible to
Uncertain screening.

implement? Probably Implementation is different than


yes
acceptability.
Yes
Varies "Probably Yes" was the overall
consensus; however, concerns
noted about uncertainty around
feasibility and the need for
additional research.
Screening for colorectal cancer
26

Recommendation
Should CRC screening vs. No screening be used in asymptomatic, average risk population in Saudi Arabia?
Undesirable consequences Undesirable consequences The balance between Desirable consequences Desirable consequences
Balance of clearly outweigh desirable probably outweigh desirable desirable and undesirable probably outweigh clearly outweigh undesirable
consequences consequences in most consequences in most consequences is closely undesirable consequences in consequences in most
settings settings balanced or uncertain most settings settings


Type of We recommend against offering this We suggest not offering this We suggest offering this
We recommend offering this option
recommendation option option option


The panel recommends using colorectal cancer screening for asymptomatic, average risk persons rather than no screening (strong
recommendation; low quality evidence)
Recommendation
Remarks:
- The panel agreed that they were making the most informed decision despite low quality of evidence and that future research would be unlikely
to change this recommendation

This question underwent two reviews at the request of the panel. A majority of the panel during the second review agreed that instead of the
"desirable consequences probably outweigh the undesirable consequences" that based on additional discussion and evidence, the "desirable
consequences clearly outweigh undesirable consequences"; however, it should be noted that while a majority agreed with "clearly outweigh"
there were some reservations remaining. As per GRADE guidance, "clearly outweigh" makes this a strong recommendation.
The desirable consequences mainly centered on earlier diagnosis allowing for more effective treatment and better clinical outcomes. The
undesirable consequences included complications of screening, and the resources and costs associated with widespread implementation. Despite
Justification
not having much context-specific evidence the panel felt that there was enough consideration to suggest desirable consequences clearly
outweigh undesirable.
Recognize that there is much evidence that will come out in the next few years, and an update of these guidelines should be a priority as new
evidence is published. Additionally, this recommendation was made based on confidence in strong indirect evidence, when direct evidence was
not available; however, this should be re-evaluated as more direct evidence becomes available.
A lot of discussion was concerning the difference between "probably outweigh" or "clearly outweigh" among the panelists.
Subgroup
considerations
Perhaps earlier age limit around 45 needed for Saudi inhabitants.
Screening for colorectal cancer
27

- Increase general awareness and knowledge of endoscopic procedures and technology


Implementation
considerations
- Education and certifications needed for doctors, nurse endoscopists, and other clinical staff
- Training of specialists on endoscopy (nurse endoscopists).

Database to capture screening results.


Monitoring and
evaluation
Implementation of technology to provide screening reminders to clinicians and patients (e.g., EMRs, mobile phone, etc.).
Quality indicators (KPIs) should be implemented among endoscopists and their peers to improve quality control.

- Conduct monitoring and evaluation of patients/clinicians acceptability and uptake once recommendations implemented
- Prevalence studies of polyp detection using colonoscopy and serious complications experienced by patients
Research
possibilities
- Assess the performance of colonoscopy in KSA
- Evaluation of access to care among different population groups (e.g., urban/rural, etc.)
- Age at which to initiate screening
Screening for colorectal cancer
28

Summary of Findings: Should colorectal cancer (CRC) screening be used in asymptomatic average risk population compared to no screening?
CRC screening compared to no screening in asymptomatic, average risk population aged 70 years or older in Saudi Arabia

Bibliography (systematic reviews): Brenner H, Stock C, Hoffmeister M. Effect of screening sigmoidoscopy and screening colonoscopy on colorectal cancer incidence and mortality: systematic review and meta-analysis of
randomised controlled trials and observational studies. BMJ. 2014;348:g2467. Hewitson, P., Glasziou, P., Watson, E., Towler, B., & Irwig, L. (2008). Cochrane systematic review of colorectal cancer screening using the fecal
occult blood test (hemoccult): an update. The American journal of gastroenterology, 103(6), 1541-1549. Whitlock, E. P., Lin, J. S., Liles, E., Beil, T. L., & Fu, R. (2008). Screening for colorectal cancer: a targeted, updated
systematic review for the US Preventive Services Task Force. Annals of Internal Medicine, 149(9), 638-658.

Outcomes of participants Quality of the Relative Anticipated absolute effects


(studies) evidence effect
Follow-up (GRADE) (95% CI) Risk with no Risk difference with CRC
screening screening

Colorectal cancer-related mortality (CRC Mortality) 743587 RR 0.80 Study population


(8 RCTs) 1
HIGH (0.75 to 0.85)
654 per 100000 131 fewer per 100000
(164 fewer to 98 fewer)
Colorectal cancer-related incidence (CRC incidence) 743587 RR 0.88 Study population
(8 RCTs) 1
MODERATE 2 (0.80 to 0.96)
1661 per 100000 199 fewer per 100000
(332 fewer to 66 fewer)
Serious complications of Flexible Sigmoidoscopy (including perforations, hemorrhage, diverticulitis, 126985 not estimable Study population
cardiovascular events, severe abdominal pain, and death) (Serious complications (FS)) (6 observational LOW 34
studies) 0 per 100000 0 fewer per 100000
(0 fewer to 0 fewer)

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio; OR: Odds ratio;

GRADE Working Group grades of evidence


High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
1. We combined the results of RCTs examining the effect of flexible sigmoidoscopy (4 RCTs) and FOBT (4 RCTs) compared to no screening.
2. I squared = 82%, we lowered by one point because the analysis combined two different interventions with likely different treatment effect, heterogeneity was reduced when trials for each intervention analyzed separately
3. Test for heterogeneity, P= 0.26
4. Although the event rate is low, we did not downgrade for imprecision, because the sample size was large, it appears to an extremely rare event.
5. These estimates are obtained from a pooled estimate across 6 observational studies comparing flexible sigmoidoscopy to no screening.
Screening for colorectal cancer
29

Guideline Question 2: Should CRC screening be used in average risk population aged 70 years or older compared to no screening?

Problem: Screening for colorectal cancer Background and Objective: Colorectal cancer accounts for 10.4% of all newly diagnosed cases of cancer in Saudi
Option: CRC Screening Arabia, second overall only to breast cancer. However, it is not clear if the available evidence support country-wide
Comparison: No Screening CRC screening among asymptomatic, average risk patients aged 70 years or older to help detect and prevent cancer.
Setting: Outpatient in KSA We aim here to address the above question as a part of developing clinical practice guidelines on colorectal cancer in
Perspective: Average risk population in Saudi Saudi Arabia.
Arabia

Criteria Judgments Research evidence Additional considerations

In Saudi Arabia, the 2010 cancer registry reported that 10.4% of cases Possible underestimation of CRC
of colorectal cancer. This is the predominant cancer detected among prevalence in communities in
males and the third among females. 2009 Cancer Registry reports Saudi Arabia.
baseline risk of CRC in 15/1000 persons in Saudi Arabia8.
More confidence that this is a
No In 2005, of persons living in Saudi Arabia, approximately 38% did not
identify at native Saudis20. The 2010 cancer registry also reported on
priority problem because of the
consistency in incidence trend.
Probably the prevalence of colorectal cancer among the non-Saudi population,
no living in Saudi Arabia. Of 3,265 cancer cases reported in 201, 11.6% This research question was assessed
were identified as colorectal, second reported overall to breast cancer. twice by the KSA Expert Panel in light
Is there a Uncertain Among males and females, CRC ranked first among men (14.1%) and
of new evidence presented during the
Problem problem guideline development session. Any
priority? Probably second among women (8.7%). changes from the original decisions
yes have been noted and rationale
Generally low awareness about recommended CRC screening, especially
Yes among persons with lower education21.
provided.

Varies Life expectancy needs to be


considered (if less than 10 years
to live then is screening
reasonable?). Current WHO
estimate for life expectancy at
birth is 74 years for males and 78
years for females; however,
based on the 2012 United Nations
Screening for colorectal cancer
30

Criteria Judgments Research evidence Additional considerations

World Population Prospects life


expectancy among Saudi
nationals is expected to increase
over the coming years.
Specifically, this report suggests
that currently 2.6% to 3.6% of
the population in KSA is aged 65
years or older, but by 2050 this
percent should increase to
approximately 18.4%.

The relative importance or values of the main outcomes of interest: USPSTF reports that persons
No undergoing colonoscopy experience
included Certainty of
Relative 2.8 higher (1.5 to 5.2) risk difference
studies Outcome the evidence
importance in complications than those not
(GRADE)
What is the
overall certainty
Very low undergoing colonoscopy. Serious
complications are defined as
of this evidence? Low perforations, hemorrhage,
Colorectal cancer-related mortality CRITICAL diverticulitis, cardiovascular
Moderate HIGH
events, severe abdominal pain,
High and death (USPSTF 2008).
Colorectal cancer-related incidence CRITICAL
Indirect evidence provided,

Benefits &
Important MODERATE examining studies of flexible
sigmoidoscopy pooled.
harms of uncertainty
the options or variability Serious complications of Flexible Initially, the KSA expert panel
Possibly Sigmoidoscopy (including perforations,
CRITICAL
said that the desirable anticipated
important hemorrhage, diverticulitis, cardiovascular LOW
Is there effects were probably large given
uncertainty events, severe abdominal pain, and death)
important doubts concerning application of
uncertainty or variability data to KSA; however, when
about how much
people value the Probably Summary of findings: CRC screening compared to no screening in
examining individual data for FS
main outcomes? no important and colonoscopy became more
asymptomatic, average risk population aged 70 years or older in Saudi Arabia
uncertainty clear the benefits of CRC
of variability Without screening.
With CRC Difference Relative
Outcome CRC
No screening
screening (95% CI) effect
Initially to address "Are the
important (RR)
desirable effects large relative to
uncertainty
Screening for colorectal cancer
31

Criteria Judgments Research evidence Additional considerations

of variability undesirable effects?" the KSA


(95% CI)
No known Expert Panel was split with a vote
of 5 for "Yes" and 4 for "Probably
undesirable
523 per 131 fewer per Yes". During the second review, a
RR 0.80
Colorectal cancer- 654 per 100000 100000 (from vote was not needed and overall
No related mortality 100000 (491 to 98 fewer to
(0.75 to
0.85) consensus given the evidence
Probably 556) 164 fewer) review was for "Yes."
no
Are the Additional indirectness because
desirable Uncertain Colorectal cancer- 1661 per
1462 per
100000
199 fewer per
100000 (from
RR 0.88 data does not specifically address
anticipated (0.80 to
effects large? Probably related incidence 100000 (1329 to 66 fewer to
0.96)
persons in this age group;
yes 1595) 332 fewer) however, complications from
screening technologies are
Yes expected to increase with the
Serious complications
Varies of Flexible
patient's age, such as perforation
rate.
Sigmoidoscopy
34 more per
No (including perforations,
hemorrhage,
0 per
0 per
100000
100000 (from not Given life expectancy, benefits
100000 estimable
Probably diverticulitis, (0 to 0)
0.06 more to
1.9 fewer)
are attenuated compared to
general population.
no cardiovascular events,
Are the severe abdominal pain,
undesirable Uncertain and death)
anticipated
effects small? Probably
yes
Yes
Varies
No
Are the
desirable effects
Probably
no
large relative to
undesirable Uncertain
effects?
Probably
yes
Screening for colorectal cancer
32

Criteria Judgments Research evidence Additional considerations

Yes
Varies
Minimal to no cost to patients
No living in KSA, both Saudi
Probably nationals and expatriates, as
either the government or
no
employer pays for necessary
Are the
resources
Uncertain health care.
required small? Probably
yes Lower expense experienced in the
private sector vs public sector.
Yes
Varies
Incremental cost-effectiveness ratio (ICER) for colonoscopy in Iran A cost-feasibility report was sent
estimated to be $8,700 per QALY13. CRC screening falls well below the forward to the ministry examining
50,000 ICER (generally acceptable willingness to pay threshold), and costs for different CRC screening
Resource technologies, age groups, and
below the GDP per Capita for Saudi Arabia ($25,851). Based on cost-
use lifetime. This data remains
No utility analyses, colonoscopies every 10 years are recommended15,16. unpublished; however, helped to
provide relative costs for
Probably consideration throughout the
no recommendation process.
Elderly patients, if diagnosed with
Is the
incremental cost
Uncertain
CRC, usually will not get
small relative to Probably radiation, chemo or surgery due
the net benefits? yes
to frailty.
Yes
Varies Discussion reflects that the
incremental cost is likely not
small relative to the net
benefits based on life expectancy
and quality of life; however,
uncertainty given lack of
Screening for colorectal cancer
33

Criteria Judgments Research evidence Additional considerations

data/evidence in this context.

Government-level recommendation would increase awareness of Variability existed in the KSA


screening recommendation. Panel concerning how a
recommendation for CRC
Physicians recommendation and understanding of the benefit of screening would impact health
screening are associated with intention to be screening22. inequalities. Topics considered
included: Possibly more health
inequalities if using FOBT because
Having heard of CRC screening, higher education, and knowledge of
literacy to read and follow
Increased screening benefits associated with increased intention to receive CRC
instructions is necessary; persons
screening among Turkish women23.
Probably living in rural areas may have
increased less access to medical care than
Almadi et al.11 identified that access to and barriers of CRC screening persons in urban settings.
What would be
the impact on
Uncertain differ between ethnic groups and communities; however, there is
Equity limited information as to the extent that a mass screening
health Probably recommendation would have on health inequalities.
Indirect evidence discussed was
inequities? reduced access to vaccinations when those
Reduced were implemented.
Varies
Potentially by recommending
against screening would increase
inequity for those healthy and
over 70.

In terms of expats, small number


still in country at 70 (ministry of
planning).
Screening for colorectal cancer
34

Criteria Judgments Research evidence Additional considerations

Decreased odds of receipt of colonoscopy independently associated with Low acceptability of screening
No lack of familiarity with CRC screening, distrust in Western medicine, and technologies by patients;
Probably embarrassment24 however, acceptability increases
no if recommended by a physician.
Is the option
Acceptability
acceptable to Uncertain Studies examining acceptability of repeat screening based on whether
sedated or not sedated for the procedure (i.e., colonoscopy) report no
key
stakeholders? Probably significant difference25.
yes
Yes A cross-sectional study was conducted in Riyadh to examine
acceptability of CRC screening. The majority of persons interviewed
Varies reported willingness to undergo CRC screening11.

Some barriers have been identified to acceptance and uptake of CRC Infrastructure limitations exist in
screening, based on a cross-sectional study conducted in Riyadh. KSA such as, a shortage of
Barriers include lack of knowledge about screening; inaccessibility of physicians to implement
physicians, settings, and organizations conducting the screening; access screening, trained clinical staff
No to the health care delivery system, lack of time for those intended to be (nurse endoscopists), or mail
Probably screened, transportation, financial barriers as well as fear from delivery in some rural areas
no receiving unwanted result as well as embarrassment or shame11. (specifically for FOBT). Wait times
are currently long to receive
Is the option Uncertain screening.
Feasibility feasible to
implement? Probably
yes Implementation is different than
acceptability.
Yes
Varies "Probably Yes" was the overall
consensus; however, concerns
noted about uncertainty around
feasibility and the need for
additional research.
Screening for colorectal cancer
35

Recommendation
Should CRC screening vs. no screening be used in asymptomatic, average risk population aged 70 years or older
in Saudi Arabia?
Undesirable consequences Undesirable consequences The balance between Desirable consequences Desirable consequences
Balance of clearly outweigh desirable probably outweigh desirable desirable and undesirable probably outweigh clearly outweigh undesirable
consequences consequences in most consequences in most consequences is closely undesirable consequences in consequences in most
settings settings balanced or uncertain most settings settings


Type of We recommend against offering this We suggest not offering this We suggest offering this
We recommend offering this option
recommendation option option option


The panel suggests not using colorectal cancer screening for asymptomatic persons at average risk aged 70 years or older (conditional
recommendation; low quality evidence)

Remarks:
Recommendation
- Consider that some individual patients might still benefit from screening (if healthy, lack of comorbidities and predicted survival beyond
10 years at the time of screening)
- Consider additional resources needed for mental health and social support if cancer is identified and surgery or other treatment may not
be offered or appropriate

Due to the expected reduced benefits experienced by patients aged 70 and older and increased risk in serious complications of some screening
Justification technologies, the undesirable consequences probably outweigh the desirable consequences in most settings. This is in contrast to screening in a
younger patient population where the desirable consequences are more clearly seen.
Subgroup
considerations
None

- Consider if this population is screened and untreatable cancer is found the effect the diagnosis will have on mental health
Implementation - Education and certifications needed for doctors, nurse endoscopists, and other clinical staff
considerations - Increase general awareness and knowledge of endoscopic procedures and technology
- Training of specialists on endoscopy (nurse endoscopists).

Monitoring and Database to capture screening results.


evaluation Implementation of technology to provide screening reminders to clinicians and patients (e.g., EMRs, mobile phone, etc.).
Screening for colorectal cancer
36

Quality indicators (KPIs) should be implemented among endoscopists and their peers to improve quality control.

Re-evaluate life expectancy and demographics


As population ages may need to re-evaluate recommendation
Research possibilities
Conduct monitoring and evaluation of patients/clinicians acceptability and uptake once recommendations implemented
Evaluation of access to care among different population groups (e.g., urban/rural, etc.)
Screening for colorectal cancer
37

Summary of Findings: Should CRC screening be used in average risk population aged 70 years or older compared to no screening?
CRC screening compared to no screening in asymptomatic, average risk population aged 70 years or older in Saudi Arabia

Bibliography (systematic reviews): Brenner H, Stock C, Hoffmeister M. Effect of screening sigmoidoscopy and screening colonoscopy on colorectal cancer incidence and mortality: systematic review and meta-analysis of
randomised controlled trials and observational studies. BMJ. 2014;348:g2467. Hewitson, P., Glasziou, P., Watson, E., Towler, B., & Irwig, L. (2008). Cochrane systematic review of colorectal cancer screening using the fecal
occult blood test (hemoccult): an update. The American journal of gastroenterology, 103(6), 1541-1549. Whitlock, E. P., Lin, J. S., Liles, E., Beil, T. L., & Fu, R. (2008). Screening for colorectal cancer: a targeted, updated
systematic review for the US Preventive Services Task Force. Annals of Internal Medicine, 149(9), 638-658.

Outcomes of participants Quality of the Relative Anticipated absolute effects


(studies) evidence effect
Follow-up (GRADE) (95% CI) Risk with no Risk difference with CRC
screening screening

Colorectal cancer-related mortality (CRC Mortality) 743587 RR 0.80 Study population


(8 RCTs) 1
HIGH (0.75 to 0.85)
654 per 100000 131 fewer per 100000
(164 fewer to 98 fewer)
Colorectal cancer-related incidence (CRC incidence) 743587 RR 0.88 Study population
(8 RCTs) 1
MODERATE 2 (0.80 to 0.96)
1661 per 100000 199 fewer per 100000
(332 fewer to 66 fewer)
Serious complications of Flexible Sigmoidoscopy (including perforations, hemorrhage, diverticulitis, 126985 not estimable Study population
cardiovascular events, severe abdominal pain, and death) (Serious complications (FS)) (6 observational LOW 34
studies) 0 per 100000 0 fewer per 100000
(0 fewer to 0 fewer)

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio; OR: Odds ratio;

GRADE Working Group grades of evidence


High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
1. We combined the results of RCTs examining the effect of flexible sigmoidoscopy (4 RCTs) and FOBT (4 RCTs) compared to no screening.
2. I squared = 82%, we lowered by one point because the analysis combined two different interventions with likely different treatment effect, heterogeneity was reduced when trials for each intervention analyzed separately
3. Test for heterogeneity, P= 0.26
4. Although the event rate is low, we did not downgrade for imprecision, because the sample size was large, it appears to an extremely rare event.
5. These estimates are obtained from a pooled estimate across 6 observational studies comparing flexible sigmoidoscopy to no screening.
Screening for colorectal cancer
38

Guideline Question 3: Should colonoscopy be used for CRC screening in asymptomatic average risk population compared to no
screening?

Problem: Screening for colorectal cancer Background and Objective: Colorectal cancer accounts for 10.4% of all newly diagnosed cases of cancer in Saudi
Option: Colonoscopy Arabia, second overall only to breast cancer. However, it is not clear if the available evidence support screening
Comparison: No Screening colonoscopy in average risk patients to help prevent cancer. We aim here to address the above question as a part of
Setting: Outpatient in KSA developing clinical practice guidelines on colorectal cancer in Saudi Arabia.
Perspective: Average risk population in Saudi
Arabia
Criteria Judgments Research evidence Additional considerations

2009 Cancer Registry reports baseline risk of 15/1000 in Saudi Arabia.


No
Probably no
Is there a Uncertain Generally low awareness about recommended CRC screening, especially among
persons with lower education21
Problem problem
priority?
Probably
yes

Yes
Varies

The relative importance or values of the main outcomes of interest: Serious complications are
No included defined as perforations,
studies
Certainty of the hemorrhage, diverticulitis,
Benefits &
What is the Very low Outcome
Relative
importance
evidence cardiovascular events,
overall certainty severe abdominal pain, and
harms of
the options
of this Low (GRADE)
death (USPSTF
evidence?
Moderate 2008). USPSTF reports that
persons undergoing
High Colorectal cancer-related mortality CRITICAL
LOW colonoscopy experience 2.8
higher (1.5 to 5.2) risk
Screening for colorectal cancer
39

difference in complications
Important Colorectal cancer-related incidence CRITICAL

than those not undergoing
uncertainty or VERY LOW
variability
colonoscopy. Serious
complications reported from
Possibly Serious Complication (including perforations, use of colonoscopy include
important hemorrhage, diverticulitis, cardiovascular CRITICAL
perforations, hemorrhage,
uncertainty or events, severe abdominal pain, and death) LOW
diverticulitis, cardiovascular
variability
Is there events, severe abdominal
important Probably no pain, and death (USPSTF
uncertainty important Summary of findings: Screening colonoscopy compared to no screening in 2008).
about how much uncertainty of asymptomatic, average risk population in Saudi Arabia
people value the variability
main outcomes? The panel recognizes that
No
Without With
Relative there might never be more
important Outcome screening screening
Difference effect direct or higher quality
uncertainty of (95% CI) (RR) evidence (e.g., randomized
colonoscopy colonoscopy
(95% CI)
variability controlled trials) because
No known colonoscopy is already
undesirable 2 fewer per accepted as gold standard.
1 per 1000 1000 (from 2
3 per 1000
(1 to 1) fewer to 2 Base overall low quality
No Colorectal cancer-
fewer)
RR 0.32 certainty in the evidence on
(0.23 to the harms data.
Probably no related mortality
0.43)
3 fewer per
Are the Uncertain 4 per 1000
1 per 1000 1000 (from 2 The desirable anticipated
(1 to 2) fewer to 3
desirable
anticipated
Probably fewer)
effects are large; however,
the panel recognized that the
effects large? yes
relative effect size could be
Yes 8 fewer per inflated due to the non-
randomized study design.
Varies 11 per 1000
3 per 1000
(1 to 8)
1000 (from 3
fewer to 10
fewer)
Colorectal cancer-
RR 0.31 The majority of
No related incidence
(0.12 to
0.77)
complications can be
10 fewer per related to the sedation
Are the Probably no 5 per 1000 1000 (from 3
undesirable 15 per 1000
(2 to 12) fewer to 13 process used during
anticipated Uncertain fewer) some colonoscopy
effects small?
Probably tests.
yes
Screening for colorectal cancer
40

Yes Serious Complication


(including
Varies perforations,
2.8 more per
hemorrhage,
0 per 1000 1000 (from not
diverticulitis, 0 per 1000
(0 to 0) 1.5 more to estimable
No cardiovascular
events, severe
5.2 more)

Probably no abdominal pain, and


death)
Are the
desirable effects
Uncertain
large relative to Probably
undesirable yes
effects?
Yes
Varies

Study conducted in Iran, estimates that the cost per cancer detected over 20
years (in Iranian Rials):
No
Probably no Government Sector
Colonoscopy = 0.28 billion
Are the
Uncertain Flexible sigmoidoscopy = 0.22 billion
FOBT = 0.42 billion
resources Probably CT colonography not available in public sector
required small? yes
Yes Private Sector
Resource Colonoscopy = 1.54 billion
use Varies Flexible sigmoidoscopy = 1.68 billion
FOBT = 1.60 billion
CT Colonography = 2.58 billion

CRC screening falls well below the 50,000 ICER (i.e., willingness to pay threshold). Multiple models have been
No Based on cost-utility analyses, FOBT annually or colonoscopy every 10 years are used to examine the cost
Is the
incremental cost Probably no recommended. effectiveness of colonoscopy
and found it to be
small relative to
the net
Uncertain comparable or cheaper to
benefits?
Probably other screening methods.
yes
Screening for colorectal cancer
41

Yes
Varies
Government-level recommendation would increase awareness of screening Groups of people that might
Increased recommendation. experience health inequities
Probably Physicians recommendation and understanding of the benefit of screening
from colorectal cancer
increased screening include person
are associated with intention to be screening22. living in rural parts of Saudi
What would be
the impact on
Uncertain Arabia versus urban areas;
Having heard of CRC screening, higher education, and knowledge of
Equity
health Probably screening benefits associated with increased intention to receive CRC
however, the panel did not
inequities? reduced feel confidence that
screening among Turkish women23
inequities would be
Reduced experienced.
Varies

Decreased odds of receipt of colonoscopy independently associated with


No lack of familiarity with CRC screening, distrust in Western medicine, and
Probably no embarrassment24

Is the option Uncertain Studies examining acceptability of repeat screening based on whether
Acceptability
acceptable to
key Probably sedated or not sedated for the procedure (i.e., colonoscopy) report no
stakeholders? yes significant difference25
Yes
A cross-sectional study conducted in Riyadh reported that persons who
Varies identified colonoscopy as a screening method had a higher willingness to
undergo CRC screening (odds ratio: 1.55; 95% CI:1.042.29)11

The Ministry will be required


No to coordinate the resources
Probably no for implementation.
Is the option
Feasibility feasible to Uncertain
Colonoscopy requires more
implement?
Probably skilled clinical staff, such as
yes nurse endoscopists, and
training programs to build
Yes
Screening for colorectal cancer
42

capacity.
Varies
There is some uncertainty
about the feasibility of
colonoscopy given the lack of
direct evidence and expected
resources needed to roll out
massive screening program
to all persons.

Colonoscopy, if results are


normal, does not have to
be repeated for 10 years,
reducing the burden
of population-level screening
and improving feasibility.
Screening for colorectal cancer
43

Recommendation
Should screening colonoscopy vs. no screening be used in asymptomatic, average risk population in Saudi
Arabia?
Undesirable consequences Undesirable consequences The balance between Desirable consequences Desirable consequences
Balance of clearly outweigh desirable probably outweigh desirable desirable and undesirable probably outweigh clearly outweigh undesirable
consequences consequences in most consequences in most consequences is closely undesirable consequences in consequences in most
settings settings balanced or uncertain most settings settings


Type of We recommend against offering this We suggest not offering this We suggest offering this
We recommend offering this option
recommendation option option option

The panel recommends screening colonoscopy rather than no screening for asymptomatic, average risk population (strong recommendation; low
quality evidence).
Recommendation
Remarks:
- Colonoscopy is considered the gold standard and there is high confidence in the magnitude of the association, even though that is based
on low quality evidence
- Some uncertainty is recognized given the indirect evidence regarding resources, values and preference, health inequalities, and feasibility

Desirable consequences clearly outweigh the undesirable consequences. Similar considerations to the above recommendations. The benefits of
screening, although lacking context-specific evidence, was felt to be significant enough with colonoscopy that they outweigh any potential
Justification
undesirable consequences (e.g., complications, costs, implementation barriers). This is especially true given colonoscopy represents the gold-
standard for CRC screening and should have the lowest amount of false positives and false negatives compared to other tools.
Subgroup
considerations
None

Implementation Education and certifications needed for doctors, nurse endoscopists, and other clinical staff
considerations Increase general awareness and knowledge of endoscopic procedures and technology

Monitoring and Implement quality control measures/indicators


evaluation Use of electronic charting for patients with automated algorithms to remind clinical staff when patients require repeated screening or
Screening for colorectal cancer
44

further testing

Conduct monitoring and evaluation of patients/clinicians acceptability and uptake once recommendations implemented
Prevalence studies of polyp detection using colonoscopy and serious complications experienced by patients
Research
possibilities
Assess the performance of colonoscopy in KSA
Evaluation of access to care among different population groups (e.g., urban/rural, etc.)
Age at which to initiate screening
Screening for colorectal cancer
45

Summary of Findings: Should colonoscopy be used for CRC screening in asymptomatic average risk population compared to no screening?

Screening colonoscopy compared to no screening in asymptomatic, average risk population in Saudi Arabia

Bibliography (systematic reviews): Brenner H, Stock C, Hoffmeister M. Effect of screening sigmoidoscopy and screening colonoscopy on colorectal cancer incidence and mortality: systematic review and meta-analysis of
randomised controlled trials and observational studies. BMJ. 2014;348:g2467.

Outcomes of participants Quality of the Relative effect Anticipated absolute effects


(studies) evidence (95% CI)
Follow-up (GRADE) Risk with no Risk difference with screening
screening colonoscopy

Colorectal cancer-related mortality (CRC mortality) 24116 RR 0.32 Study population


(3 observational LOW 1 (0.23 to 0.43) 2

studies) 2 9 3 per 1000 9 2 fewer per 1000


(2 fewer to 2 fewer)
Moderate
4 per 1000 3 3 fewer per 1000
(3 fewer to 2 fewer)
Colorectal cancer-related incidence (CRC incidence) 24116 RR 0.31 Study population
(5 observational VERY LOW 56 (0.12 to 0.77) 2

studies) 2 4 9 11 per 1000 9 8 fewer per 1000


(10 fewer to 3 fewer)
Moderate
15 per 1000 3 10 fewer per 1000
(13 fewer to 3 fewer)
Serious Complication (including perforations, hemorrhage, diverticulitis, cardiovascular events, 57742 not estimable Study population
severe abdominal pain, and death) (Serious complications) 8 (12 observational LOW
studies) 7 0 per 1000 0 fewer per 1000
(0 fewer to 0 fewer)

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio; OR: Odds ratio;

GRADE Working Group grades of evidence


High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
1. No explanation was provided
2. Estimate is taken from the meta-analysis of observational studies using adjusted values
3. This event rate is similar to what is observed in the control group of RCTs examining the effect of flexible sigmoidoscopy
Screening for colorectal cancer
46

4. Kahi CJ, Imperiale TF, Juliar BE, Rex DK. Effect of screening colonoscopy on colorectal cancer incidence and mortality. Clin Gastroenterol Hepatol. 2009;7(7):770-5; quiz 11. Manser CN, Bachmann LM, Brunner J, Hunold F,
Bauerfeind P, Marbet UA. Colonoscopy screening markedly reduces the occurrence of colon carcinomas and carcinoma-related death: a closed cohort study. Gastrointest Endosc. 2012;76(1):110-7. Doubeni CA, Weinmann S,
Adams K, Kamineni A, Buist DS, Ash AS, et al. Screening colonoscopy and risk for incident late-stage colorectal cancer diagnosis in average-risk adults: a nested case-control study. Ann Intern Med. 2013;158(5 Pt 1):312-20.
Brenner H, Chang-Claude J, Jansen L, Knebel P, Stock C, Hoffmeister M. Reduced risk of colorectal cancer up to 10 years after screening, surveillance, or diagnostic colonoscopy. Gastroenterology. 2014;146(3):709-17.
5. Risk of bias is high
6. I squared = 95%
7. Whitlock EP, Lin JS, Liles E, Beil TL, Fu R. Screening for colorectal cancer: a targeted, updated systematic review for the U.S. Preventive Services Task Force. Ann Intern Med. 2008;149(9):638-58.
8. I squared = 68%
9. includes perforation, bleeding, and death
10. Event rate are based only on two observational studies that provided crude numbers
Screening for colorectal cancer
47

Guideline Question 4: Should flexible sigmoidoscopy be used for CRC screening in asymptomatic average risk population compared to no
screening?
Problem: Screening for colorectal cancer Background and Objective: Colorectal cancer accounts for 10.4% of all newly diagnosed cases of cancer in Saudi
Option: Flexible sigmoidoscopy Arabia, second overall only to breast cancer. However, it is not clear if the available evidence support screening using
Comparison: No Screening flexible sigmoidoscopy in average risk patients to help prevent cancer. We aim here to address the above question as
Setting: Outpatient in KSA a part of developing clinical practice guidelines on colorectal cancer in Saudi Arabia.
Perspective: Average risk population in Saudi
Arabia

Criteria Judgments Research evidence Additional considerations

In Saudi Arabia, the 2010 cancer registry reported that 10.4% of persons were
diagnosed with colorectal cancer. This is the predominant cancer detected
among males and the third among females. 2009 Cancer Registry reports
No baseline risk of CRC in 15/1000 persons in Saudi Arabia8.
Probably no
Is there a Uncertain In 2005, of persons living in Saudi Arabia, approximately 38% did not identify
Problem problem at native Saudis20. The 2010 cancer registry also reported on the prevalence of
priority? Probably yes colorectal cancer among the non-Saudi population, living in Saudi Arabia. Of
Yes 3,265 cancer cases reported in 201, 11.6% were identified as colorectal,
second reported overall to breast cancer. Among males and females, CRC
Varies ranked first among men (14.1%) and second among women (8.7%).

Generally low awareness about recommended CRC screening, especially among


persons with lower education21.

The relative importance or values of the main outcomes of interest: Serious complications are
No included defined as perforations,
studies Certainty of the
Relative hemorrhage, diverticulitis,
What is the Outcome evidence
Benefits & overall Very low importance
(GRADE) cardiovascular events,
harms of certainty of severe abdominal pain,
the options this Low and death (USPSTF
evidence?
Moderate Mortality CRITICAL
2008). USPSTF reports
that persons undergoing
High
Screening for colorectal cancer
48

Criteria Judgments Research evidence Additional considerations

FS experience 0.34 higher


Important HIGH
(0.06 higher to 1.9 higher)
uncertainty or
variability
risk difference in
complications than those
Possibly Colorectal Cancer Incidence CRITICAL
LOW not undergoing FS.
important
Is there
uncertainty or
important The panel decided, based
variability Serious complications (including perforations,
uncertainty on the magnitude of the
about how
much people
Probably no hemorrhage, diverticulitis, cardiovascular
events, severe abdominal pain, and death)
CRITICAL
MODERATE low rate of serious
important complication from flexible
value the
uncertainty of sigmoidoscopy, to rate the
main
variability quality of the evidence
outcomes? Summary of findings: Flexible sigmoidoscopy compared to no screening for
No important asymptomatic, average risk population in Saudi Arabia
from low to moderate.
uncertainty of
variability Relative
Without
With flexible Difference effect
No known Outcome flexible
sigmoidoscopy
sigmoidoscopy (95% CI) (RR)
undesirable (95% CI)

No 1195 fewer
Probably no Mortality
4268 per
3073 per
1000000
per 1000000
(from 854
RR 0.72
(0.65 to
1000000
Are the
desirable
Uncertain (2774 to 3414) fewer to 1494 0.80)
fewer)
anticipated Probably yes
effects large?
Yes 12445 per
2732 fewer
Varies Colorectal Cancer 15176 per 1000000
per 1000000
(from 1669
RR 0.82
(0.75 to
Incidence 1000000 (11382 to
fewer to 3794 0.89)
13507)
fewer)
No
Are the
undesirable Probably no Serious
0 per 100000
0.34 more
not
anticipated complications 0 per 100000 per 100000
effects small? Uncertain (including
(0 to 0)
(from 0.06
estimable

Probably yes perforations, more to 1.9


Screening for colorectal cancer
49

Criteria Judgments Research evidence Additional considerations

Yes hemorrhage,
diverticulitis,
more)

Varies cardiovascular
events, severe
abdominal pain, and
No death)
Are the Probably no
desirable
effects large Uncertain
relative to
undesirable
Probably yes
effects?
Yes
Varies
No
Probably no
Are the
resources Uncertain
required
small? Probably yes
Yes
Varies
Resource Incremental cost-effectiveness ratio (ICER) for colonoscopy in Iran estimated No cost-effectiveness
use to be $8,700 per QALY13. CRC screening falls well below the 50,000 ICER analysis data to describe
No (generally acceptable willingness to pay threshold), and below the GDP per cost per QALY (i.e., ICER)
Is the
Probably no Capita for Saudi Arabia ($25,851). Based on cost-utility analyses, for using FS in Saudi
colonoscopies every 10 years are recommended15,16. Study conducted in Iran, Arabia or similar countries.
incremental
cost small
Uncertain estimates: Results from Iranian
relative to the Probably yes studies were determined to
be too indirect.
net benefits? Cost per cancer detected over 20 years in Iranian Rials:
Yes
Varies Government Sector
Screening for colorectal cancer
50

Criteria Judgments Research evidence Additional considerations

Colonoscopy = 0.28 billion (equivalent to 39,000 Riyals)


Flexible sigmoidoscopy = 0.22 billion (equivalent to 30,500 Riyals)

Private Sector

Colonoscopy = 1.54 billion


Flexible sigmoidoscopy = 1.68 billion

Government-level recommendation would increase awareness of screening


Increased recommendation.
Probably
increased Physicians recommendation and understanding of the benefit of screening are
What would
Equity
be the impact Uncertain associated with intention to be screening22
on health
inequities? Probably Having heard of CRC screening, higher education, and knowledge of screening
reduced benefits associated with increased intention to receive CRC screening among
Reduced Turkish women23
Varies
Decreased odds of receipt of colonoscopy independently associated with lack of
No familiarity with CRC screening, distrust in Western medicine, and
Probably no embarrassment24
Is the option
Acceptability
acceptable to Uncertain Flexible sigmoidoscopy was recognized as the least appreciated method for
key
stakeholders? Probably yes CRC screening based on a cross-sectional survey conducted in Riyadh11. FOBT
was associated with a decreased willingness to receive CRC screening (odds
Yes ratio 0.59; 95% CI: 0.38-0.91).
Varies
The Ministry will be
No required to coordinate the

Feasibility
Is the option
feasible to
Probably no resources for
implementation.
implement? Uncertain
Probably yes Flexible sigmoidoscopy
Screening for colorectal cancer
51

Criteria Judgments Research evidence Additional considerations

requires more skilled


Yes clinical staff, such as nurse
Varies endoscopists, and training
programs to build capacity.

There is some uncertainty


about the feasibility of FS
given the lack of direct
evidence and expected
resources needed to roll
out massive screening
program to all persons.

FS, if results are normal,


does not have to
be repeated for 3-to-5
years (if screening
annually with FIT),
reducing the burden
of population-level
screening and improving
feasibility.
Screening for colorectal cancer
52

Recommendation
Should flexible sigmoidoscopy vs. no screening be used for asymptomatic, average risk population in Saudi
Arabia?
Undesirable consequences Undesirable consequences The balance between Desirable consequences Desirable consequences
Balance of clearly outweigh desirable probably outweigh desirable desirable and undesirable probably outweigh clearly outweigh undesirable
consequences consequences in most consequences in most consequences is closely undesirable consequences in consequences in most
settings settings balanced or uncertain most settings settings


Type of We recommend against offering this We suggest not offering this We suggest offering this
We recommend offering this option
recommendation option option option


The panel recommends using flexible sigmoidoscopy (FS) for colorectal cancer screening rather than no screening for asymptomatic persons at
average risk (strong recommendation; moderate quality evidence)
Recommendation
Remarks:
This recommendation refers to FS screening every 5 years when combined with annual fecal occult blood (FOBT) or fecal
immunochemical (FIT) testing or every 3 years without annual FIT testing

Based on the evidence reviewed, the desirable consequences of offering FS versus no screening clearly outweighed the undesirable consequences
in most settings. The benefit of FS is less clear compared to that of colonoscopy as FS fails to rule out right-sided malignancy. That being said, the
Justification
benefits of screening using FS were still felt to clearly outweigh any undesirable consequences such as procedure complications, cost and
implementation barriers.
Subgroup
considerations
None

Implementation - Education and certifications needed for doctors, nurse endoscopists, and other clinical staff
considerations - Increase general awareness and knowledge of endoscopic procedures and technology

- Implement quality control measures/indicators


Monitoring and
evaluation
- Use of electronic charting for patients with automated algorithms to remind clinical staff when patients require repeated screening or
further testing

Research - Conduct monitoring and evaluation of patients/clinicians acceptability and uptake once recommendations implemented
Screening for colorectal cancer
53

possibilities - Prevalence studies of polyp detection using colonoscopy and serious complications experienced by patients
- Assess the performance of colonoscopy in KSA
- Evaluation of access to care among different population groups (e.g., urban/rural, etc.)
Screening for colorectal cancer
54

Summary of Findings: Should flexible sigmoidoscopy be used for CRC screening in asymptomatic average risk population compared to no
screening?

Flexible sigmoidoscopy compared to no screening for asymptomatic, average risk population in Saudi Arabia

Bibliography (systematic reviews): Brenner H, Stock C, Hoffmeister M. Effect of screening sigmoidoscopy and screening colonoscopy on colorectal cancer incidence and mortality: systematic review and meta-analysis of
randomised controlled trials and observational studies. BMJ. 2014;348:g2467. Whitlock, E. P., Lin, J. S., Liles, E., Beil, T. L., & Fu, R. (2008). Screening for colorectal cancer: a targeted, updated systematic review for the US
Preventive Services Task Force. Annals of Internal Medicine, 149(9), 638-658.

Outcomes of participants Quality of the evidence Relative effect Anticipated absolute effects
(studies) (GRADE) (95% CI)
Follow-up Risk with no Risk difference with flexible
screening sigmoidoscopy

Mortality 413945 RR 0.72 Study population


follow up: median 7 - 11.2 years (4 RCTs) HIGH 12 (0.65 to 0.80)
7 - 11.2 years 4268 per 1000000 1195 fewer per 1000000
(1494 fewer to 854 fewer)
Colorectal Cancer Incidence (CRC ) 413945 RR 0.82 Study population
follow up: median 7 - 11.2 years (4 RCTs) LOW 12 (0.75 to 0.89)
7 - 11.2 years 15176 per 1000000 2732 fewer per 1000000
(3794 fewer to 1669 fewer)
Serious complications (including perforations, hemorrhage, diverticulitis, cardiovascular events, 126985 not estimable Study population
severe abdominal pain, and death) (Serious complications) (6 observational MODERATE 34
studies) 0 per 100000 0 fewer per 100000
(0 fewer to 0 fewer)

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio; OR: Odds ratio;

GRADE Working Group grades of evidence


High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
1. selection bias
2. I squared 50%
3. Test for heterogeneity, P= 0.26
4. 95% CI: 0.06 to 1.9 per 1000 procedures; however, absolute effect is small
5. No explanation was provided
6. These estimates are obtained from a pooled estimate across 6 observational studies comparing flexible sigmoidoscopy to no screening.
Screening for colorectal cancer
55

Guideline Question 5: Should CT colonography be used for CRC screening in average risk population compared to colonoscopy?

Problem: Screening for colorectal cancer Background and Objective: Colorectal cancer accounts for 10.4% of all newly diagnosed cases of cancer in Saudi
Option: CT Colonography Arabia, second overall only to breast cancer. However, it is not clear if the available evidence support screening CT
Comparison: Colonoscopy colonography or colonoscopy in average risk patients to help prevent cancer. We aim here to address the above
Setting: Outpatient in KSA question as a part of developing clinical practice guidelines on colorectal cancer in Saudi Arabia.
Perspective: Average risk population in Saudi
Arabia

Additional
Domain Judgments Research evidence
considerations/explanations

Colorectal cancer is a major health problem


leading to more than 550,000 deaths
annually, with many developing among
Is the persons without identifiable risk factors1.
problem a
priority?
Five-year survival of people with colorectal
No Probably no Uncertain Probably yes Yes Varies cancer exceeds 90% if the disease is
diagnosed at an early stage, but only about
Is the 60% for patients with lymph node

problem involvement and under 10% if distant
Problem
severe?
No Probably no Uncertain Probably yes Yes Varies organ metastases are present26. In 2004,
the World Health Organization (WHO)
reported the death rate from CRC in Saudi

Arabia at 8.3%.
May skip for
individual
patient In Saudi Arabia, the 2010 cancer registry
perspective reported that 10.4% of persons were
diagnosed with colorectal cancer. This is the
predominant cancer detected among males
and the third among females. 2009 Cancer
Registry reports baseline risk of CRC in
Screening for colorectal cancer
56

Additional
Domain Judgments Research evidence
considerations/explanations

15/1000 persons in Saudi Arabia8.

In 2005, of persons living in Saudi Arabia,


approximately 38% did not identify at
native Saudis20. The 2010 cancer registry
also reported on the prevalence of
colorectal cancer among the non-Saudi
population, living in Saudi Arabia. Of 3,265
cancer cases reported in 2010, 11.6% were
identified as colorectal, second reported
overall to breast cancer. Among males and
females, CRC ranked first among men
(14.1%) and second among women
(8.7%).

Generally low awareness about


recommended CRC screening, especially
among persons with lower education21.

De Haan et al. (2012) and


Allameh et al. (2011)
conducted comprehensive
literature searches to identify
Test accuracy
sensitivity and specificity for
0.829
Pooled
(95% CI:
Pooled 0.95 CT colonography and
Very Very sensitivity CT sensitivity (95% CI: colonoscopy. Both studies
Inaccurate Uncertain Accurate Varies 0.74 to
inaccurate accurate colonography colonoscopy 0.74 to 1)
Diagnostic What is the 0.89) provide pooled estimates;
test test however, confidence in the
accuracy accuracy?
Pooled
0.914
Pooled 1 (95%
overall quality of the evidence
specificity CT
(95% CI:
specificity CI: 0.996 is low, mostly due to concerns
0.84 to
colonography
0.96)
colonoscopy to 1) with heterogeneity and
indirectness.

A recent commentary
(Alsanea, awaiting
publication), highlights the
Screening for colorectal cancer
57

Additional
Domain Judgments Research evidence
considerations/explanations

poor accuracy of CTC


detecting low tumors, as well
as the variability of the
current and previously
published literature.

Looking at sensitivity and


specificity, CTC does not
detect polyps less than 5 mm
and will miss more polyps
between 5 and 9 mm.

Is there
similarity Probably Probably not Not
Similar Uncertain Varies
similar similar similar
about how
Values and
much people
preferences
value the
main
outcomes?

Effect per 1000 patients/year for pre-


Test
test probability of 11.3%
Outcome Study design accuracy
QoE
CT colonography colonoscopy

True
94 (84 to 101) 107 (84 to 113)
positives
What is the Very low Low Moderate High
Certainty of certainty of TP absolute
13 fewer TP in CT colonography
the the evidence difference
evidence of test
observational
study
accuracy False
19 (29 to 12) 6 (29 to 0)
negatives

FN absolute
13 more FN in CT colonography
difference

True observational
811 (745 to 852) 887 (883 to 887)
negatives study
Screening for colorectal cancer
58

Additional
Domain Judgments Research evidence
considerations/explanations

TN absolute
76 fewer TN in CT colonography
difference

False
76 (142 to 35) 0 (4 to 0)
positives

FP absolute
76 more FP in CT colonography
difference

USPSTF reports that persons undergoing


colonoscopy experience 2.8 higher (1.5 to Low complications or burden
5.2) risk difference than those not from CTC. Lower radiation risk
undergoing colonoscopy. Serious than before; however,
complications reported from use of recognize the discomfort
What is the colonoscopy include perforations, experienced by the patients.
certainty if hemorrhage, diverticulitis, cardiovascular
Very low Low Moderate High
the evidence events, severe abdominal pain, and death2.
for any Sometimes more feasible
adverse because in Saudi Arabia there
effects or Based on a systematic review and meta-
is a long wait for endoscopy.
burden of the analysis of harms related to CT
test? colonography, the estimated CT
colonography-related colorectal perforation Repeat screening for CTC is 5
rate is 0.04%, 0.02% in asymptomatic years vs. 10 years for
subjects27. The CTC-induced surgery rate is colonoscopy.
0.008 % (1:12,500)27. Some concerns exist
around radiation used during the exam.

What is the
certainty of
the evidence
of effects of
Very low Low Moderate High
the
consequence
s of
management
(including
treatment
and natural
history) that
Screening for colorectal cancer
59

Additional
Domain Judgments Research evidence
considerations/explanations

is guided by
the test
results on
critical or
important
benefits?

How certain
Very low Low Moderate High
is the link
between test
results and
management
decisions?

What is the
overall
certainty of Very low Low Moderate High
the evidence
of effects
from the test

and
management
?

How
important are
these
outcomes?

Five-year survival of people


with colorectal cancer exceeds
How 90% if the disease is
Benefits substantial
and harms diagnosed at an early stage,
are the
but only about 60% for
desirable
anticipated patients with lymph node
effects? involvement and under 10% if
distant organ metastases are
present (Ries 2007).

How
Screening for colorectal cancer
60

Additional
Domain Judgments Research evidence
considerations/explanations

substantial
are the
undesirable
anticipated
effects?

Does the
balance
between Favours the comparison
desirable and Probably favours the comparison
undesirable Does not favour either the intervention or the
effects favour comparison
the Probably favours the intervention
diagnostic Favours the intervention
intervention
or the
comparison?

Cost of procedure as
diagnostic technology not
assuming that colonoscopy
will be needed after.

Estimated that cost for private


Are the hospitals for CTC is 2,000
resources Saudi Riyals and 3,000 for
No Probably no Uncertain Probably yes Yes Varies
required colonoscopy. Because the
small? (may
Resources same prep is used for both
skip for
individual tests and an additional prep
patient should be avoided, a
perspective) gastroenterologist is needed
to be on call when performing
CTC in case something is
detected.

Need more information on


local costs and resources.
Screening for colorectal cancer
61

Additional
Domain Judgments Research evidence
considerations/explanations

Incremental cost-effectiveness ratio (ICER)


for colonoscopy in Iran estimated to be
$8,700 per QALY13. CRC screening falls well
below the $50,000 per QALY (i.e.,
ICER/willingness to pay threshold). Based Indirect research from Gomes
on cost-utility analyses, colonoscopies et al., (2013) compared CTC
every 10 years are recommended15,16. with colonoscopy in Britain
Study conducted in Iran, estimates: and found CTC to be more
Is the cost effective: "3D-CTC
incremental No Probably no Uncertain Probably yes Yes Varies provided a similar number of LYs
Cost per cancer detected over 20 years (in
cost (or [life years] (7.737 vs 7.739) and
resource use) Riyals)
small relative
QALYs [quality-adjusted life
years] (7.013 vs 7.018) per
to the Government Sector individual compared with OC
benefits? [colonoscopy], and it was
Colonoscopy = 0.28 billion associated with substantially
CT colonography not available in lower mean costs per patient
(467 vs 583), leading to a
public sector
positive incremental net benefit."

Private Sector
Colonoscopy = 1.54 billion
CT colonography = 2.58 billion

Government-level recommendation would


increase awareness of screening
recommendation.

Probably Probably
What Increased
increased
Uncertain
reduced
Reduced Varies Physicians recommendation and
happens to understanding of the benefit of screening
Equity
health are associated with intention to be
inequities? screening22

Having heard of CRC screening, higher


education, and knowledge of screening
benefits associated with increased intention
Screening for colorectal cancer
62

Additional
Domain Judgments Research evidence
considerations/explanations

to receive CRC screening among Turkish


women23

Decreased odds of receipt of colonoscopy


independently associated with lack of
familiarity with CRC screening, distrust in
Is the option No Probably no Uncertain Probably yes Yes Varies Western medicine, and embarrassment24
acceptable to
Acceptability key
stakeholders
Studies examining acceptability of repeat
? screening based on whether sedated or not
sedated for the procedure (i.e.,
colonoscopy) report no significant
difference25

No Probably no Uncertain Probably yes Yes Varies


Is the option
Feasibility feasible to
implement?*

Screening for colorectal cancer
63

Recommendation
Should CT colonography vs. colonoscopy be used to diagnose colorectal cancer in average risk, asymptomatic
persons?
Undesirable The balance between Desirable
Undesirable The balance of desirable Desirable
consequences desirable and consequences
Overall balance of consequences clearly and undesirable consequences clearly
probably outweigh undesirable probably outweigh
consequences outweigh desirable consequences indicates outweigh undesirable
desirable consequences is too undesirable
consequences they are very similar* consequences
consequences uncertain* consequences


We recommend We suggest not to use
We suggest using the We recommend the
against the option or the option or to use No recommendation
option option
for the alternative the alternative


Panel decisions

The panel suggests using colonoscopy rather than CT colonography for diagnosis of asymptomatic, average risk patients (conditional
recommendation; low quality evidence)

Remarks:
Recommendation
(text)
The decision to use colonoscopy instead of CT colonography should be driven by feasibility and availability of the tests, as sometimes the
wait for endoscopy services is too long for asymptomatic patient screening
For patients preferring non-invasive screening, they may choose to undergo CT colonography initially with the understanding they would still
be subjected to the bowel preparation procedure and that CT colonography still has small risks of complications and the risk of radiation
exposure

Based on the evidence reviewed, the panel determined the desirable consequences and undesirable consequences of offering CT colonography
versus colonoscopy were similar in most settings. The benefit of CT colonography is less clear compared to that of colonoscopy, as CT colonography
Justification
requires similar bowel preparation and confirmatory screening using colonoscopy. That being said, given the availability of trained clinical staff and
endoscopic resources in the KSA, sometimes CT colonography wait times are shorter.

Implementation Consideration should be given to the availability of endoscopy services.


considerations Repeat screening mandates more frequent screening if using CT colonography (5 years) vs. colonoscopy (10 years).

Monitoring and Emphasis should be placed on the guidelines for conducting and reading the results from the CT colonography, including training and certification for
Screening for colorectal cancer
64

evaluation radiologists. Training and certifications should be tracked.


Radiation exposure should be noted and monitored for patients undergoing CT colonography.

Research priorities Additional research is needed on local preferences for screening technologies.
Screening for colorectal cancer
65

Evidence Profile: Should CT colonography be used for CRC screening in average risk population compared to colonoscopy?

Pooled sensitivity CT 0.829 (95% CI: 0.74 to 0.89) Pooled sensitivity 0.95 (95% CI: 0.74 to 1) Prevalence 11.3%
colonography colonoscopy

Pooled specificity CT 0.914 (95% CI: 0.84 to 0.96) Pooled specificity 1 (95% CI: 0.996 to 1)
colonography colonoscopy

Effect per 1000 patients/year


Factors that may decrease quality of evidence
of studies ( pre-test probability of 11.3% Test accuracy
Outcome Study design
of patients) QoE
Risk of Publication CT
Indirectness Inconsistency Imprecision colonoscopy
bias bias colonography
1
True positives 4 Studies observational not serious not serious not serious not serious 94 (84 to 101) 107 (84 to Low
(patients with colorectal cancer) 4018 Patients studies serious 113)

13 fewer TP in CT
colonography

False negatives 19 (29 to 12) 6 (29 to 0) Low


(patients incorrectly classified as not
having colorectal cancer) 13 more FN in CT
colonography
1
True negatives 4 Studies observational not serious serious not serious not serious 811 (745 to 887 (883 to Low
(patients without colorectal cancer) 4018 Patients studies serious 852) 887)

76 fewer TN in CT
colonography

False positives 76 (142 to 35) 0 (4 to 0) Low


(patients incorrectly classified as
having colorectal cancer) 76 more FP in CT
colonography

1. Not possible to calculate estimated sensitivity due to small numbers, results represent detection of adenomatous polyps 6 mm
Screening for colorectal cancer
66

Guideline Question 6: Should FS be used for CRC screening in average risk population compared to guaiac fecal occult blood testing
(gFOBT)?

Problem: Screening for colorectal cancer Background and Objective: Colorectal cancer accounts for 10.4% of all newly diagnosed cases of cancer in Saudi
Option: Flexible sigmoidoscopy Arabia, second overall only to breast cancer. However, it is not clear if the available evidence support screening FS
Comparison: gFOBT vs. gFOBT in average risk patients to help prevent cancer. We aim here to address the above question as a part of
Setting: Outpatient developing clinical practice guidelines on colorectal cancer in Saudi Arabia.
Perspective: Average risk population in Saudi
Arabia
Criteria Judgments Research evidence Additional considerations

In Saudi Arabia, the 2010 cancer registry reported that 10.4% of persons The panel identified that the
were diagnosed with colorectal cancer. This is the predominant cancer main concerns are regarding
No detected among males and the third among females. 2009 Cancer Registry the use of FS with FOBT
reports baseline risk of CRC in 15/1000 persons in Saudi Arabia8. (fecal immunochemical test -
Probably FIT not guaiac FOBT - gFOBT)
no
In 2005, of persons living in Saudi Arabia, approximately 38% did not versus FIT.
Problem
Is there a
problem
Uncertain identify at native Saudis20. The 2010 cancer registry also reported on the
priority? Probably prevalence of colorectal cancer among the non-Saudi population, living in Currently, gFOBT are in
yes Saudi Arabia. Of 3,265 cancer cases reported in 201, 11.6% were identified circulation but not used
as colorectal, second reported overall to breast cancer. Among males and widely.
Yes females, CRC ranked first among men (14.1%) and second among women
Varies (8.7%).

Generally low awareness about recommended CRC screening, especially


among persons with lower education21.

Summary of findings: Flexible sigmoidoscopy compared to FOBT for colorectal See Summary of Findings Tables
No cancer screening in asymptomatic, average risk persons in Saudi Arabia from Question 4. FS vs. No
What is the included screening and Question 6. FOBT
Benefits &
overall certainty studies See summary of findings tables below. vs. no screening.
harms of
of this
the options
evidence? Very low
Overall certainty in the
Low
Screening for colorectal cancer
67

evidence was lowered to very


Moderate low due to indirect
High comparison through no
screening.
Important
uncertainty USPSTF reports that persons
or variability undergoing flexible
sigmoidoscopy experience
Possibly 0.34 higher (0.06 to 1.9) risk
important
uncertainty difference than those not
Is there or variability undergoing flexible
important sigmoidoscopy. Serious
uncertainty Probably complications reported from
about how much no important use of flexible sigmoidoscopy
people value the uncertainty include perforations,
main outcomes? of variability hemorrhage, diverticulitis,
No cardiovascular events, severe
important abdominal pain, and death
uncertainty (USPSTF 2008).
of variability
No known FOBT is an un-invasive test
undesirable and no adverse events or
harms are expected. Holme
No et al. (2013) report no major
complications during the
Probably gFOBT test; however, 0.03%
no of participants suffered a
Are the
desirable Uncertain major complication after
follow-up.
anticipated
effects large? Probably
yes gFOBT based on guaiac-based
Yes tests which are outdated and
not useful. What about newer
Varies gFOBT tools?

Are the
undesirable
No
anticipated Probably
effects small? no
Screening for colorectal cancer
68

Uncertain
Probably
yes

Yes
Varies
No
Probably
Are the no
desirable effects
large relative to
Uncertain
undesirable Probably
effects? yes
Yes
Varies
Based on cost-utility analyses, FOBT performed annually are Costs associated with gFOBT
No recommended15,16. Study conducted in Iran, estimates: mailing to citizens, increased
frequency compared to FS.
Probably Government Sector
no FS has more upfront costs in
setting up but then less
Are the Uncertain Flexible sigmoidoscopy = 0.22 billion
frequency of repeated testing
resources FOBT = 0.42 billion
required small? Probably than gFOBT.
yes FS requires more
Resource Private Sector
use Yes infrastructure and man power
Flexible sigmoidoscopy = 1.68 billion
Varies than gFOBT.
FOBT = 1.60 billion Vote: 6 for uncertain re:
costs, 5 for probably not.

Is the CRC screening falls well below the 50,000 ICER (i.e., willingness to pay
incremental cost No threshold). ICER for FOBT in Iran estimated to be $9,067 when performed
small relative to
the net Probably annually13
benefits? no
Screening for colorectal cancer
69

Uncertain
Probably
yes
Yes
Varies
Government-level recommendations would increase awareness of screening Might be easier to get FS at
recommendations among health care professionals and patients. physician's office than gFOBT
Increased by mail.
Probably Physicians recommendation and understanding of the benefit of screening
increased are associated with intention to be screening22 gFOBT would have to be
through mechanism
What would be
the impact on
Uncertain Having heard of CRC screening, higher education, and knowledge of that didn't involve
Equity
health Probably screening benefits associated with increased intention to receive CRC reading/mailing. Concerns
inequities? reduced screening among Turkish women23 about the level of literacy
needed to perform self-
Reduced testing using gFOBT cause
Almadi et al.11 identified that access to and barriers of CRC screening differ
Varies between ethnic groups and communities; however, there is limited
uncertainty when evaluating
the impact on health
information as to the extent that a mass screening recommendation would
inequalities.
have on health inequalities.

Decreased odds of receipt of FOBT screening independently associated with


No
lack of familiarity with CRC screening, distrust in Western medicine, and
Probably embarrassment24
no
Flexible sigmoidoscopy was recognized as the least appreciated method for
Is the option
acceptable to
Uncertain CRC screening compared with FOBT based on a cross-sectional survey
Acceptability conducted in Riyadh11. FOBT was associated with a decreased willingness to
key Probably receive CRC screening (odds ratio 0.59; 95% CI: 0.38-0.91).
stakeholders? yes
Yes
Varies
Screening for colorectal cancer
70

gFOBT can be conducted as a home test, possibly leading to decreased


No feelings of embarrassment or vulnerability; however, Rainis et al., 2010,
Probably report that among Turkish women receiving counseling and home
no gFOBT tests, those without CRC-related symptoms were less likely to use
the test because of inconvenience related to the test and apprehension
Feasibility
Is the option
feasible to
Uncertain about dealing with something unclean.
implement? Probably
yes
Yes
Varies
Screening for colorectal cancer
71

Recommendation
Should flexible sigmoidoscopy vs. gFOBT be used for colorectal cancer screening in asymptomatic, average risk
persons in Saudi Arabia?
Undesirable consequences Undesirable consequences The balance between Desirable consequences Desirable consequences
Balance of clearly outweigh desirable probably outweigh desirable desirable and undesirable probably outweigh clearly outweigh undesirable
consequences consequences in most consequences in most consequences is closely undesirable consequences in consequences in most
settings settings balanced or uncertain most settings settings


Type of We recommend against offering this We suggest not offering this We suggest offering this
We recommend offering this option
recommendation option option option


The panel suggests using flexible sigmoidoscopy rather than guaiac fecal occult blood test (gFOBT) for colorectal cancer screening among
asymptomatic, average risk persons in the Kingdom of Saudi Arabia (conditional recommendation; very low quality evidence)
Recommendation
Remarks:
- gFOBT is an outdated, older technology
- FS is often done in combination with FOBT or FIT testing to ensure the entire colon is screened

The panel highlighted the current practices in KSA, which are that gFOBT is typically not performed for colorectal screening and less feasible to
implement because of access to postal services, and FS is typically not performed without a stool-based screening test; therefore the balance
Justification between desirable and undesirable consequences for these two methods is uncertain. That being said, given the benefit of screening using FS, as
well as the acceptability and feasibility, the panel would suggest this over gFOBT, with the caveat that the stool-based fecal immunochemistry
test (FIT) be used at annual intervals in combination with FS every five years.
Subgroup
considerations
None

FS is often done in combination with FOBT (FIT) testing to ensure the entire colon is screened
Implementation
considerations
Education and certifications needed for doctors, nurse endoscopists, and other clinical staff
Increase general awareness and knowledge of endoscopic procedures and technology

- Implement quality control measures/indicators


Monitoring and
evaluation
- Use of electronic charting for patients with automated algorithms to remind clinical staff when patients require repeated screening or
further testing
Screening for colorectal cancer
72

- Conduct monitoring and evaluation of patients/clinicians acceptability and uptake once recommendations implemented
Research
possibilities
- Assess the performance of FS with FOBT (FIT) in KSA
- Evaluation of access to care among different population groups (e.g., urban/rural, etc.)
Screening for colorectal cancer
73

Summary of Findings: Should FS be used for CRC screening in average risk population compared to guaiac fecal occult blood testing (gFOBT)?

gFOBT compared to No screening for Screening in Average risk population in Saudi Arabia
Bibliography (systematic reviews): Holme O, Bretthauer M, Fretheim A, Odgaard-Jensen J, Ho G. Flexible sigmoidoscopy versus faecal occult blood testing for colorectal cancer screening in asymptomatic individuals.
Cochrane Database Syst Rev 2013;9.

Outcomes of participants Quality of the evidence Relative effect Anticipated absolute effects
(studies) (GRADE) (95% CI)
Follow-up Risk with No screening Risk difference with FOBT

Mortality 329642 OR 0.84 Study population


(4 RCTs) MODERATE 1 (0.78 to 0.90)
10146 per 1000000 1610 fewer per 1000000
(2214 fewer to 1005 fewer)
Colorectal Cancer Incidence 329642 RR 0.93 Study population
(4 RCTs) LOW 23 (0.84 to 1.04)
18890 per 1000000 1322 fewer per 1000000
(3022 fewer to 756 more)
Serious complications not estimable Study population
(0 studies)
0 per 1000 0 fewer per 1000
(0 fewer to 0 fewer)

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio; OR: Odds ratio;

GRADE Working Group grades of evidence


High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
1. upper limit of CI cross 0.75
2. I squared 78%
3. Upper limit of CI is 1.04
Screening for colorectal cancer
74

Flexible sigmoidoscopy compared to no screening for asymptomatic, average risk population in Saudi Arabia
Bibliography (systematic reviews): Brenner H, Stock C, Hoffmeister M. Effect of screening sigmoidoscopy and screening colonoscopy on colorectal cancer incidence and mortality: systematic review and meta-analysis of
randomised controlled trials and observational studies. BMJ. 2014;348:g2467. Whitlock, E. P., Lin, J. S., Liles, E., Beil, T. L., & Fu, R. (2008). Screening for colorectal cancer: a targeted, updated systematic review for the US
Preventive Services Task Force. Annals of Internal Medicine, 149(9), 638-658.

Outcomes of participants Quality of the evidence Relative effect Anticipated absolute effects
(studies) (GRADE) (95% CI)
Follow-up Risk with no Risk difference with flexible
screening sigmoidoscopy

Mortality 413945 RR 0.72 Study population


follow up: median 7 - 11.2 years (4 RCTs) HIGH 12 (0.65 to 0.80)
7 - 11.2 years 4268 per 1000000 1195 fewer per 1000000
(1494 fewer to 854 fewer)
Colorectal Cancer Incidence (CRC ) 413945 RR 0.82 Study population
follow up: median 7 - 11.2 years (4 RCTs) LOW 12 (0.75 to 0.89)
7 - 11.2 years 15176 per 1000000 2732 fewer per 1000000
(3794 fewer to 1669 fewer)
Serious complications (including perforations, hemorrhage, diverticulitis, cardiovascular events, 126985 not estimable Study population
severe abdominal pain, and death) (Serious complications) (6 observational MODERATE 34
studies) 0 per 100000 0 fewer per 100000
(0 fewer to 0 fewer)

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio; OR: Odds ratio;

GRADE Working Group grades of evidence


High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
1. selection bias
2. I squared 50%
3. Test for heterogeneity, P= 0.26
4. 95% CI: 0.06 to 1.9 per 1000 procedures; however, absolute effect is small
5. No explanation was provided
6. These estimates are obtained from a pooled estimate across 6 observational studies comparing flexible sigmoidoscopy to no screening.
Screening for colorectal cancer
75

Guideline Question 7: Should FS be used for CRC screening in average risk population compared to colonoscopy?

Problem: Screening for colorectal cancer Background and Objective: Colorectal cancer accounts for 10.4% of all newly diagnosed cases of cancer in Saudi
Option: Flexible sigmoidoscopy Arabia, second overall only to breast cancer. However, it is not clear if the available evidence support screening FS
Comparison: Colonoscopy vs. colonoscopy in average risk patients to help prevent cancer. We aim here to address the above question as a part
Setting: Outpatient of developing clinical practice guidelines on colorectal cancer in Saudi Arabia.
Perspective: Average risk population in Saudi
Arabia

Criteria Judgments Research evidence Additional considerations

In Saudi Arabia, the 2010 cancer registry reported


that 10.4% of persons were diagnosed with
colorectal cancer. This is the predominant cancer
detected among males and the third among
females. 2009 Cancer Registry reports baseline risk
No of CRC in 15/1000 persons in Saudi Arabia8.

Probably no In 2005, of persons living in Saudi Arabia,


Uncertain approximately 38% did not identify at native
Is there a problem Saudis20. The 2010 cancer registry also reported on
Problem
priority? Probably yes the prevalence of colorectal cancer among the non-
Yes Saudi population, living in Saudi Arabia. Of 3,265
cancer cases reported in 201, 11.6% were identified
Varies as colorectal, second reported overall to breast
cancer. Among males and females, CRC ranked first
among men (14.1%) and second among women
(8.7%).

Generally low awareness about recommended CRC


screening, especially among persons with lower
education21.

Benefits & What is the overall Summary of findings: Flexible sigmoidoscopy compared Refer to Summary of Findings Tables from
harms of certainty of this No included to colonoscopy for colorectal cancer screening in
Screening for colorectal cancer
76

Criteria Judgments Research evidence Additional considerations

the options evidence? studies asymptomatic, average risk persons in Saudi Arabia Question 3. Colonoscopy vs. No screening and
Very low See summary of findings tables below.
Question 4. Flexible sigmoidoscopy vs. No
screening as this was deemed to be similar
Low indirect quality as an indirect comparison of the
two technologies.
Moderate
High USPSTF reports that persons undergoing
colonoscopy experience 2.8 higher (1.5 to 5.2)
risk difference of complications than those not
Important undergoing colonoscopy. Serious complications
uncertainty or reported from use of colonoscopy include
variability perforations, hemorrhage, diverticulitis,
cardiovascular events, severe abdominal pain,
Possibly and death (USPSTF 2008).
important
uncertainty or
variability USPSTF reports that persons undergoing flexible
Is there important sigmoidoscopy experience 0.34 higher (0.06 to
uncertainty about Probably no 1.9) risk difference than those not undergoing
how much people important flexible sigmoidoscopy. Serious complications
value the main uncertainty of reported from use of flexible sigmoidoscopy
outcomes? variability
include perforations, hemorrhage, diverticulitis,
No cardiovascular events, severe abdominal pain,
important and death (USPSTF 2008).
uncertainty of
variability
No known
undesirable

No
Are the desirable
Probably no
anticipated effects
large?
Uncertain
Probably yes
Yes
Screening for colorectal cancer
77

Criteria Judgments Research evidence Additional considerations

Varies

No
Probably no
Are the undesirable Uncertain
anticipated effects
small?
Probably yes
Yes
Varies

No
Probably no
Are the desirable
effects large
Uncertain
relative to Probably yes
undesirable effects?
Yes
Varies

Based on cost-utility analyses, colonoscopies every The resources needed for FS are less than the
No 10 years are recommended15,16. Study conducted in resources needed for colonoscopy.
Iran, estimates:
Probably no
Resource Are the resources
Uncertain Cost per cancer detected over 20 years (in Rials)
use required small? Probably yes Government Sector
Yes
Colonoscopy = 0.28 billion
Varies Flexible sigmoidoscopy = 0.22 billion
Screening for colorectal cancer
78

Criteria Judgments Research evidence Additional considerations

Private Sector
Colonoscopy = 1.54 billion
Flexible sigmoidoscopy = 1.68 billion

CRC screening falls well below the 50,000 ICER (i.e., Variability exists between public and private
No willingness to pay threshold). ICER for colonoscopy health care.
Probably no in Iran estimated to be $8,70013

Is the incremental Uncertain


cost small relative
to the net benefits? Probably yes
Yes
Varies

Physicians recommendation and understanding of Government-level recommendation would


the benefit of screening are associated with increase awareness of screening
Increased intention to be screening22 recommendation.
Probably
increased Having heard of CRC screening, higher education, Potentially could reduce health inequalities as
What would be the Uncertain and knowledge of screening benefits associated with
increased intention to receive CRC screening among
could train other health professionals to do FS,
especially generalists (would be more difficult
Equity impact on health
inequities? Probably Turkish women23 with colonoscopy).
reduced
Reduced Almadi et al.11 identified that access to and barriers Although currently in KSA only specialists are
of CRC screening differ between ethnic groups and doing FS or colonoscopies but if train family
Varies communities; however, there is limited information doctors or nurses to do FS.
as to the extent that a mass screening
recommendation would have on health inequalities.
Screening for colorectal cancer
79

Criteria Judgments Research evidence Additional considerations

Decreased odds of receipt of colonoscopy If sedation is a barrier to the procedure (requires


additional time away from work or a companion for
independently associated with lack of familiarity
care/travel support), FS could be more accessible.
with CRC screening, distrust in Western medicine,
and embarrassment24

No Studies examining acceptability of repeat screening


Probably no based on whether sedated or not sedated for the
procedure (i.e., colonoscopy) report no significant
Is the option Uncertain difference25
Acceptability acceptable to key
stakeholders? Probably yes
Yes A cross-sectional study in Riyadh reported that the
most commonly recognized tool for screening for
Varies CRC was colonoscopy (50.56%) and that persons
who recognized colonoscopy as a screening
technology were more willing to undergo CRC
screening11. Survey participants recognized flexible
sigmoidoscopy as the least appreciated screening
technology (14.7%), after colonoscopy, CT
colonography, and faecal occult blood testing11.

Most likely both would be feasible to implement.


No
Probably no
Is the option Uncertain
Feasibility feasible to
implement? Probably yes
Yes
Varies
Screening for colorectal cancer
80

Recommendation
Should flexible sigmoidoscopy vs. colonoscopy be used for colorectal cancer screening in asymptomatic,
average risk persons in Saudi Arabia?
Undesirable consequences Undesirable consequences The balance between Desirable consequences Desirable consequences
Balance of clearly outweigh desirable probably outweigh desirable desirable and undesirable probably outweigh clearly outweigh undesirable
consequences consequences in most consequences in most consequences is closely undesirable consequences in consequences in most
settings settings balanced or uncertain most settings settings


Type of We recommend against offering this We suggest not offering this We suggest offering this
We recommend offering this option
recommendation option option option


The panel suggests using colonoscopy rather than flexible sigmoidoscopy for colorectal cancer screening among asymptomatic, average risk
persons (conditional recommendation; low quality evidence)
Remarks:
Recommendation
- FS needs to be done at least twice as often (every 3-to-5 years depending on whether FIT provided annually)
- Consider that FS misses right-sided disease
- Benefit of FS may be more if combined with FOBT or FIT

The panel determined that while many factors are similar between the two methods, patients would value the reduced screening frequency and
confirmatory results of colonoscopy more versus FS, given the close balance between the benefits and harms, and resource requirements. The
Justification
panel recognized that due to the indirect evidence and other factors introducing uncertainty, that some patients would prefer colonoscopy;
however, some would not.
Subgroup
considerations
None

- FS is often done in combination with FOBT (FIT) testing to ensure the entire colon is screened
Implementation
considerations
- Education and certifications needed for doctors, nurse endoscopists, and other clinical staff
- Increase general awareness and knowledge of endoscopic procedures and technology

- Implement quality control measures/indicators


Monitoring and
evaluation
- Use of electronic charting for patients with automated algorithms to remind clinical staff when patients require repeated screening or
further testing
Screening for colorectal cancer
81

Other questions to address in future CPG:


Combination FIT/FS versus colonoscopy
Use of FIT versus no screening
Research
possibilities
Use of FIT versus C-scope for screening
DNA testing versus no screening
DNA testing versus colonoscopy
DNA testing versus FIT
Screening for colorectal cancer
82

Summary of Findings: Should FS be used for CRC screening in average risk population compared to colonoscopy?

Screening colonoscopy compared to no screening in asymptomatic, average risk population in Saudi Arabia
Bibliography (systematic reviews): Brenner H, Stock C, Hoffmeister M. Effect of screening sigmoidoscopy and screening colonoscopy on colorectal cancer incidence and mortality: systematic review and meta-analysis of
randomised controlled trials and observational studies. BMJ. 2014;348:g2467.

Outcomes of participants Quality of the Relative effect Anticipated absolute effects


(studies) evidence (95% CI)
Follow-up (GRADE) Risk with no Risk difference with screening
screening colonoscopy

Colorectal cancer-related mortality (CRC mortality) 24116 RR 0.32 Study population


(3 observational LOW 1 (0.23 to 0.43) 2

studies) 2 9 3 per 1000 9 2 fewer per 1000


(2 fewer to 2 fewer)
Moderate
4 per 1000 3 3 fewer per 1000
(3 fewer to 2 fewer)
Colorectal cancer-related incidence (CRC incidence) 24116 RR 0.31 Study population
(5 observational VERY LOW 56 (0.12 to 0.77) 2

studies) 2 4 9 11 per 1000 9 8 fewer per 1000


(10 fewer to 3 fewer)
Moderate
15 per 1000 3 10 fewer per 1000
(13 fewer to 3 fewer)
Serious Complication (including perforations, hemorrhage, diverticulitis, cardiovascular events, 57742 not estimable Study population
severe abdominal pain, and death) (Serious complications) 8 (12 observational LOW
studies) 7 0 per 1000 0 fewer per 1000
(0 fewer to 0 fewer)

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio; OR: Odds ratio;

GRADE Working Group grades of evidence


High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
1. No explanation was provided
2. Estimate is taken from the meta-analysis of observational studies using adjusted values
Screening for colorectal cancer
83

3. This event rate is similar to what is observed in the control group of RCTs examining the effect of flexible sigmoidoscopy
4. Kahi CJ, Imperiale TF, Juliar BE, Rex DK. Effect of screening colonoscopy on colorectal cancer incidence and mortality. Clin Gastroenterol Hepatol. 2009;7(7):770-5; quiz 11. Manser CN, Bachmann LM, Brunner J, Hunold F,
Bauerfeind P, Marbet UA. Colonoscopy screening markedly reduces the occurrence of colon carcinomas and carcinoma-related death: a closed cohort study. Gastrointest Endosc. 2012;76(1):110-7. Doubeni CA, Weinmann S,
Adams K, Kamineni A, Buist DS, Ash AS, et al. Screening colonoscopy and risk for incident late-stage colorectal cancer diagnosis in average-risk adults: a nested case-control study. Ann Intern Med. 2013;158(5 Pt 1):312-20.
Brenner H, Chang-Claude J, Jansen L, Knebel P, Stock C, Hoffmeister M. Reduced risk of colorectal cancer up to 10 years after screening, surveillance, or diagnostic colonoscopy. Gastroenterology. 2014;146(3):709-17.
5. Risk of bias is high
6. I squared = 95%
7. Whitlock EP, Lin JS, Liles E, Beil TL, Fu R. Screening for colorectal cancer: a targeted, updated systematic review for the U.S. Preventive Services Task Force. Ann Intern Med. 2008;149(9):638-58.
8. I squared = 68%
9. includes perforation, bleeding, and death
10. Event rate are based only on two observational studies that provided crude numbers
Screening for colorectal cancer
84

Flexible sigmoidoscopy compared to no screening for asymptomatic, average risk population in Saudi Arabia
Bibliography (systematic reviews): Brenner H, Stock C, Hoffmeister M. Effect of screening sigmoidoscopy and screening colonoscopy on colorectal cancer incidence and mortality: systematic review and meta-analysis of
randomised controlled trials and observational studies. BMJ. 2014;348:g2467. Whitlock, E. P., Lin, J. S., Liles, E., Beil, T. L., & Fu, R. (2008). Screening for colorectal cancer: a targeted, updated systematic review for the US
Preventive Services Task Force. Annals of Internal Medicine, 149(9), 638-658.

Outcomes of participants Quality of the evidence Relative effect Anticipated absolute effects
(studies) (GRADE) (95% CI)
Follow-up Risk with no Risk difference with flexible
screening sigmoidoscopy

Mortality 413945 RR 0.72 Study population


follow up: median 7 - 11.2 years (4 RCTs) HIGH 12 (0.65 to 0.80)
7 - 11.2 years 4268 per 1000000 1195 fewer per 1000000
(1494 fewer to 854 fewer)
Colorectal Cancer Incidence (CRC ) 413945 RR 0.82 Study population
follow up: median 7 - 11.2 years (4 RCTs) LOW 12 (0.75 to 0.89)
7 - 11.2 years 15176 per 1000000 2732 fewer per 1000000
(3794 fewer to 1669 fewer)
Serious complications (including perforations, hemorrhage, diverticulitis, cardiovascular events, 126985 not estimable Study population
severe abdominal pain, and death) (Serious complications) (6 observational MODERATE 34
studies) 0 per 100000 0 fewer per 100000
(0 fewer to 0 fewer)

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio; OR: Odds ratio;

GRADE Working Group grades of evidence


High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
1. selection bias
2. I squared 50%
3. Test for heterogeneity, P= 0.26
4. 95% CI: 0.06 to 1.9 per 1000 procedures; however, absolute effect is small
5. No explanation was provided
6. These estimates are obtained from a pooled estimate across 6 observational studies comparing flexible sigmoidoscopy to no screening.
Screening for colorectal cancer
85

Appendix 2: Search Strategies and Results

Benefits & Harms Searches:

Data base: EMBASE/PubMed/Cochrane


Search strategy: Date of search: Dec. 23, 2104
1
exp colon tumor/ or exp colon cancer/ or exp colon carcinoma/ or exp colon adenoma/ or exp colon adenocarcinoma/ or exp rectum tumor/ or
exp rectum cancer/ or exp rectum carcinoma/ or exp rectum adenoma/
243006
2
(colorectal or CRC or "large bowl" or colon).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device
manufacturer, drug manufacturer, device trade name, keyword]
381754
3
(colonoscopy or endoscopy or sigmoidoscopy or polypectomy or colonography or SIG or FSIG or CTC or gFOBT or FOBT or FOB or FIT or faecal or
fecal or feces or faeces).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug
manufacturer, device trade name, keyword]
419746
4
((colorectal* or CRC or colon or colonic or bowel* or intestine or large intestine or rectal or rectum or sigmoid or anal or anus) and (cancer or
neoplasm* or malign* or tumor* or tumour or carcinom* or sarcom* or adenocarcinom* or adeno-carcinom* or adenom* or lesion*)).mtitl.
524
5
randomized controlled trial/ or randomization/ or controlled study/ or multicenter study/ or trial/ or placebo/
4726119
6
relative risk/ or relative risks/
632313
7
rate/ or rates/ or ratio/ or ratios/

(Colonography (includes: CT colonography, CT colonography screening, virtual colonography) OR colography OR


CTC OR computerized tomographic colonoscopy OR virtual colonoscopy OR virtual endoscopy OR ct colonoscopy
OR ct pneumocolon)
AND
(Colonoscopy (includes:optical colonoscopy) OR coloscopy OR OC)

Records Retrieved 146

Summary of Searches: Benefits & Harms

Total No. Retrieved: 146


PubMed: 87
Embase: 59
Cochrane Library: 5
Duplicates: 5
No. Total 141
without duplicates:
Screening (Title and Abstract Review)
No. Excluded: 136
Included for Full Text 7
review:
Selection (Full Text Review)
No. Excluded: 1
Reasons for exclusions:
1. Symptomatic patients
2. Abstract only
Screening for colorectal cancer
86

Patients Values and Preferences Searches:

Data base: PubMed, EMBASE


Search strategy: Date of search: Nov. 29, 2014
1. Saudi Arab$.mp,in. or Saudi Arabia/
2. Riyadh.mp,in.
3. Jeddah.mp,in.
4. Kh*bar.mp,in.
5. Dammam.mp,in.
6. 1 or 2 or 3 or 4 or 5
7. Kuwait$.mp,in. or Kuwait/
8. United Arab Emirates.mp,in. or United Arab Emirates/
9. Qatar$.mp,in. or Qatar/
10. Oman$.mp,in. or Oman/
11. Yemen$.mp,in. or Yemen/
12. Bahr*in$.mp,in. or Bahrain/
13. 7 or 8 or 9 or 10 or 11 or 12
14. Middle East$.mp,in. or Middle East/
15. Jordan$.mp,in. or Jordan/
16. Libya$.mp,in. or Libya/
17. Egypt$.mp,in. or Egypt/
18. Syria$.mp,in. or Syria/
19. Iraq$/ or Iraq.mp,in.
20. Morocc$.mp,in. or Morocco/
21. Tunisia$.mp,in. or Tunisia/
22. Leban$.mp,in. or Lebanon/
23. West Bank.mp,in.
24. Iran$.mp,in. or Iran/
25. Turkey/ or (Turkey or Turkish).mp,in.
26. Algeria$.mp,in. or Algeria/
27. Arab$.mp,in. or Arabs/
28. 14 or 15 or 16 or 17 or 18 or 19 or 20 or 21 or 22 or 23 or 24 or 25 or 26
29. 27 or 28
30. 6 or 13 or 29
31. patient$ participation.mp. or exp patient participation/
32. patient$ satisfaction.mp. or exp patient satisfaction/
33. attitude to health.mp. or exp Attitude to health/
34. (patient$ preference$ or patient$ perception$ or patient$ decision$ or patient$ perspective$ or user$ view$ or
patient$ view$ or patient$ value$).mp.
35. (patient$ utilit$ or health utilit$).mp.
36. health related quality of life.mp. or exp "quality of life"/
37. (health stat$ utilit$ or health stat$ indicator$ or (health stat$ adj 2 valu$)).mp. or exp Health Status Indicators/
38. 31 or 32 or 33 or 34 or 35 or 36 or 37
39. client$ participation.mp. or exp client participation/
40. client$ satisfaction.mp. or exp client satisfaction/
41. exp Health Attitudes/
42. (patient$ preference$ or patient$ perception$ or patient$ decision$ or patient$ perspective$ or user$ view$ or
patient$ view$ or patient$ value$ or patient$ attitude$).mp.
43. (patient$ utilit$ or health utilit$).mp.
44. health related quality of life.mp. or exp "quality of life"/
45. (health stat$ utilit$ or health stat$ indicator$ or (health stat$ adj 2 valu$)).mp.
46. (standard gambl$ or time trade off or willingness to pay or visual analog scale or (VAS or "visual analog$ adj 2
scal$")).mp.
47. (colorectal or CRC or "large bowl" or colon).mp. [mp=ti, ab, sh, hw, tn, ot, dm, mf, dv, kw, nm, kf, px, rx, an, ui,
tc, id, tm]
48. (colonoscopy or endoscopy or sigmoidoscopy or polypectomy or colonography or SIG or FSIG or CTC or gFOBT or
Screening for colorectal cancer
87

FOBT or FOB or FIT or faecal or fecal or feces or faeces).mp. [mp=ti, ab, sh, hw, tn, ot, dm, mf, dv, kw, nm, kf, px, rx,
an, ui, tc, id, tm]
49. 47 or 48
50. 39 or 40 or 41 or 42 or 43 or 44 or 45 or 46
51. 30 and 38 and 49 and 50

Records Retrieved 676

Summary of Searches: Patients Values and Preferences


Total No. Retrieved: 676
Medline & 676
EMBASE &
PsychINFO
Duplicates: 106 106
No. Total 570
without duplicates:
Screening (Title and Abstract Review)
No. Excluded: 524
Included for Full Text 46
review:
Selection (Full Text Review)
No. Excluded: 40
Reasons for exclusions:
1. Does not address values or preferences of screening
2. Not available
3. Patients previously diagnosed with CRC
4. Does not address cost-effectiveness

Cost-Effectiveness Search:

Data base: PubMed, EMBASE


Search strategy: Date of search: Nov. 29, 2014
1. (colorectal or CRC or "large bowl" or colon).mp. [mp=ti, ab, sh, hw, tn, ot, dm, mf, dv, kw, nm, kf, px, rx, an, ui, tc,
id, tm]
2. (colonoscopy or endoscopy or sigmoidoscopy or polypectomy or colonography or SIG or FSIG or CTC or gFOBT or
FOBT or FOB or FIT or faecal or fecal or feces or faeces).mp. [mp=ti, ab, sh, hw, tn, ot, dm, mf, dv, kw, nm, kf, px, rx,
an, ui, tc, id, tm]
3. 1 or 2
4. Economics/
5. "costs and cost analysis"/
6. Cost allocation/
7. Cost-benefit analysis/
8. Cost control/
9. Cost savings/
10. Cost of illness/
11. Cost sharing/
12. "deductibles and coinsurance"/
13. Medical savings accounts/
14. Health care costs/
15. Direct service costs/
16. Drug costs/
17. Employer health costs/
Screening for colorectal cancer
88

18. Hospital costs/


19. Health expenditures/
20. Capital expenditures/
21. Value of life/
22. exp economics, hospital/
23. exp economics, medical/
24. Economics, nursing/
25. Economics, pharmaceutical/
26. exp "fees and charges"/
27. exp budgets/
28. (low adj cost).mp.
29. (high adj cost).mp.
30. (health?care adj cost$).mp.
31. (fiscal or funding or financial or finance).tw.
32. (cost adj estimate$).mp.
33. (cost adj variable).mp.
34. (unit adj cost$).mp.
35. (economic$ or pharmacoeconomic$ or price$ or pricing).tw.
36. 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 or 16 or 17 or 18 or 19 or 20 or 21 or 22 or 23 or 24
or 25 or 26 or 27 or 28 or 29 or 30 or 31 or 32 or 33 or 34 or 35
37. "costs and cost analysis"/
38. Cost allocation/
39. Cost-benefit analysis/
40. Cost savings/
41. Health care costs/
42. Direct service costs/
43. Drug costs/
44. Health expenditures/
45. Capital expenditures/
46. Value of life/
47. (health?care adj cost$).mp.
48. (cost adj estimate$).mp.
49. (cost adj variable).mp.
50. (economic$ or pharmacoeconomic$ or price$ or pricing).tw.
51. 37 or 38 or 39 or 40 or 41 or 42 or 43 or 44 or 45 or 46 or 47 or 48 or 49 or 50
52. Saudi Arab$.mp,in. or Saudi Arabia/
53. Riyadh.mp,in.
54. Jeddah.mp,in.
55. Kh*bar.mp,in.
56. Dammam.mp,in.
57. 52 or 53 or 54 or 55 or 56
58. Kuwait$.mp,in. or Kuwait/
59. United Arab Emirates.mp,in. or United Arab Emirates/
60. Qatar$.mp,in. or Qatar/
61. Oman$.mp,in. or Oman/
62. Yemen$.mp,in. or Yemen/
63. Bahr*in$.mp,in. or Bahrain/
64. 58 or 59 or 60 or 61 or 62 or 63
65. Middle East$.mp,in. or Middle East/
66. Jordan$.mp,in. or Jordan/
67. Libya$.mp,in. or Libya/
68. Egypt$.mp,in. or Egypt/
69. Syria$.mp,in. or Syria/
70. Iraq$/ or Iraq.mp,in.
71. Morocc$.mp,in. or Morocco/
72. Tunisia$.mp,in. or Tunisia/
Screening for colorectal cancer
89

73. Leban$.mp,in. or Lebanon/


74. West Bank.mp,in.
75. Iran$.mp,in. or Iran/
76. Turkey/ or (Turkey or Turkish).mp,in.
77. Algeria$.mp,in. or Algeria/
78. Arab$.mp,in. or Arabs/
79. 65 or 66 or 67 or 68 or 69 or 70 or 71 or 72 or 73 or 74 or 75 or 76 or 77
80. 78 or 79
81. 57 or 64 or 80
82. economics/ or exp economics, hospital/ or exp economics, medical/ or economics, nursing/ or economics,
pharmaceutical/
83. exp "Costs and Cost Analysis"/
84. Value-Based Purchasing/
85. exp "Fees and Charges"/
86. budget$.mp. or Budgets/
87. (low adj cost).mp.
88. (high adj cost).mp.
89. (health?care adj cost$).mp.
90. (cost adj estimate$).mp.
91. (cost adj variable$).mp.
92. (unit adj cost$).mp.
93. (fiscal or funding or financial or finance).tw.
94. (economic$ or pharmacoeconomic$ or price$ or pricing).tw.
95. 82 or 83 or 84 or 85 or 86 or 87 or 88 or 89 or 90 or 91 or 92 or 93 or 94
96. economic evaluation$.mp. or exp economic evaluation/
97. fee$.mp. or exp fee/
98. health care cost$.mp. or exp "health care cost"/
99. hospital cost$.mp. or exp "hospital cost"/
100. pharmacoeconomics.mp. or exp pharmacoeconomics/
101. health economics.mp. or health economics/
102. budget$.mp. or budget/
103. socioeconomics.mp. or socioeconomics/
104. 96 or 97 or 98 or 99 or 100 or 101
105. 102 or 104
106. 103 or 105
107. (low adj cost).mp.
108. (high adj cost).mp.
109. (health?care adj cost$).mp.
110. (cost adj estimate$).mp.
111. (cost adj variable$).mp.
112. (unit adj cost$).mp.
113. (fiscal or funding or financial or finance).tw.
114. (economic$ or pharmacoeconomic$ or price$ or pricing).tw.
115. 107 or 108 or 109 or 110 or 111 or 112 or 113 or 114
116. 106 or 115
117. Socioeconomics/
118. Cost benefit analysis/
119. Cost effectiveness analysis/
120. Cost of illness/
121. Cost control/
122. Economic aspect/
123. Financial management/
124. Health care cost/
125. Health care financing/
126. Health economics/
127. Hospital cost/
Screening for colorectal cancer
90

128. (fiscal or financial or finance or funding).tw.


129. Cost minimization analysis/
130. (cost adj estimate$).mp.
131. (cost adj variable$).mp.
132. (unit adj cost$).mp.
133. 117 or 118 or 119 or 120 or 121 or 122 or 123 or 124 or 125 or 126 or 127 or 128 or 129 or 130 or 131 or 132
134. 3 and 36 and 51 and 81 and 95 and 116 and 133

Records Retrieved 426

Summary of Searches: Cost-Effectiveness

Total No. Retrieved: 426


Medline:
Embase:
Duplicates: 217 217
No. Total 202
without duplicates:
Screening (Title and Abstract Review)
No. Excluded: 195
Included for Full Text 7
review:
Selection (Full Text Review)
No. Excluded: 5
Reasons for exclusions:
1. No screening costs included
2. Full article not available