Metodologia cercetrii tiinifice

Colectarea datelor Strategii de msurare

Corin Badiu, 2008

Obiective
Stabilirea tipurilor de variabile

Surse IT de date Identifica si localizeaz seturile corecte de date

In instituie In afara instituiei

Strategii de msurare
Analiza, interpretarea si raportarea rezultatelor

Selecteaz programul adecvat: Excel, SPSS Folosete programele pentru analize statistice simple si prezentarea grafica a rezultatelor Interpreteaz rezultatele

Tipuri de variabile
Variabile de confuzie*

Predictor*

Rezultat

Modificatori ai efectului*
*Considerate general ca expunere la factori de risc

Tipuri de studii clinice

Studii fr variabile

Studii de caz, serii de cazuri, editoriale, opinii / comentarii, rapoarte review Studii descriptive

Studii cu o singura variabila

Studii cu 2 variabile

Experimente Studii observaionale Meta-analize si review-uri sistematice

Ierarhia tipurilor de studii clinice

Studii clinice

Descriptive Experimentale Cohorta

Analitice Observationale Caz-control Cross-sectional

Variabile

Variabila predictor (independenta)

Variabila rezultat (dependenta)

Evidence Based Medicine

Metode de tratament susinute de dovezi clinice si de cercetare. Necesita integrarea celor mai bune dovezi din cercetare pentru diagnostic si tratament cu experiena clinica. Ia in considerare ce este optim pentru fiecare pacient precum i preferinele acestuia.

Realitatea
Cercetarea asupra eficientei de tratament face subiectul unui numr mic de articole. Evidence based medicine este considerat un concept ce folosete baze de date inclusiv studii sistematice de caz pentru a ghida intervenii terapeutice. Dovezile trebuie evaluate intr-un context terapeutic efectiv, Ce tip de intervenie capt sens pentru mine ca practician?

ntrebri clinice
Care este cea mai bun alegere terapeutic pentru pacientul meu? Este acest program suficient de bine documentat teoretic? Funcioneaz acest program terapeutic? Ct timp dureaz acest program? Ce urmeaz dup aceea?

Utilitatea clinicii!

Clinicienii Sunt n linia I a asistentei medicale Au expertiza clinica necesara i cunosc bine pacienii Sunt formai pentru gndire tiinifica Sunt obinuii cu colectarea datelor tiu sa identifice rezultate

Msurtori de baz
O Linie de baz este o msurtoare a ratei de rspuns in absena tratamentului Linii de baz Stabilete necesitatea tratamentului Permite mbuntirea documentaiei Ne permite s mbuntim studiul

Date de baz
Se creeaz un set de exemplare ale intelor studiului Pregtim o fi de nregistrare Folosim msurtori conform criteriilor de referin

Strategii de Colectare a Datelor

ntotdeauna alegei mai mult dect o msurtoare Verific acurateea datelor de baz Selecteaz designul cercetrii clinice

Design de Cercetare Clinic

ABA design Test, tratament, test ABAB design Test, tratament, test, tratament Design serial n timp Stabilete o linie de baz ncepe tratamentul Msoar rezultatele tratamentului Design cu linii de baz multiple Obine un numr de linii de baz diferite Fiecare linie de baz trebuie s fie independent de altele Trateaz doar o variabil odat

Instrumente de colectare a datelor

Cerine Fiabilitate Valide Sensibilitate Universale Fr erori

Instrumente de colectare a datelor

Ce inseamn fiabilitate?
Instrumentul va putea msura cu aceeai acuratee: n situaii diferite de testare?
Testeaz - retesteaz fiabilitatea

Experimentatori diferii?
Fiablitate Inter - operator

Instrumente de colectare a datelor

Este valid?
Instrumentul care va fi folosit poate msura datele pe care le dorim?

Instrumente de colectare a datelor

Este Sensibil?
Instrumentul ar trebui sa fie la fel de sensibil indiferent de prezenta sau nu a variabilei msurate i de cantitatea acesteia (linearitate).
Trebuie sa se caracterizeze valorile: Fals-pozitivi: Subiectii sanatosi, prezentati ca bolnavi. Fals-negativi: Subiecii bolnavi, prezentai ca sanatosi.

Instrumente de colectare a datelor

Este universal?
Investigatorul ar trebui sa foloseasc un instrument larg aplicat care sa ajute la compararea datelor i diminuarea erorilor de raportare, pentru a face posibila compararea cu date din literatura.

Instrumente de colectare a datelor

Este fara erori?

Ar trebui sa nu existe diferene intre valoarea reala i valoarea pe care un investigator o obine prin msurare altele dect diferente date de variabilitatea de eantionare.

Metode de colectare
1. Colectare Randomizata (Simpla)
2. Colectare Sistematica

3. Colectare Stratificata
4. Colectare pe grupe / segmente

5. Colectare pe alte criterii

6. Alte tipuri de colectare

Variabile Calitative i Cantitative

Exemple de variabile calitative sunt ocupatia, sexul, status marital, etc. Variabilele care permit cuantificarea i care pot fi msurate sunt considerate variabile cantitative. Exemple de variabile cantitative sunt greutatea, naltimea, vrsta. Variabilele cantitative pot fi clasificate ca discrete sau continue

Tipuri de variabile

1.

Variabile de tip categorii (e.g., Sex, Status Marital, religie, naionalitate, profesie) Variabile de tip continuu (e.g., vrsta, venit, greutate, inaltime) Variabile discrete (e.g., Numar de copii) Variabile Binare sau Dihotomice (e.g., ntrebri la care se da raspuns prin Da sau Nu)

2.

3. 4.

Scale de Date
1. Nominale: Aceste date nu reprezint o cantitate (e.g., Status Marital, Sex)
2. Ordinale: Aceste date reprezint o serie ordonata de elemente interrelaionate (e.g., nivelul de educatie) 3. Interval: Aceste date reprezint o cantitate msurata pe un scala de interval avnd un numr egal de uniti i un punct zero arbitrar. (e.g.: Temperatura in Celsius) 4. Raport : Variabile, cum este greutatea pentru care putem compara semnificatia uneia fata de cealalta (, 100 Kg este dublul a 50 Kg)

Variabile din protocol TIPURI de VARIABLE

independente dependente intermediare De confuzie

Variabila Independent
O caracteristica pentru care se face o msurtoare i/sau observaie, care influeneaz un eveniment sau rezultat (variabila dependenta).
NOTA Variabila independenta nu este influenat de eveniment sau rezultat, dar o poate determina sau contribui la variaia sa.

Variabila Dependent
O variabil a crei valoare este dependent de efectul altor variabile (variabile independente) in raportul de cauzalitate studiat. Sinonime: variabila rezultat sau rspuns.
NOT

Un eveniment sau rezultat a crui variatie ncercam sa o explicam prin influenta variabilelor independente.

Variabile Intermediare
O variabila care apare intr-o relaie de cauzalitate de la o variabila independenta la o variabila dependenta. Sinonime: intervenie, mediere NOTE produce variaii in variabila dependenta i variaz datorita variabilei independente. O asemenea variabila este asociata att cu variabila dependenta cat i cu variabila independenta.

Variabile de confuzie
Un factor (care este el insusi determinant al rezultatului), care perturba efectul aparent al unei variabile de studiu asupra rezultatului. NOTA Un asemenea factor poate fi distribuit inegal intre cei expui i neexpui i astfel influeneaz magnitudinea aparenta i chiar direcia efectului.

Organizarea Datelor

1. Tabel de frecventa 2. Histograma de frecventa 3. Histograma de frecventa relativa 4. Histograma 5. Poligon de frecventa 6. Poligon de frecventa relativa 7. Grafic cu coloane 8. Grafic placinta 9. Tabel Trunchi cu ramuri 10.Box plot

Tabel de frecventa
Suppose we are interested in studying the number of children in the families living in a community. The following data has been collected based on a random sample of n = 30 families from the community. 2, 2, 5, 3, 0, 1, 3, 2, 3, 4, 1, 3, 4, 5, 7, 3, 2, 4, 1, 0, 5, 8, 6, 5, 4 , 2, 4, 4, 7, 6 Organize this data in a Frequency Table!

Tabel de frecventa
X=No. of Children Count (Freq.)
0 1 2 3 2 3 5 5

Relative Freq.
2/30=0.067 3/30=0.100 5/30=0.167 5/30=0.167

4
5 6 7 8

6
4 2 2 1

6/30=0.200
4/30=0.133 2/30=0.067 2/30=0.067 1/30=0.033

Grafic de frecventa
6 5 4 3 2 1 0 0 1 2 3 4 5 6 7 8 Freq.

Tabel de frecventa

Now suppose we need to construct a similar frequency table for the age of patients with Heart related problems in a clinic. The following data has been collected based on a random sample of n = 30 patients who went to the emergency room of the clinic for Heart related problems. The measurements are: 42, 38, 51, 53, 40, 68, 62, 36, 32, 45, 51, 67, 53, 59, 47, 63, 52, 64, 61, 43, 56, 58, 66, 54, 56, 52, 40, 55, 72, 69.

Tabel de frecventa
Age Groups Frequency Relative Frequency
2/30=0.067

32 -36.99

37- 41.99
42-46.99 47-51.99 52-56.99 57-61.99 62-66.99 67-72 Total

3
4 3 8 3 4 3 n=30

3/30=0.100
4/30=0.134 3/30=0.100 8/30=0.267 3/30=0.100 4/30=0.134 3/30=0.100 1.00

Msurarea tendinei centrale

Unde este centrul distributiei? 1. Media 2. Mediana 3. Modulul

Empiric
For a Normal distribution approximately,

a) 68% of the measurements fall within one standard deviation around the mean
b) 95% of the measurements fall within two standard deviations around the mean c) 99.7% of the measurements fall within three standard deviations around the mean

Concepte necesare

Scale de msura Distribuie, tendina centrala, variabilitate, probabilitate Prevalenta i incidenta bolilor Rezultate ale bolilor (mortalitate, morbiditate) Asocieri (corelaie sau covariana) Impact asupra sanatatii (diferene de risc i rapoarte) Sensibilitate, specificitate, valoare predictiva

Scale

Nominal qualitative classification of equal value: gender, race, color, city Ordinal - qualitative classification which can be rank ordered: socioeconomic status of families Interval - Numerical or quantitative data: can be rank ordered and sizes compared : temperature Ratio - interval data with absolute zero value: time or space

Distribuie, Tendina centrala

Mean

Variabilitate, Probabilitate
Mean Median Mode Standard deviation Statistical Significance p < .01

Interval de ncredere

Semnificaia statistica - erori

Null Hypothesis = Ho
Ho True Reject Ho Type I error Ho False Correct decision

Do Not Reject Ho

Correct decision

Type II error

Manual statistic Online

The Statistics Homepage
http://www.statsoftinc.com/textbook/stathome.html

Prevalena i Incidena
Prevalence

probability of disease in entire population at any point in time 2% of the population has diabetes probability that patient without disease develops disease during interval 0.2% or 2 per 1000 new cases per year

Incidence

Sensibilitate, Specificitate
sensitivity = a / (a+c) specificity = d / (b+d)
Patients with disease
Test is positive Test is negative

Patients without disease

a c

b d

Valoare Predictiva
Positive predictive
value = a / ( a+b)

Patients with disease Test is positive

Test is negative

Patients without disease

Negative predictive
value = d / (c+d) Post-test probability of disease given positive test = a / (a+b) Post-test probability of disease given negative test = c / (c+d)

a
c

b
d

Resurse
An Introduction
http://www.poems.msu.edu/InfoMastery/default.htm

Diagnosis
Sensitivity and specificity Predictive values Likelihood ratios

InfoRetriever

Calculators: Epidemiology, Diagnostic test

Eroarea n trialuri clinice

Areas in which bias can occur
Systematic error in . . . Allocation Response Assessment

Eroarea n trialuri clinice

Allocation or Susceptibility Bias
Can occur when patient assignments to a trial group are influenced by an investigators knowledge of the treatment to be received.

Can result in treatment groups that have different prognoses.

Eroarea n trialuri clinice

Allocation or Susceptibility Bias
Treatment groups must have similar prognoses, which is achieved by:

Randomization of patients Prospective evaluation of patients Well-defined inclusion and exclusion criteria

Randomizarea n trialuri clinice

Occurs when patients are assigned to treatments by means of a mechanism that prevents both the patients and the investigator from knowing which treatment is being assigned.

Beneficiile Randomizarii
Prevents the systematic introduction of bias.
Minimizes the possibility of allocation bias.

Balances prognostic factors for treatment

groups. Improves the validity of statistical tests used to compare treatments.

Eroarea n trialuri clinice

Response & Assessment/Recording Bias
Can occur when a patient reports a treatment response or when an investigator assesses that responseeither person can be influenced by knowing the treatment. A patient or an investigator may have a preconceived idea of which treatment is better. The patient may also want to please the investigator.

Eroarea n trialuri clinice

Blinding
To minimize Response & Assessment/Recording Bias

Single Blind (patient blinded): protects against response bias.

Double Blind (patient and investigator blinded): protects against assessment/recording bias as well as response bias.

Eroarea n trialuri clinice

Transfer bias Occurs when patients are lost to follow-up. Must be minimized. Performance bias Can occur with a single surgeon or with multiple surgeons.

Confuzia - factori
Relationship between coffee and pancreatic cancer, BUT Smoking is a known risk factor for pancreatic cancer Smoking is associated with coffee drinking but it is not a result of coffee drinking.

Detectarea confuziei
If an association is observed between coffee drinking and pancreatic cancer

Coffee actually causes pancreatic cancer, or The coffee drinking and pancreatic cancer association is the result of confounding by cigarette smoking.

Evaluarea confuziei
If you know something is a possible confounder, in the data analysis use

Stratification, or Adjustment

Fear the unknown!

Taxonomia designului de studii

Treatment vs. Observational Prospective vs. Retrospective Longitudinal vs. Cross-sectional
Randomized vs. Non-Randomized Blinded/Masked or Not Single-blind, Double blind, Unblinded

Randomizarea
Random allocation

known chance receiving a treatment cannot predict the treatment to be given

Eliminate selection bias Similar treatment groups

Un factor Var. Ind.

Randomization tries to ensure that ONE factor is different between two or more groups. Observe the Consequences Attribute Causality

Tipuri de randomizare
Standard ways: Random number tables Computer programs NOT legitimate Birth date Last digit of the medical record number Odd/even room number

Tipuri de randomizare
Simple Blocked Randomization Stratified Randomization

Randomizare simpla
Randomize each patient to a treatment with a known probability

Corresponds to flipping a coin

Could have imbalance in # / group or trends in group assignment Could have different distributions of a trait like gender in the two arms

Randomizare n bloc
Insure the # of patients assigned to each treatment is not far out of balance Variable block size

An additional layer of blindness

Different distributions of a trait like gender in the two arms possible

Randomizare stratificata
A priori certain factors likely important (e.g. Age, Gender) Randomize so different levels of the factor are balanced between treatment groups Cannot evaluate the stratification variable

Randomizare stratificata
For each subgroup or strata perform a separate block randomization Common strata

Clinical center, Age, Gender

Stratification MUST be taken into account in the data analysis!

Rezultat
Introductory Statistical Definitions What is Randomization? Randomized Study Design Experimental vs. Observational Non-Randomized Study Design Stat Software, Books, Articles

Tipuri de studii randomizate

Parallel Group Sequential Trials Group Sequential trials Cross-over Factorial Designs

Grup paralel
Randomize patients to one of k treatments Response

Measure at end of study Delta or % change from baseline Repeated measures Function of multiple measures

Studiul Ideal - Gold Standard

Double blind Randomized Parallel groups

2 studii
Study 1

A U.S. study (2000) compared 469 patients with brain cancer to 422 patients who did not have brain cancer. The patients cell phone use was measured using a questionnaire. The two groups use of cell phones was similar.

Study 2

An Australian study (1997) conducted a study with 200 transgenic mice. One hundred were exposed for two 30 minute periods a day to the same kind of microwaves with roughly the same power as the kind transmitted from a cell phone. The other 100 mice were not exposed. After 18 months, the brain tumor rate for the exposed mice was twice as high as that for the unexposed mice.

Diferente?
How do the two studies differ?

Study 1

Study 2

?
Why do the results of different medical studies sometimes disagree?

Could the second study be performed on human beings?

Evaluarea faptelor
Suppose a friend recently diagnosed with brain cancer was a frequent cell phone user. Is this strong evidence that frequent cell phone use increases the likelihood of getting brain cancer?

Informal observations of this type are called _____________ _____________. You should rely on reputable research studies, not anecdotes.

Cum putem obine informaii

Observational Study

The researcher observes values of the response and explanatory variables for the sampled subjects without imposing any treatments Example: The researcher assigns experimental conditions (also called treatments) to subjects (also called experimental units) and then observes outcomes on the response variable. Treatments correspond to values of the explanatory variable Example:

Experiment

Tipuri de studii observationale

Retrospective

Observational studies that look back in time

This is sometimes done to find risk factors for certain diseases

Cross-Sectional

Observational studies that take a cross section of the population at the current time Observational studies in which subjects are followed into the future

Prospective

Studii Experimentale / Observaionale

In an observational study, there can always be confusion variables affecting the results. This means that observational studies can _________ show causation. It is easier to adjust for confusion variables in an experiment. In general, we can study the effect of an explanatory variable on a response variable more accurately with an experiment than with an observational study.

Dezavantaje ale Experimentului

They can be ____________ to perform on the subjects in which you are interested. It can be difficult to monitor subjects to ensure that they are doing what they are told. They can take many years, even decades, to complete. Results of experiments that use animals do not ______________ to humans. They are unnecessary the question of interest does not involve trying to assess _____________.

Design al colectrii datelor pentru studii observaionale

Simple Random Sampling (SRS)

A simple random sample of n subjects from a population is one in which each possible sample of that size has the _______ chance of being selected.

Colectarea datelor n studii observaionale

Stratified Sampling

A stratified random sample divides the population into separate groups, called ________, and then selects an SRS from each stratum.

Colectarea datelor n studii observaionale

Cluster Sampling

A cluster random sample can be used if the target population naturally divides into groups, each of which is representative of the entire target population. In this method, a SRS of groups (or strata) is taken. Every member of the selected groups is put into the sample.

Colectarea datelor n studii observaionale

Systematic Sampling

A systematic sample selects every kth person from the sample frame. The researcher randomly selects a number between 1 and k in order to know which person to select first, then selects every kth person after this.

Avantaje ale colectrii

Simple Random Sampling (SRS)

It is the easiest most widespread form of sampling. Each subject has an _______ chance to be in the sample. The sample enables us to determine how likely it is that descriptive statistics (like the sample mean) fall close to corresponding values for which we would like to make inference (like the population mean).

Avantaje ale colectrii

Stratified Sampling

It ensures that there are enough _________ in each group that you want to compare. It does not require a sampling frame of subjects. It is less ___________ to implement.

Cluster Sampling

Eroarea n colectarea datelor

A sampling method is _________ if

The sample tends to favor some parts of the population over others. In other words, the results from the sample are not representative of the population.

Obviously, __________ samples are our goal.

Tipuri de erori
Undercoverage

Occurs when a sampling frame leaves out some groups in the population

Nonresponse bias

Occurs when some sampled subjects cannot be reached, refuse to participate or fail to answer some questions
Occurs when the subject gives an incorrect response or when the question wording or the way the interviewer asks the questions is confusing or misleading

Response bias

Elemente pentru un studiu corect

Control group

Gives us something to compare against Enables us to control the __________ _______

The placebo effect occurs when patients seem to improve regardless of the treatment they receive.

Randomization

Eliminates ______ that can result when researchers assign treatments to the subjects Balances the group on variables that you know affect the response Balances the group on _________ variables that may be unknown to you

Elemente pentru un studiu corect

Blinding

Increases reliability of the results

_________-blind: subjects do not know the treatment assignment _________-blind: neither the subjects nor those in contact with the subjects know the treatment assignment

Exemplu
A pharmaceutical company has developed a new drug for treating high blood pressure. To determine the effectiveness of the drug, the company conducted an experiment in which subjects with a history of high blood pressure were treated with the new drug.
A later experiment randomly divided subjects with a history of high blood pressure into two groups. Group A was treated with the new drug as before. Group B received the most popular drug on the market at that time. The subjects were unaware of which treatment they received. 60% of the patients in Group A improved, while 63% of the patients in Group B improved. The __________ experiment is better because

Exemplu
To investigate whether antidepressants help smokers to quit smoking, one study used 429 men and women who were 18 or older and had smoked 15 cigarettes or more per day in the previous year. They were all highly motivated to quit and in good health. They were assigned to one of two groups: one group took an antidepressant called Zyban, while the other group did not take anything. At the end of a year, the study observed whether each subject had successfully abstained from smoking.

Studii comparative randomizate

Randomization ensures that the groups of subjects are similar in all respects before the treatments are applied. Using a control group for comparison ensures that external influences operate equally on both groups. If the groups are large enough, natural differences in subjects will average out. This means that there be little difference in the results for the groups unless the treatments themselves actually cause the difference.

Studii i erori

Types of studies: Observational studies and experiments Experiments control for lurking variables Sampling designs: SRS, stratified random samples and cluster samples SRS is the preferred method Potential sources of bias: Undercoverage Response bias Nonresponse bias Convenience sampling Voluntary response sampling Elements of good experiments: Control group, randomization and blinding

Precauii
If a group is underrepresented in the sample, we cannot make inference about it.
We must be careful when interpreting the results of observational studies. For comparison of several treatments to be valid, you must apply all treatments to similar groups of experimental units. Interesting questions are usually pretty tough to answer. This is due in part to the fact that no single experiment or observational study can determine causation.

Stop and Think!!!

Write the study! Describe & classify the variables. Instruments for measure? Bias?

Prepare to analyze data!