Developing an effective recruitment strategy

Riccardo Belli, MD Email contact: riccardo_belli@yahoo.it

A warning
Opinion expressed in this presentation are those of the Author and not necessarily those of the representative Company

Subject recruitment importance

86% of all clinical trials fail to recruit the required number of subjects on time with 52% delayed by one to six months 1 clinical trials last 42% longer than expected in Phase I, 31% longer in Phase II, and 30% beyond planned deadlines in Phase IIIall because of recruitment delays 2 85%95% of all days lost during clinical trials are due to a failure to recruit subjects on time 3 Each day a drug is delayed from market, sponsors lose up to $8 million 3

1. 2. 3.

Mary Jo Lamberti Enrollment Delays are Getting Worse, in An Industry in Evolution, 4th ed., Ed. (Thomson CenterWatch, Boston, 2003), 79. Cutting Edge Information, "Accelerating Clinical Trials: Budgets, Patient Recruitment, and Productivity," May 2004 J. Cruz Rowe, M.E. Elling, J.G. Hazlewood, R. Zakhary, A Cure for Clinical Trials, The McKinsey Quarterly, (2) 134 141 (2002).

Critical key player in the recruitment process

Investigators Subjects Protocol Environment

Investigators Importance on recruitment process

They add credibility and medical expertise in the clinical area and mediate the study discussion They have access to information pertaining to subjects whose characteristics are more appropriate to the study conducted They have daily exposure to potential subjects and are able to introduce information about the trial and ask for their participation during these visits.

Investigators Aspects with negative impact on recruitment 1,2

Logistical aspects

Lack of time (workload) Lack of resources and training Unstable research team Overestimation of the available study population
Concern for the patients A lack of interest in the research question Concern for the effect on the investigatorpatient relationship Concern for potential loss of clinical autonomy An inability to deal with conflicting roles

Personal aspects

1. 2.

Missconception and lack of awareness greately reduce recruitment for cancer clinical trial http://www.harrisinteractive.com./news2001Vol1_iss3.pdf J. Sullivan, "Subject Recruitment and Retention: Barriers to Success," Applied Clinical Trials, 14 (4) (April 2004).

Investigators Aspects with positive impact on recruitment 1,2,3

Personal aspects
Scientific interest Patient benefits
Dissatisfaction with current therapies Desire to provide leading-edge care to their patients Providing access to treatment, tests, and services that are not reimbursed or available

Scientific immediacy
Regular communication about results and recruitment status

Financial compensation Relationship with the Sponsor and CRO

1. 2. 3.

Missconception and lack of awareness greately reduce recruitment for cancer clinical trial http://www.harrisinteractive.com./news2001Vol1_iss3.pdf J. Sullivan, "Subject Recruitment and Retention: Barriers to Success," Applied Clinical Trials, 14 (4) (April 2004). Jefferies & Company, Contract Research Industry Comprehensive Update: Can CROs Outperform Their Customers Again? Pharmaceutical Services Quarterly Preview, January 19, 2005

Investigators Strategy to improve recruitment aspects

Investigator and Site selection Investigator and Site performance Communication between Investigator and the Sponsor

Investigator and Site selection

Adequate sources information
Company and Affiliates colleagues feedback Refferral Investigator feedback Library Database (eg. Pubmed, Scopus) Intelligence service (eg. SiteTrove, TrialTrove) Clinical trial Register Database (eg. international and national database clinical trial registry) Qualified CRO feedback Professional Network

Investigator and Site selection

Proved scientific interest in related field (eg. pediatric infection disease treatment and prevention) Previous attested experience in clinical trial sponsored by pharmaceutical company Access and estimation to the appropriate subject population
Evaluate previous recruitment performance with similar population Understanding the frequency with which investigator see the desired subjects Provide a realistic recruitment plan Provide a detailed subject source mapping

Investigator and Site selection

Adequate resources and training
Adequate staff and facilities for recruitment potential

Compliance with GCP and applicable regulatory requirement

Previous internal audit Previous inspection from Competent Authority Feedback from national or international Clinical Investigator Inspection List

EC approval and contract finalization achived in a reasonable timeframe

Investigator and Site performance

Costant monitoring of adequate resources presence and training during the trial
Estimate study staff turnover Guarantee a costant training and monitoring the site before and during the trial

Management of the site workload

Limit at the essential the complexity of the study process Site could hire for a temporary period a clinical site coordinator to support data entry and recruitment

Investigator and Site performance

Promote the investigator scientific interest
Involve the investigator in the protocol procedure development and country study feasibility process Collaborate with Medical Affair in the way to make the investigator clinical activity evident

Optimize financial compensation

Have a current overview about the fees applied by other companies in certain area Establish the best fee according to the protocol complexity and staff workload (es. EDC, number of visits, blood drawn)

Investigator and Site performance

Involve the investigator in the study information loop
Costant comunication with the investigators about the study performance and analisys results PeriodicaIly inform all the study investigators about the recruitment status by site and by country in the way to aliment a positive competitive recruitment environment Promote an investigator expert networking

Optimize the recruitment process

Collaborate with the investigator for the creation of a detailed and realistic site recruitment procedure plan Define a correct communication plan Include the recruitment in the risk management plan process

Investigator and Site performance

Define a correct Information Flow
Define each role and the responsability at site study staff and Sponsor level (es. define staff accountable for recruitment) The Sponsor should establish strong communication with the reference study staff involved in the enrollment process, in order to expedite decisions and the recruitment progress between the Sponsor and recruitment consultants Periodic teleconference to discuss performance versus recruitment plan

Subjects Importance on recruitment process

Pivotal role as the most important partner in the clinical research process

Subjects Aspects with negative impact on recruitment 1,2

Logistic and economic aspects
Travel distance Travel costs Cost not covered by insurance (eg. in US)

Demographic aspects
Age Level of education Language Cultural issue Social circumstances (lack time to attend extra trial-related appointments due to family commitments) Attitude of family members (elderly may be reluctant to participate in a clinical trial due to family objections )
1. 2. Missconception and lack of awareness greately reduce recruitment for cancer clinical trial http://www.harrisinteractive.com./news2001Vol1_iss3.pdf J. Sullivan, "Subject Recruitment and Retention: Barriers to Success," Applied Clinical Trials, 14 (4) (April 2004).

Subjects Aspects with negative impact on recruitment 1,2

Subjects attitude to the clinical trial
Uncertainty of the therapy Lack of information about clinical trial benefit Guinea Pig syndrome The additional demands associated with trial participation Effort involved in informed consent process

Subjects attitude to the trial design

Treatment schedule Study timing (visit numbers and timing windows, partecipation period) Fear placebo rather than active treatment

1. 2.

Missconception and lack of awareness greately reduce recruitment for cancer clinical trial http://www.harrisinteractive.com./news2001Vol1_iss3.pdf J. Sullivan, "Subject Recruitment and Retention: Barriers to Success," Applied Clinical Trials, 14 (4) (April 2004).

Subjects Aspects with negative impact on recruitment 1,2

Disease related aspects
Subjects disease status

Personal dinamic of the subject

Subjects tending to change jobs more frequently and are moving to new locations to take up these jobs

1. 2.

Missconception and lack of awareness greately reduce recruitment for cancer clinical trial http://www.harrisinteractive.com./news2001Vol1_iss3.pdf J. Sullivan, "Subject Recruitment and Retention: Barriers to Success," Applied Clinical Trials, 14 (4) (April 2004).

Subjects Aspects with positive impact on recruitment 1

Positive experience reported by subjects in clinical trials
High rate of quality care Obtain faster access to treatment Dignity and respect Not subjected to more tests and procedures than they thought necessary Not treated like Guinea Pig subjects who participated in clinical studies would do so again

Most of public believe it is essential or very important that all new pharmaceutical products be tested on humans before they are approved for general use

1. Missconception and lack of awareness greately reduce recruitment for cancer clinical trial http://www.harrisinteractive.com./news2001Vol1_iss3.pdf

Strategy to improve Subjects related recruitment aspects

Good comunication skills Site facilities and procedure Logistic support

Good comunication skills

Subjects need to be informed and understand what partecipation in clinical trial can potentially offer them and help to turn those who are somewhat confident into very confident
How their clinical trials is designed (goal and requirements) What is hoped to be gained by their partecipation Informed of the risk and benefit Protection available for them as subjects regarding costs, privacy and right Such reassurance is hindered by the fact that so few protocol developers are able to write consent documents that comply with the directive in 21 CFR 50.20 thus Putting technical medical terms into easily understood language is a rare art form

Good comunication skills

Site Staff good comunication skills
Site staff who will be screening and interviewing potential subjects and obtaining informed consent skilled at verbal communications and responding to subjects questions and concerns
Organize site staff training providing also informative material (eg. Distribute FAQ from site and subjects)

Site staff focused on creating a pleasant customer service experience for the subject
Spending time talking and listening, offering information, and giving subjects time to express their experiences and ask questions Welcoming subjects, valuing their experience, responding to their suggestions and respecting subjects as partners in the clinical research process

Good comunication skills

Sponsor good comunication skills
Organize ad hoc training session with expert to further improve comunication skills Working together with site staff could contribute to further improve the readibility of the informed consent and other documents in simple language and structure Provide written educational materials to read and resources about the informed consent process as well as specifics about the study Expressing appreciation for volunteer time and commitment helps reinforce the participants experience of contributing to science and increases their trust in the clinical research enterprise

Good comunication skills

Site facilities and procedure to be in compliance with subjects expectations (to be check during pre-study visits)
Subject-friendly facilities
Comfortable waiting room General appearance (e.g. surroundings, atmosphere, parking, arrival)

Efficient appointment scheduling Adaptation of clinic staff to accommodate subjects work schedules Type of screening procedures (clinical chart review, phone, mail, face to face)

Logistic support
Cover subject expenses
Travel cost support

Protocol Aspects with negative impact on recruitment

The Study design Data collection requirements Inclusion and exclusion criteria Incompatibility of the protocol procedures with usual clinical practice Disagreement with the protocol by some investigators An investigators lack of full support and enthusiasm for an aspect of the study

1.

J. Sullivan, "Subject Recruitment and Retention: Barriers to Success," Applied Clinical Trials, 14 (4) (April 2004).

Sponsor strategy to improve protocol related recruitment aspect

Obtain secure input from the sites on protocol and study related documents (eg. diary card, worksheet) and procedure
Made the protocol as an opportunity for the subject
Guarantee the best supportive care and treatment according to the local requirement Evaluate a protocol strategy to overcome weakness related to placebo

Inclusion and exclusion criteria

Compliance with the disease or condition being studied

Concomitant medication
Compliance with the local schedule and requirements

Medical procedure and treatments

Compliance with the standard medical practice

Visit schedule
Compliance in terms of visit frequency and duration

Environment Aspects with negative impact on recruitment

Although the subjects population in general may be the same age and be suffering from the same conditions as required by the study, each potential subject is unique in terms of his or her interests, needs, motivations, and habits and is part of a particular cultural environment Each site is structured differently, operates in different environments, personnel and needs

1.

Lars-Olof Eriksson , Beth D. Harper, Successful Subject Recruitment: One Size Does Not Fit All, Applied Clinical Trials 14 (1) November 1, 2002

Strategy to improve environmental related recruitment aspects

Elaborate ad hoc risk analisys taking in consideration the whole local environmental aspects
Organize specific feasibility assessment at country/district level involving internal and external stakeholder with previous experience in the area
Company and Affiliates colleagues CRO Referral investigators

Conclusion
Selecting the most appropriate and cost-effective approach to reaching potential subject populations is complex and multifaceted Establish a good comunication between subjects, investigators and Sponsor is important for improving the recruitment process Understanding and avoiding common mismatches between the protocol design, site infrastructure, and prospective subjects interests and needs will make recruitment easier Successful recruitment requires sensitivity to site, geographic, cultural, and community differences and a willingness to tailor the recruitment program, where possible, to accommodate these differences