Post on 30-Nov-2014
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 III—all 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. Mary Jo Lamberti ―Enrollment Delays are Getting Worse,‖ in An Industry in Evolution, 4th ed., Ed. (Thomson
CenterWatch, Boston, 2003), 79.
2. Cutting Edge Information, "Accelerating Clinical Trials: Budgets, Patient Recruitment, and Productivity," May 2004
3. 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.
InvestigatorsAspects 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
Personal aspects
– Concern for the patients
– A lack of interest in the research question
– Concern for the effect on the investigator–patient relationship
– Concern for potential loss of clinical autonomy
– An inability to deal with conflicting roles
1. Missconception and lack of awareness greately reduce recruitment for cancer clinical trial
http://www.harrisinteractive.com./news2001Vol1_iss3.pdf
2. J. Sullivan, "Subject Recruitment and Retention: Barriers to Success," Applied Clinical Trials, 14 (4) (April 2004).
InvestigatorsAspects 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. Missconception and lack of awareness greately reduce recruitment for cancer clinical trial
http://www.harrisinteractive.com./news2001Vol1_iss3.pdf
2. J. Sullivan, "Subject Recruitment and Retention: Barriers to Success," Applied Clinical Trials, 14 (4) (April 2004).
3. Jefferies & Company, Contract Research Industry Comprehensive Update: Can CROs Outperform Their Customers
Again? Pharmaceutical Services Quarterly Preview, January 19, 2005
InvestigatorsStrategy 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. Missconception and lack of awareness greately reduce recruitment for cancer clinical trial
http://www.harrisinteractive.com./news2001Vol1_iss3.pdf
2. 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. Missconception and lack of awareness greately reduce recruitment for cancer clinical trial
http://www.harrisinteractive.com./news2001Vol1_iss3.pdf
2. 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. Missconception and lack of awareness greately reduce recruitment for cancer clinical trial
http://www.harrisinteractive.com./news2001Vol1_iss3.pdf
2. 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 investigator’s 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