Recruitment of Human Research Subjects in Clinical Research

1
Recruitment of Human Research Subjects in
Clinical Research

• Introduction A systematic approach to subject
  recruitment and the evaluation of effective
  performance methods as well as the total success
  of the clinical research program.

2
Recruitment

• Barriers and Challenges
• Patient attitudes community standards,
  individual psychosocial factors about healthcare
  research, and negative publicity
• Provider attitudes pressure from sponsor to
  recruit, inclusion/exclusion criteria, uneven
  recruitment planning
• Sponsor attitudes unaware of research subject
  attitudes, pressure to develop new drugs in a
  timely and cost effective manner
• Ethical contradications in the context of
  sponsoring, monitoring, and evaluating a clinical
  research program
• Inclusion/exclusion criteria
• Catch as catch can

3
RecruitmentNot an easy road

• Wide concerns from FDA and DHHA
• Growing concern over clinical trial recruitment
  strategies and tactics for ensuring adequate
  enrollment and retention
• DHHS, Office of Inspector General Report, June
  2000, two part report
• Public perception fueled by lay press, New York
  Times, Seattle Times, USA Today, LA Times

4
Recruitment

• Patient (human research subject) attitudes.
• Growing concern about their safety and how well
  they will be protected from research risks
  (perception is reality)
• Newspaper articles
• 1999 fifty articles that cast a shadow of doubt
  (including research-related deaths) over the
  clinical trial industry
• See attached email dated April 28, 30, 2001

5
Recruitment

• Financial Facts about research subject
  recruitment
• Inadequate planning results in
• 25 delays in new drug development programs
• Average cost to recruit consumes 15 of budget
• Of 163 Phase III clinical trials, 78 of sites
  missed enrollment deadlines
• Average cost to recruit/enroll ranges from 1300
  to 2400, depends on complexity of trial

6
RecruitmentWhat the Sponsor needs to know

• Pre Study Questionnaire (enrollment metrics)
• What was the name of the study and what was the
  indication?
• What was the expected number of subjects to be
  enrolled at site?
• What was the actual number of subjects screened
  at site and over what period of time?
• How long (in months) did it take your site to
  reach enrollment?
• How many patients did you complete?

7
RecruitmentOne of the most critical elements

• Identifying, Recruiting, Enrolling patients is
  the most challenging part of any clinical trial
• Participation rates are low 3 to 20 of
  potential subjects who are screened
• Oncology patients enroll in clinical trials 8
  of the time

8
RecruitmentThe stark reality

• Survey of oncology patients (Harris Feb 2001)
• 5972 cancer patients surveyed about clinical
  trials
• 85 unaware or unsure that participating in
  clinical trials was a treatment option
• 75 said they would have been willing to
  participate
• 33 said they would be better off taking standard
  treatment
• 29 feared they would receive placebo
• 20 feared they would be treated like guinea
  pigs
• 18 feared doctor would not be able to choose
  best treatment

9
Recruitment

• Survey of patients without cancer
• Number in patient base not quoted in survey
• 82 would consider enrolling
• 56 feared receiving a placebo
• 47 feared they would lose autonomy and decision
  making ability
• 44 feared being treated like a guinea pig

10
RecruitmentThings are never as they appear

• Recruitment flaws are the leading cause of
  clinical research failure
• Lasagnas Law (Louis Lasagna, Tufts University)
• Muenchs Postulates, Laws and Corollaries
• Investigators overestimate the pool of available
  patients who meet inclusion criteria that are
  willing to participate in clinical research.

11
Recruitment

• Funnel Effect of recruiting research subjects
  dwindling returns when screening
• Illustrates the progressive shrinking of the
  research subject population prior to enrollment
• Usually related to the clinical trial
• End result is the number of research subjects who
  enter the clinical trial

12
Recruitment

• Illustration of the Funnel Effect
• 8027 research subjects screened
• 3103 unavailable during key hours
• 4254 preliminary exclusion
• 21 not screened for various reasons
• 258 rejected prior to interview
• 53 rejected after interview
• 92 not consenting
• 146 not medicated
• 100 research subjects enrolled

13
Recruitment

• Why do all clinical investigators overestimate
  patient recruitment?
• Inclusion criteria seriously restricts
  availability insufficient time reviewing
• They are naïve to clinical research
• Do not adequately consider the patients
  willingness to comply with the trial
• Do not understand the patients interests and
  motivations in the treatment being tested

14
Recruitment

• Stages of research subject recruitment
• Pre-screening research subjects
• Develop a recruitment strategy
• Develop a plan to contact or reach patients
• Contact referral groups
• Utilize advertising medica (IRB approval needed)
  integrate into your budget
• Carefully review your patient database against
  the inclusion and exclusion criteria
• Is this study compatible with the practice
  population

15
Recruitment

• Stages of subject recruitment
• Screening of research subjects
• Discuss the clinical trial with the prospective
  research subject
• Assess the patients initial interest based on
  study requirements and scheduling
• Conduct initial screening questions using
  inclusion/exclusion as guide, use checklist, part
  of source documents
• Conduct initial history, physical, and clinical
  laboratory screen (also special laboratories)
• Re-screen or conduct a more detailed secondary
  screen to confirm labs, ask detailed questions,
  schedule additional tests
• Obtain patients informed consent

16
Recruitment

• Recruitment ? Compliance ? Retention
• What motivates the patient to participate in a
  clinical trial?
• Access to promising therapies
• Access to greater medical expertise
• Close ? Individualized medical attention/care
• Emotional support
• Something to do (break boredom)
• Altruism (usually limited to Phase I)

17
Recruitment

• Recruitment ? Compliance ? Retention
• What are some of the concerns patients have about
  participating in clinical research? Will the drug
  and trial be safe?
• What if I change my mind and decide to drop out?
• Will I get a placebo or the real thing?
• Whats in it for me?
• Will I be taken advantage of?
• Whats in it for my doctor?

18
RecruitmentGuidance on Advertising

• Regulations 21 CFR 50.20, 50.25, 56.111(a)(3)
  and 812.20(b)(11)
• Do not specifically address language and tone of
  advertising
• FDA Guidance Sheets FDA Information Sheets
  Guidance for IRBs and Clinical Investigators
• Does provide sound advice

19
RecruitmentGuidance on Advertising

• FDA Information Sheets Guidance for IRBs and
  Clinical Investigators
• the procedure for recruiting subjects is not
  coercive and does not state or imply a certainty
  of favorable outcome or other benefit beyond what
  is outlined in the consent document and protocol.

20
RecruitmentGuidance on Advertising

• FDA Information Sheets Guidance for IRBs and
  Clinical Investigators
• No claims should be made, either explicitly or
  implicitly, that the drug, biologic or device is
  safe or effective for the purpose under
  investigation

21
RecruitmentGuidance on Advertising

• FDA Information Sheets Guidance for IRBs and
  Clinical Investigators
• Advertising for recruitment into
  investigational drug, biologic or device studies
  should not use terms such as new treatment,
  new medication or new drug without explaining
  that the test article is investigational. A
  phrase such as receive new treatments implies
  that all study subjects will be receiving newly
  marketed products of proven worth.

22
RecruitmentGuidance on Advertising

• FDA Information Sheets Guidance for IRBs and
  Clinical Investigators
• Advertisements should not promise free medical
  treatment, when the intent is only to say (the)
  subject will not be charged for taking part in
  the investigation.

23
RecruitmentGuidance on Advertising

• FDA Information Sheets Guidance for IRBs and
  Clinical Investigators
• Advertisements may state that subjects will be
  paid, but should not emphasize the payment or
  amount paid.
• FDA considers payment to research subjects to be
  a recruitment incentive, not a benefit of
  research.

24
RecruitmentGuidance on Advertising

• FDA Information Sheets Guidance for IRBs and
  Clinical Investigators
• any advertisement to recruit (research) subjects
  should be limited to the information the
  prospective subjects need to determine their
  eligibility and interest.
• Name and address of clinical investigator
• Condition under investigation and/or purpose
• Summary of criteria used to determine elegibility
• Brief list of benefits, if any
• Time commitment required of subject
• Location of research and name/telephone number of
  contact person

25
RecruitmentGuidance on Advertising

• When writing or reviewing a research subject
  recruitment advertisement, points to consider
• Could the language be coercive?
• Does the description of the study procedures
  accurately reflect the study design?
• Will the subjects undergo procedures or tests
  that carry risk or cause discomfort?
• Will the audience to whom the ad is directed
  understand the significance of the language used?
• Does the language comply with FDA guidance?

26
RecruitmentHow to plan your recruitment strategy

• Identify the target research population
• Develop a recruitment timeline with milestones
• Develop a profile of potential research subjects
• Verify sources of potential subjects
• Determine methods of approaching each source
• Identify recruitment advertising media
• Develop materials (IRB)
• Develop a questionnaire (source document)
• Develop plan on how you will process potential
  participants

27
RecruitmentHow to plan your recruitment strategy

• Develop plan on how you will obtain informed
  consent and screen potential research subjects
• Decide how you will evaluate performance metrics
  (established benchmarks) and develop corollary
  methods to accomplish your recruitment goals
• Document your recruitment strategy and share it
  with your sponsor
• Last but not least, make absolutely sure that
  your study related budget has money to support
  your efforts!