Ethical Factors in the Recruitment and Retention of Research

Report
Ethical Factors in the
Recruitment and Retention of
Research Participants
Frederick W. Luthardt, MA, MA
Research Participant Advocate, ICTR Bayview CRU
Compliance Specialist, JHM OHSR
Introduction
…or, preaching to the choir
• The real-world question: “Isn’t following the rules
enough?
• Ethic principles are important to the conduct of human
subjects research, and applicable along the entire arc of
a study.
• No guarantee: Ethical integrity does not lead to
success…
• Guarantee: Ethical failures can
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compromise the integrity of the study
harm the rights, safety, and welfare of the participant
challenge the usefulness/quality of the study’s data
cause insomnia, locusts, plague, etc.
To do list…
• Discuss current concerns with Recruitment and
Retention in Human Subjects Research
• Survey challenges faced by researchers
• Look at the “back-drop” of Federal Regulations
and Institutional Requirements
• Present a brief review the history of research
ethics, culminating with the Belmont Report
• Summarize basic ethical principles
• Examine some ways ethics can be applied to
Recruitment and Retention
Definitions
• Recruitment – getting the attention of and
attracting potential research participants, i.e.,
“casting a net.”
– Uses the IRB’s application distinction, recruitment is a distinct
process from consent (i.e., “enrollment”).
– In “the real world,” the process in on a wide continuum:
• IRB approved newspaper ads, flyers, radio/TV spots, etc.
• Sending IRB approved “Information Packets” after first
contact (e.g., study FAQs, the IRB approved consent, etc.)
• The “pre-enrollment” conversation (e.g., on the phone, faceto-face) has its own dynamic, with ethical implications
– may include subtle (subjective) or direct (objective) “screening”
– the actual private conversation can’t be feasibly monitored
Definitions continued…
• Retention: Research participants remaining in
the study for its duration, to provide evaluable
data and attain study objectives.
– Also referred to as “attrition” (participants leaving the
study prematurely and/or being “lost to follow up”)
• Can be influenced by the study itself or staff
• Participants themselves can make or break
retention.
The Situation
• There are two basic recruitment scenarios:
– Scenario #1: recruitment happens the day of consent
(e.g., potential participants are approached and
enrolled in a clinical setting, often without recruitment
materials)
– Scenario #2: the recruitment process precipitates
from a person responding to a study’s newspaper ad
or posted flyer, and may involve several encounters
prior to consent
• The focus of this presentation will be on #2, i.e.,
the “pre-consent” phase, followed by the issues
related to retention
General Recruitment Issues
• The recruitment of study volunteers is a top
concern for researchers:
• Many studies do not meet their recruitment goals
• There is a disproportionate lack of women and minority
representation in clinical trials.
• IRB monitoring has found that many JHM studies have
difficulty with recruitment/enrollment, at some point.
• A major confounding affect to recruitment is the
public’s understanding of clinical research:
• potential volunteers may be reluctant to join a study based on
many factors: education, socio-economic factors, fear, etc.
General Retention Issues
• Retention (or “attrition”) may not be seen as
rising to the level of recruitment (what I call the “Table 1
effect”)
• However, retention is critical to the success of a
trial because:
– Keeping an evaluable proportion of the sample-size is
necessary for statistical significance,
– Continued or new funding may suffer
– Longer therapeutics development, etc.
Specific Recruitment Challenges
• Investigator side:
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Unrealistic recruitment goals
Inadequate recruitment strategies
Inclusion/exclusion criteria too tight
Materials that are inaccurate or “oversell” the study
• The Participant side:
– Study’s relevance
– Benefits (or harms)
– History of research abuses
– Respect (the “guinea pig” effect)
Specific Retention Challenges
• Investigator side:
– Study design requires high/impractical subject
compliance
– Expectations too high
• The participant side:
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Study demands are too high
Lack of immediate or perceived benefit
Take the money and run
Interpersonal issues
Disconnect between the consent and the study’s
procedures. “Can’t spell ‘consent’ without ‘con.’”
Federal Regulations Regarding Recruitment
• “The [Informed Consent, Cf. 21 CFR 50.25] process may
include recruitment materials, written materials, question
and answer sessions, and measurements of subject
understanding (i.e., the process of informed consent may
involve more than just the informed consent document).
http://www.fda.gov/downloads/AboutFDA/CentersOffices/DER/ManualofPoliciesProcedures/UCM
02024.pdf
• “HHS regulations at 45 CFR 46.109(b) require that IRBs
ensure that information given to subjects [e.g.,
recruitment materials] as part of informed consent meets
the requirements specified in the regulations at 45 CFR
46.116. http://www.hhs.gov/ohrp/policy/clinicaltrials.html
Federal Regulations Regarding
Participant Retention
• Nothing specified in the CFR
• However, enrolled subjects are free to
withdraw at any time (in keeping with
informed consent regulations)
• Subjects may be withdrawn for safety
reasons or other investigator determined
grounds
• Retention success or failure is determined
by the Investigator
Institutional (JHM)Requirements
Regarding Recruitment
• JHM IRB requires the following items be displayed on
recruitment materials:
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The name of the principal investigator;
The contact information to learn more about the study;
The condition under study and/or the purpose of the research;
A specific reference to “research study” in the text; and
The JHM IRB protocol number.
http://www.hopkinsmedicine.org/institutional_review_board/guidelines_policies/g
uidelines/study_subject_recruitment.html
• JHM IRB complies with the FDA/DHHS’s specified
recruitment materials elements
http://www.fda.gov/RegulatoryInformation/Guidances/ucm126428.htm
Institutional (JHM)Requirements
Regarding Retention
• IRB requires that Principal Investigators
account for the retention of study
participants:
– At Continuing Review, participants who left
the study early require an explanation
– Participants who leave a study secondary to
dissatisfaction or complaint, a serious event,
etc., require reporting to the IRB.
– Any retention problems may invoke further
inquiry from the IRB
Human Subjects Research History
• Ethical
Code
• Ethical
Principle(s)
• Ethical
Practice(s)
• Nuremburg Code
(1947)
• Autonomy; nonmaleficence
• Informed Consent,
without coercion
• Declaration of
Helsinki (WHO)
(1964)
• Belmont Report
(US) (1979,
1981)
• Autonomy of all
subjects, including
children
• Respect for persons
Beneficence
Justice
• Informed Consent;
proxy consent
FDA: 21 CFR 50, 56
DHHS: 45 CFR 46
• Informed consent
Benefits/risks
Fair enrollment and
distribution of
benefit(s)
The Belmont Report in Detail
• Has 3 main ethical principles focusing largely on
informed consent and the conduct of human subjects
research
– Respect for persons
• Subjects are autonomous and are free to join/withdraw
• Respect necessitates informed consent
– Beneficence
• Benefit (direct or indirect), with minimization of harm
– Justice
• The study should be fair and equitable in its overall conduct, including subject
selection and the distribution of risks/benefits.
The “Philosophy” behind the
Belmont Report
• Where ethics and regulations come together
• The Principles are considered “positive
duties”
– i.e., the Principles serve as guides for “what to do,” not
“what not to do.”
– “Prima facie” – compelling “on first face.”
– Also involves, as ethicists say, “Ethical Comportment” i.e.,
intent
• Ethical Principles are the groundwork for
morals and rules (i.e., “pre-regulatory”)
The Application of the Ethical Principles
to the Subject Recruitment Process
• The ethically sound recruitment materials and dialog
ought to include the principles below as guides:
– Respect for Persons:
• Accurate information to assure the potential participant can make an
informed, and voluntary decision to enroll and withdraw, without coercion or
inappropriate inducement
• Accurate and full disclosure of anticipated benefits (if any) and a disclosure
of the possible risks of the study
– Beneficence:
• The recruitment process should ultimately describe all the steps to maximize
the study’s benefit (if any) and minimize or avoid undue risk(s).
– Justice:
• The study should be seen by the participant as fair in that it’s open to all or
those in the cohort who would stand to enjoy the possible benefits of the
study. That the risks and benefits are interpreted by the participant as
equitably distributed.
The Application of Ethical
Principles to Subject Retention
• Respect for Persons necessitates:
– Continuous communication, where possible
– The study remains relevant
• Beneficence (non-maleficence) necessitates:
– Attention to the participant’s “well-being.”
– Attention to and management of adverse events
• Justice necessitates:
– That the participant has confidence and a sense of ownership in
the study and its outcome.
• The Ethical Principles do not “turn off” at the
signing of the informed consent
Additional Moral Implications That
Emerge from the Ethical Principles
• Relevant to both Recruitment and
Retention:
– Understandable language
– Sensitivity to the cohort
– Respect for confidentiality
– Reasonable compensation
– The participant’s “take-away” should be that
he/she is a valued stake-holder, and not a
“guinea pig.”
The Future of Research Participant
Recruitment…today
• Social Networking, peer to peer
– Facebook, MySpace
– (Privacy, confidentiality, information security, as related to identity as a
constituent of “personhood”?)
• Web-based recruitment
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Clinicaltrials.gov
Clinical Trial specific websites
Disease websites, support group blogs, etc.
(Accuracy of study benefits/risks, and results?)
• CROs
– PPD, Parexel, Covance, etc.
– (Bias toward the sponsor’s interests over the human participant?)
Take Home Points
• The Ethical principles are well-characterized in
the regulations and represent the best-practice in
the informed consent process
• These principles are also useful for the planning
and conduct of research participant recruitment
• These principles, as extended beyond the
consent process, may enhance participant
retention
• Overall, the research participant’s well-being is
the primary aim and purpose through all stages of
the investigation.
Conclusion
• Attention to the regulations and ethical principles, and
the knowledge of them is crucial.
– “tools and materials”
• Intention to apply the ethical precepts, for their own
sake as “the right thing to do.”
– “applying artistry with meaning”
• Ethical excellence in research combines both, in that
the “spirit and letter” of the Research Principles are
understood and implemented with the “moral will” to do
so.
– “the product is well-done”

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