# Presentation: 261431

## Ethical Issues in Subject Enrollment

- Joal Hill, JD, MPH
- Advocate Health Care
- Chicago, IL

## Objectives

- Consider changes in the research environment that affect subject enrollment
- Review **justice** as a foundational ethical principle in human subject research
- Recognize circumstances where research team may feel pressured to enroll subjects who do not meet study criteria

## The Research Environment

- 1991-98: pharmaceutical funding to academic medical centers decreased from 80% to 40%
- 1990-97: number of private physicians conducting research tripled
- During the year 2000: 4,360 new drugs developed in US, Europe, and Japan.
- This figure was expected to grow 12% each year for five years: 6,125 new drugs in 2003

## The Research Environment

- About 80% of all trials miss their enrollment deadlines (Centerwatch).
- Each day a drug is late to market costs about $1.5 million in lost revenue and patent protection.
- Increase in longitudinal studies

## Research Environment

- Increased incentives for all members of the research team (money, stock ownership)
- Subjects have more information, are more politically active

## Summary

- More naïve researchers/teams
- The need for subjects is growing faster than the pool of potential subjects is expanding
- “Time is money” in the industry
- Competition for subjects and sponsorship is greater
- Incentives are more lucrative
- Subjects are more likely to request participation in research

## Justice = fair distribution of burdens and benefits

- Group that bears the burdens should also receive benefits
- Benefits should be proportionate to burdens
- Vulnerabilities should not be exploited
- Unavoidable burdens should be minimized
- Harm should be fairly compensated

## Enrollment as an issue of justice

- Enrollment criteria should be fairly applied so that:
- Subjects who truly qualify will be included
- Potential for individual *and* societal benefit will be maximized
- Illness itself is coercive and makes potential subjects *and* researchers vulnerable to the emotional context (especially “last hope” and “best hope” studies)

## Why enroll a subject who does not meet eligibility criteria?(Vanderpool and Weiss)

- “Last hope” trial
- “Best hope” trial
- Honest mistake, e.g. misinterpretation of eligibility criteria
- Purposeful breach of criteria for some gain (professional, financial)
- Also: Subject requests/demands enrollment and agrees to assume the risk

## Can inclusion be justified?

- Duty to promote common good
- Respect for persons (autonomy)
- Golden Rule Principle (“I hope someone would make an exception for me.”)

## Inclusion cannot be justified

- Human subject research cannot benefit society without careful controls (exception for one does *not* promote common good)
- The aggregate effect of individual actions must be considered – increased exceptions increase the risk of harm, _*and*_ may exclude truly eligible subjects once enrollment numbers are reached
- Golden Rule Principle only applies to situations that are *morally * unique.  Each subject’s suffering is unique, but not morally unique.

## What is the harm?

- Blurs distinction between goals of research and clinical care
- Contaminates study data
- May result in physical harm to subject
- Erodes personal and public trust
- “The moral havoc resulting...far exceeds the moral tradeoffs.”

## Easing the Ethical Tension(Vanderpool & Weiss)

- Regulate media reports of promising new data
- Develop policies for treating ineligible patients outside research protocols
- Explore policies for identifying and censuring/fining, or otherwise penalizing researchers.

## Confusion about Research vs. Established Therapy

- Therapeutic misconception more likely when subject already has relationship with research team for clinical care
- Obligation to do “something” versus “nothing” or “palliative care only” reflects lack of understanding about the goals and limits of medicine

## Confusion about Research vs. Established Therapy

- Wanting to offer the “best” or “most recent” therapy blurs the goals of research versus clinical care

## From an IRB Perspective

- Consent (ongoing or continuing)
- Coercion (of medium and message) – may be unintentional but still damaging
- Confidentiality (and privacy)
- Completeness (accurate and truthful, not deceptive)