# Presentation: 416724

## Clinical Care vs. Clinical Research: The Therapeutic Misconception

***Howard Brody, MD, PhD***
***Center for Ethics & Humanities***
***Family Practice***
***Michigan State University, East Lansing***

## A Personal Anecdote

## A Personal Anecdote

**DOC**

**INVESTI-**
**GATOR**

## Clinical Research and Clinical Therapy: Two Stances

- Similarity Position: Ethics of research should be based on the ethics of therapeutic medicine
- Difference Position: The two activities are fundamentally different and require different ethical approaches
- Miller & Brody, *Hastings Cen Rep* 33(3):19, 2003

## R. Levine, 1979

- An expert physician-investigator in 1970:
- “Every time a physician administers a drug to a patient, he is in a sense performing an experiment.”
*Hastings Cen Rep* 9(3):21, 1979

## National Commission, 1978

- One may perform ***experimentation*** in either the research or the therapeutic setting
- But ***experiment*** does not equal ***research***
- The worlds of ***research*** and ***therapy*** are in fact quite distinct and separate
- Levine, *Hastings Cen Rep* 9(3):21, 1979

## World of Therapeutic Medicine

- Goal: provide benefit to the individual patient
- Ethical principles:
- Therapeutic beneficence
- Therapeutic nonmaleficence
- Any new knowledge generated is incidental to overriding goal of activity

## World of Clinical Research

- Goal: New knowledge that can help future patients (generalizable)
- Ethical principles
- Autonomy
- Nonmaleficence
***Utilitarian*** balancing of risks and benefits
- Therapeutic benefit ***to individual*** is secondary to overriding goal

## Example: Depression Treatment

- 200 patients with depression
- Choose an antidepressant for each based on individual characteristics
- Alter doses according to individual responses
- Use concomitant meds (or not) based on symptoms
- After 12 weeks: wide variation

## Example: Depression Trial

- Randomize subjects to antidepressant A or B
- Probably use standardized doses
- Alter doses (if at all) according to rigid schedule
- Avoid any concomitant medications
- Goal: Maximum uniformity at 12 weeks

## Importance of National Commission (Belmont Report, 1978)

- Laid groundwork for entire apparatus of institutional review of research
- Logic of review by an outside body is predicated on the distinction between research and therapy (as opposed to trusting the “personal physician’s” good intentions and professionalism)

## Implications for Informed Consent

- Informed consent a major ethical requirement for research
- Informed consent should start with a clear orientation to ***what sort of setting*** one is in
- The patient-subject who thinks he is getting individualized therapy when in fact he is being treated according to a research protocol cannot give informed consent

## Implications for Informed Consent-II

- Blurring the distinction between research and therapy (e.g., similarity position) risks undermining the entire process of informed consent

## Therapeutic Misconception

- Research subject’s belief that enrolling in research trial will (with certainty) provide direct therapeutic benefit, despite what appears to be an adequate informed consent process
- 40-80% of subjects showed basic misunderstandings of research trial design
- Appelbaum et al., *Hast Cen Rep* 17(2):20, 1987

## Have Things Improved?

- “Our current research suggests that as many as 70% of subjects in a wide variety of clinical research studies may suffer from a therapeutic misconception.”
- Appelbaum, *AJOB* 2(2):22, 2002

## Where Does the Misconception Originate?

- Assumption: subject’s psychological need for an effective cure for her disease, despite honest effort at informed consent
***If ***investigator confuses clinical research with clinical therapy, stage is set for subject to get erroneous impression as to basic nature of the setting and activity

## The Problem of Clinical Equipoise (CE)

- Similarity Position yields “RCT dilemma”
- How can randomization be justified within a therapeutic ethic?
- CE is an attempt to answer the RCT dilemma
- RCT is ethical ***only if*** the medical community is genuinely uncertain which of two treatment arms is superior

## Clinical Equipoise-II

- CE claims the virtue of preserving the basic duty of therapeutic beneficence
- No subject randomized to a treatment known to be inferior
- Therefore, CE exemplifies and logically implies the Similarity Position
- The Difference Position deals with the “RCT dilemma” by rejecting it as false

## Clinical Equipoise-III

- “The Declaration of Geneva ...binds the physician with the words, ‘The health of my patient will be my first consideration.’”
- “The primary purpose of medical research...is to improve prophylactic, diagnostic and therapeutic procedures and the understanding of the aetiology and pathogenesis of disease.”
- Declaration of Helsinki, WMA, 2000

## Clinical Equipoise-IV

- CE promotes the therapeutic misconception at ***all levels ***(subject, investigator, IRB)
- CE promotes the larger misconception that ***both*** physicians and research studies are nothing but retail pharmacies
- Focuses solely on what treatment is received, not how the setting is designed or how treatment decisions are made

## Conclusions

- Solid understanding of research ethics requires the clear distinction between research and therapeutic contexts (Difference Position)
- Therapeutic misconception is a major practical problem in research

## Conclusions--II

- Blurring the research/therapy distinction  (Similarity Position, CE) seems highly likely to worsen the therapeutic misconception problem
- Many statements of research ethics today are incoherent and don’t know it (e.g., Declaration of Helsinki)