This is a lecture on ethical issues related to clinical trials. It is for Module 4 of an online Medical Ethics course I am teaching at BGSU.

1. The Ethics of Clinical Trials Medical Ethics Online Summer 2011 Eli Weber-Instructor

2. Lecture Goals Explain the structure and organization of clinical trials Highlight the ethical dilemma that clinical trials create for physicians Outline the “standard” respond to this dilemma Consider some further ethical issues associated with clinical trials

3. What is a Clinical Trial? A clinical trial is a research study designed to test the effectiveness and side effects of a treatment for human subjects. 4 Phases -Phase 1-tests for toxicity only -Phase 2-tests efficacy, further evaluates toxicity -Phase 3-confirmation of efficacy in larger group -Phase 4-fine tuning

4. Why Clinical Trials? Limits of animal experimentation More reliable than other sources of evidence -Isolates relevant variable Control groups Randomization Blindness

5. Ethical Issues with Clinical Trials Embarrassing History Treats patients in the control group as a means to an end. -Conflict between physicians’ duty of beneficence and randomization If physicians have a duty to recommend the treatment that they believe to be best, suggesting a clinical trial for a patient is rarely consist with this duty, because there is nearly always a better option for the patient.

6. Ethical Issues with Clinical Trials -Placebos vs. Active-control studies A placebo study is never acceptable when there is an available treatment that is known to be effective. Active-control studies involve comparing promising new treatments against treatments regarded as inadequate. Standard worries with informed consent -ability to understand relevant information -vulnerable populations -coercion

7. Typical Reply to Ethical Objections There is no ethical conflict between a physicians’ duty of beneficence and offering the patient the option of participating in a clinical trial, provided certain conditions are met: Genuine clinical equipoise exists Physician explains that their recommendation is based on evidence that isn’t the “gold standard.” -This is a component of informed consent -Marquis: physicians have a duty to offer clinical trials in these cases *Also addresses concerns about active-control studies.

8. Typical Replies to Ethical Objections If patients give informed consent, it is acceptable to use them as a means. In general, these issues are dealt with by appeals to informed consent and restrictions on when clinical trials are acceptable. The medical community defends a moderate view about the ethics of clinical trials.

9. Further Issues with Clinical Trials How do we assess clinical equipoise? How much equipoise is enough? -PLX4032 Clinical trial Balancing the need for information about long-term effectiveness against the fact of immediate need. -Is it ethical to continue a study in the face of compelling evidence of efficacy, for the sake of assessing long-term effects?

10. Further Issues with Clinical Trials Should pharmaceutical companies be allowed to hold a promising new drug off the market for the sake of obtaining further evidence of its efficacy? Can physicians fulfill their alleged duty to offer clinical trials without inadvertently coercing participation?

11. The Bottom Line Clinical trials appear to be a necessary component of medical research. The ethical issues associated with clinical trials are numerous, and often involve patient autonomy and well-being juxtaposed with the duties of physicians and benefits to future generations (in addition to the standard worries about informed consent). It’s not clear that informed consent is the “magic” solution to ethical issues related to clinical trials.