Ethics Forum: The Ethical Pitfalls of Clinical Trials

I would not enroll in the pain trial described in the vignette above. If I were a patient with gout, I would not have enrolled in the febuxostat/allopurinol trials knowing I might receive allopurinol at a suboptimal dose. Accordingly, I would not encourage my patients to enroll in such trials.

The Bottom Line

Choosing an appropriate comparator in a clinical trial can be tricky.12 Ethical issues may arise when the comparator group does not receive what we know or believe to be the best available treatment. We should set a high bar for clinical trials, and that means that a treatment that is common but suboptimal may not be good enough. Indeed, it may even be unethical.

Dr. Shmerling is clinical chief of the division of rheumatology and program director of the BIDMC rheumatology fellowship at Beth Israel Deaconess Medical Center in Boston.

References

1. The Nuremberg Code. JAMA. 1996;276:1691.
2. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The Belmont Report. Washington, DC: US Government Printing Office; 1979.
3. Council for International Organizations of Medical Sciences. International Ethical Guidelines for Biomedical Research Involving Human Subjects. Geneva, Switzerland: CIOMS; 1993.
4. Strand V, Cohen S, Schiff M, et al. Treatment of active rheumatoid arthritis with leflunomide compared with placebo and methotrexate. Arch Intern Med. 1999;159:2542-2550.
5. Lipsky PE, van der Heijde DM, St Clair EW, et al. Infliximab and methotrexate in the treatment of rheumatoid arthritis. Anti-tumor necrosis factor trial in rheumatoid arthritis with concomitant therapy study group. N Engl J Med. 2000;343:1594-1602.
6. Becker MA, Schumacher HR Jr, Wortmann RL, et al. Febuxostat compared with allopurinol in patients with hyperuricemia and gout. N Engl J Med. 2005; 353:2450-2461.
7. Schumacher HR Jr, Becker MA, Wortmann RL, et al. Effects of febuxostat versus allopurinol and placebo in reducing serum urate in subjects with hyperuricemia and gout: A 28-week, phase III, randomized, double-blind, parallel-group trial. Arthritis Rheum. 2008, 59:1540-1548.
8. Ogryzlo MA, Urowitz MB, Weber HM, Houpt JB. Effects of allopurinol on gouty and non-gouty uric acid nephropathy. Ann Rheum Dis. 1966;25:673-680.
9. Perez-Ruiz F, Alonso-Ruiz A, Calabozo M, Herrero-Beites A, Garcia-Erauskin G, Ruiz-Lucea E. Efficacy of allopurinol and benzbromarone for the control of hyperuricaemia: A pathogenic approach to the treatment of primary chronic gout. Ann Rheum Dis. 1998;57:545-549.
10. US National Library of Medicine DailyMed: FDA information: Allopurinol tablet. Available at http://dailymed. nlm.nih.gov/dailymed/search.cfm?startswith=allopurinol. Accessed February 2012.
11. Emanuel EJ, Wendler D, Grady C. What Makes Clinical Research Ethical? JAMA. 2000;283:2701-2711.
12. MacKenzie CM, Paget SA. Ethics in Clinical Trials In: Hochberg MC, Silman AJ, Smolen JS, et al. eds. Rheumatoid Arthritis, 1st ed. Philadelphia, PA: Mosby Elsevier; 2009: 413-418.