1. ETHICAL ASPECTS of PLACEBO SURGERY AAOS ETHICS COMMITTEE Matthew J. Matava, MD 1

2. Objectives Understand the definition of placebo (“sham”) surgery and its accepted indications Identify the major differences between medical placebos and sham surgical procedures Identify the ethical implications of sham surgery and the proposed benefits it may provide in orthopedic research Understand the ethical criticisms against sham surgical procedures 2

3. Case Dr. Janus is an orthopaedic surgeon specializing in arthroscopic surgery. Lately, he has treated many older patients with osteoarthritis in their knees. Patients continue to request this procedure hoping to improve their mobility. J upiterimages/PhotoObjects/Thinkstock 3

4. However, in reviewing the current literature, Dr. Janus learns that the type of arthroscopic knee surgery he has been performing routinely (arthroscopic lavage and debridement) has been shown to provide no benefit Stockbyte/Thinkstock over placebo. In fact, a strong placebo effect has been suggested. 4

5. Mr. Jimson is a 70-year-old retiree living on his limited pension. He suffers from advanced osteoarthritis in his knees and would do anything to be able to walk more easily on his own. He enters iStockphoto/Thinkstock Dr. Janus' office one day requesting arthroscopic surgery for the osteoarthritis in his knees. 5

6. He says to Dr. Janus, “My best friend had this surgery last month, and he's already getting around the golf course great! He says this surgery was the best thing he ever did for himself. I sure would love to be able to keep up with him now. iStockphoto/Thinkstock What do you say doc, can you do this surgery for me?” 6

7. What are the practical issues? What are the financial issues? What are the ethical issues? 7

8. General Issues Pros Patients generally do well after arthroscopic lavage. The patient is requesting the surgery. The complication rate for knee arthroscopy is low. 8

9. General Issues Cons The procedure can be expensive for some patients. All surgical procedures have potential complications. Arthroscopic lavage for osteoarthritis is possibly no better than a ‘sham’ surgery. 9

10. Topics to Consider Dr. Janus has noticed that his patients do very well, at least temporarily, following knee arthroscopy for osteoarthritis. He always keeps up with current medical research. Based on the available literature, Dr. Janus cannot distinguish the benefit his patients receive from this operation from placebo. The total financial implications of knee arthroscopy for osteoarthritis approaches $3 billion in the U.S. Dr. Janus prides himself on practicing cost- effective medicine. What would you do? 10

11. What would you do? 11

12. Orthopaedic Considerations Approximately 650,000 arthroscopic procedures for treating osteoarthritis of the knee are performed annually in the U.S. at a cost of approximately $4500 each. Most clinical series have shown success rates following arthroscopic debridement that vary from 50%-75%. 12

13. Mosely et al. 1 investigated the benefit of arthroscopic surgery in 180 older adults, with a mean age of 75 years, suffering from osteoarthritis of the knee. Patients were randomized to three study arms:  arthroscopic debridement  arthroscopic lavage  sham operation consisting of three 1-cm portal incisions. The primary outcome measure was knee pain two years after surgery. The Mosely study found no significant difference between treatment arms of the study, thus concluding that routine arthroscopic lavage and/or debridement was no better than the sham procedure. 13

14. Do the results of the Mosely study change your opinion of the benefit of arthroscopic surgery of the osteoarthritic knee? What other information would you need to know before recommending knee arthroscopy for a patient with osteoarthritis of the knee? 14

15. How do you define equipoise? What is the role of equipoise in research involving placebo (“sham”) surgery? 15

16. How do you define placebo? Under what circumstances is it allowable to use a placebo in a study? 16

17. Under what circumstances is it acceptable to use a placebo (“sham surgery”) in a clinical trial? Was it acceptable to use “sham surgery” in the Moseley osteoarthritis trial? 17

18. Case Study - Conclusion Dr. Janus performed an arthroscopic debridement on Mr. Jimson’s knee after a thorough discussion of the risks and potential benefits of the procedure including the need for further surgery. There were no complications to the procedure. At the 3 month postoperative visit, Mr. Janus stated that he felt considerably better with less knee pain and swelling. He told Dr. Janus that he was glad he underwent the surgery. At 1 year after surgery, Mr. Janus began experiencing recurrent knee pain but no locking or catching symptoms. 18

19. Now, what would you do? 19

20. Summary A careful history and examination with appropriate radiographic studies should always be performed. The physician should consider all options of non-invasive and invasive care once a diagnosis is made. The alternatives should be reviewed and the risks and benefits given careful consideration. The treatment must first do no harm and be of benefit to the patient from an ethical perspective. 20

21. The concerns and goals of the patient need to be explored relative to the issues presented by the available literature. Informed consent is mandatory. The experience of the physician should also be explored and ample time devoted to the perspective of the patient.  This conversation should be documented as part of the informed consent process. The placebo effect of any treatment should be considered as well. Despite the fact that one can argue that the placebo effect places the patient at risk for questionable gains, one can also argue that the benefits often outweigh the risks. 21

22. The ethical issues of informed consent, beneficence and non-maleficence need careful consideration in all clinical decisions. Shared decision making, patient-centered health care principles, and cost-effective medicine should be utilized to tailor the care to the individual patient. 22

23. References 1.Moseley J, O’Malley K, Petersen N, et al: A controlled trial of arthroscopic surgery for osteoarthritis of the knee. N Engl J Med 2347:81- 8, 2002. 2.London A, Kadane J: Placebos That Harm: Sham Surgery Controls in Clinical Trials. Stat Methods Med Res, 11: 413-427, 2002. 3.McDonald P, Kulkarni A, Farrokhyar F, Bhandari M: Ethical Issues in Surgical Research. Can J Surg 53: 133-136, 2010. 4.Jones J, McCullough L, Richman B: The Ethics of Sham Surgery in Research. J Vasc Surg 37: 482- 483, 2003. 23

24. 5.Boyle K, Batzer F: Is a Placebo-controlled Surgical Trial an Oxymoron? Journal of Minimally Invasive Gynecology 14: 278-283, 2007. 6.Angelos P: Sham Surgery in Research: A Surgeon's View. The American Journal of Bioethics 3: 65-66, 2003. 7.Tenery R, Rakatansky H, Riddick F, et al: Surgical “Placebo” Controls. Ann Surg 235: 303–307, 2002. 8.Macklin R: The ethical problems with sham surgery in clinical research. N Engl J Med 341:992–996, 1999. 24

25. Miller F: Sham Surgery: An Ethical Analysis. The American Journal of Bioethics 3: 41-48, 2003. Stock G: If the Goal Is Relief, What's Wrong with a Placebo? The American Journal of Bioethics 3: 53-54, 2003. American Academy of Orthopaedic Surgeons: Code of Ethics and Professionalism for Orthopaedic Surgeons, I.A, II.A, II.B. Adopted October 1988, revised 2011. http://www.aaos.org/about/papers/ethics/code.asp Council on Ethical and Judicial Affairs: Code of Medical Ethics, Opinion 2.076. Chicago, IL, American Medical Association, ed 2012-2013. 25