Interpreting surgical trials with subjective outcomes: avoiding UnSPORTsmanlike conduct.

IN THIS ISSUE OF JAMA, 2 ARTICLES 1,2 REPORT RESULTS OF the Spine Patient Outcomes Research Trial (SPORT). One study is a multicenter trial of patients with persistent disk-related pain and neurologic symptoms randomized to undergo diskectomy or receive usual care (most often, patient education, anti-inflammatory medication, and physical therapy, alone or in combination). Because the investigators expected high rates of refusal of randomization based on the differential risk of these 2 treatment strategies, they developed a parallel observational study of patients who qualified for the randomized trial but refused randomization. Patients in both the randomized trial and the observational cohort study were similar in almost all characteristics and were followed up in a similar fashion for 2 years. The SPORT randomized trial had such a high proportion of patients who crossed over between treatment strategies (45%-60%) and such a significant degree of missing data (24%-27%) that an intention-to-treat analysis was not informative about the comparative efficacy of the strategies. The study showed that patients randomized to either operation or usual care improved considerably over the 2 years of the study and that patients who had an operation were more likely to have been severely affected by their disk pain than those who opted for usual care. Although it is tempting to consider “as-treated” analyses when looking for the effect of an intervention, such analyses are significantly confounded and should not be used to compare different strategies. For a different set of reasons, it is equally problematic to use the second, observational cohort study to understand the role of surgical intervention for discogenic pain. When evaluating subjective outcomes such as pain, satisfaction, and function after health care interventions, it is critical to distinguish the effect of the intervention from the effect of the patient’s expectation of the intervention. The impact of expectation on subjective outcome is commonly described as the placebo effect. The only way to distinguish the effect of a patient’s positive expectations of the operation from the intervention itself is to blind patients to the treatment they receive and then randomize them to receive the intervention of interest or to receive an ineffective, sham intervention (placebo). While this technique is well accepted in studies of medications using inactive pills (placebos), simulated acupuncture, and nontherapeutic conversation in place of therapeutic psychiatric interventions, it has only occasionally been applied to surgical trials. This is unfortunate because the use of sham controls has been critical in understanding just how much patient expectation influences outcome after an operation. Given the proliferation of operative procedures for the treatment of subjective complaints like back pain, the need for shamcontrolled trials has never been greater. A dramatic demonstration of the power of suggestion in surgical outcomes can be found in one of the first shamcontrolled surgical studies, performed in 1959. After multiple observational studies suggesting that ligation of the internal mammary artery was helpful in patients with coronary disease, Cobb et al randomized patients to operative arterial ligation or a sham procedure. Both groups improved after the intervention, but there were similar, if not greater, improvements in subjective measures such as exercise tolerance and nitroglycerin use in the sham surgical group. More recently, after multiple case series demonstrated that patients with osteoarthritis of the knee improve after arthroscopic surgery, Moseley et al demonstrated just how much of that effect is related to the hopes, expectations, and beliefs of the patient. The investigators randomized 180 patients to undergo arthroscopy with debridement, arthroscopy with lavage, or sham arthroscopy. The power of expectation was so strong that patients could not determine if they were assigned to the treatment or sham groups— and all groups improved. At 2 years after randomization, all patients reported comparable pain scores and functional scores. There have been several other arenas of invasive health care intervention in which observational trials have shown procedural success but sham-controlled trials demonstrate how much of that success is due to the placebo effect. Another sham-controlled study in patients with knee osteoarthritis demonstrated that patients benefit equally from irrigation of the joint and sham irrigation. Researchers found similar improvements in quality of life after direct brain injections of embryonic neurons or placebo in patients with