Subgroup Analyses: When Should We Believe Them?

Abstract

You are an orthopaedic oncologist who has recently excised a high-grade soft-tissue sarcoma from the thigh of a fifty-year-old woman. This patient does not have metastatic disease, has had preoperative radiation, and is now in your clinic for her second postoperative visit. After some wound-healing issues, her wound is now healed and she would like to know if her chance of long-term survival would increase if she underwent adjuvant chemotherapy. Your sarcoma multidisciplinary team generally does not offer chemotherapy to patients with localized disease. However, you decide to consult the literature. You find a meta-analysis by the Sarcoma Meta-analysis Collaboration (SMAC) that was published in The Lancet in 1997 and by the Cochrane Collaboration in 20001. The meta-analysis includes data from fourteen trials involving 1568 patients with localized soft-tissue sarcoma who were randomized to chemotherapy or to no chemotherapy. The article concludes that “there is evidence that doxorubicin-based chemotherapy after initial treatment reduces recurrence, either at the original site or elsewhere in the body…[and] seems to increase the length of time patients live, but this is less certain.” Based on nine subgroup analyses of treatment effect, “greater benefit was seen in men and those whose tumor originated in a limb.” Given the conclusion of the meta-analysis, would you choose not to offer chemotherapy because of the fact that your patient is female? Information obtained from randomized controlled trials is considered the best available evidence for determining a therapeutic treatment effect. However, randomized trials assess a representative sample of patient populations. In order to provide data on individual subsets of patients, subgroup analyses are often done2-4. Information from subgroups is potentially helpful for making treatment decisions for individual patients. In fact, a large percentage of clinical trials include subgroup analyses with the goal of meeting …