Efficacy assessed in follow-ups of clinical trials methodological conundrum.docVIP

Landewé Arthritis Research Therapy 2010,12:132 /content/12/4/132 EDITORIAL E? cacy assessed in follow-ups of clinical trials: methodological conundrum Robert BM Landewé* See related research by Rantalaiho et al., /content/12/3/R122 argument that ‘treat to target’ is the best way to exploit Abstract those bene? ts is convincing [1]. Increasingly, we see papers describing the long- term follow-up results of randomised clinical trials. Sometimes, like the article by Rantalaiho and colleagues in the previous issue of Arthritis Research Therapy, the follow-up extends to more than 10 years. It is not uncommon that authors of such articles describe their results as a comparison of the original treatment groups in the original randomised clinical trial. Methodologically, such a comparison is fallible for several reasons. In this editorial, two important sources of bias that may jeopardise the results of such follow- up studies are discussed: confounding by indication What concerns me most in Rantalaiho and colleagues’ interpretation – and admittedly in similar exercises in which I took part myself [2,3] – is the implicit assumption that two groups of patients formed a decade ago by a stochastic process that we call randomisation can be compared 11 years later under the same premise of prognostic similarity. Groups in randomised clinical trials (RCTs) may violate prognostic similarity even at baseline. Chance theory tells us that if we were to perform the procedure of randomisation 1,000 times, we may face a number of attempts with a number of imbalances, sometimes even and confounding by trial completion. in prognostically relevant variables. We usually ignore such baseline di? erences, assuming that imbalances may occur in either direction, and their combined net e? ect Long-term follow-ups of randomised clinical trials are a on the outcome of interest is probably neglig