Issues in the planning and conduct of non-randomised studies.

This paper discusses topics related to the planning and implementation of non-randomised clinical studies in orthopaedics. A well-conducted case-series is appropriate to demonstrate the safety of a surgical intervention. The case-series design involves the provision of a defined intervention to a group of patients with the ultimate objective of describing the final outcome, including such occurrences as complications. There is no alternative procedure serving as a control. The key aspects are to ensure enrolment of all eligible patients and to obtain a sufficiently large sample size to allow precise and valid estimation of complication risks. Targeted complications should be clearly defined and fully documented during a pre-defined follow-up period. Loss to follow-up should be minimised. Comparative studies are required to demonstrate treatment effectiveness. If a randomised controlled trial (RCT) is not feasible, an observational design such as a cohort or a case-control study should be considered. In observational designs, the treatment decision is made by the surgeons. In a case-control study, patients are selected based on their outcomes and their treatment or exposure status is recorded retrospectively. In a cohort study, groups of patients are selected based on their treatment and are followed for outcomes. There are numerous variations. Data can be collected prospectively or retrospectively; comparison groups may be concurrent or non-concurrent, or studied at different locations. The optimal design is tailored to clinical questions and research settings, while keeping in mind the respective methodological strengths and weaknesses of available options. The strength of the observational study is its proximity to daily clinical practice. The limitations are the possibility of numerous biases and confounding factors. Despite many challenges to the internal validity of non-randomised studies in orthopaedics surgery, it is possible to use such designs in order to provide reasonably valid answers to clinically important questions.