The changing landscape of product development and randomized trials.

Controversy exists about whether or not similar standards apply to the clinical evaluation of orthopaedic implants and pharmaceuticals. The long-lasting dispute is likely to be abandoned shortly, given that certain regulatory bodies in Europe now mandate proof of effectiveness by randomized controlled trials (RCTs) prior to market approval of innovative devices. This is a timely signal--it will help to strengthen both the credibility of orthopaedic researchers among all health-care disciplines and the role of manufacturers as creative minds and scientific partners. Yet, it must be accompanied by substantial changes in the current trial landscape. Given the level of perfection of available orthopaedic technology, superiority of a new product over an established standard will become a rare finding. Noninferiority or equivalence must be accepted as important trial results by investigators, sponsors, clinicians, and health authorities to enhance the spectrum of therapeutic options and help to individualize patient care. Specific problems are slow recruitment rates and long intervals from the protocol stage to publication of results. This may counteract the innovative potential of a novel product. Pragmatic trial designs, lean but complete documentation, limited but precise end points, the avoidance of competing trials, and the fostering of international collaboration are possible ways to streamline clinical trials of orthopaedic devices. Finally, RCTs should be conducted, conditional to the presumed level of innovation of a new implant, and supplemented by data from registries to fully determine the utility, value, and safety of the intervention.