In comparative superiority trials, the test drug is typically compared with a drug that is the standard of care or is the class market leader. The goal is to demonstrate superiority in efficacy, cost-effectiveness, patient satisfaction, quality of life, or another parameter that may be helpful in increasing market share. The aim is to publish the trial (preferably in a peer-reviewed journal) and use the data in a promotional campaign. Although historically such studies were often of poor design (e.g. inadequate sample size; inappropriate end-points) to obtain a superiority claim for use in promotional pieces, the FDA now requires two adequate and well-controlled clinical trials or one study large enough to detect clinically useful differences. These studies must have well-defined end-points that are relevant for both products and include a range of doses for each product to ensure an optimal response. Double-blind and, if necessary, double-dummy studies are generally favored over open-label trials. A placebo group is often added to minimize an active control bias (Spilker 1991).
One of the difficulties in conducting doubleblind comparative trials is acquiring suitable supplies of the comparison drug. The sponsor can request supplies from the competing sponsor or purchase the product on the open market and modify it (e.g. encapsulation; reformulation) or, via new packaging technologies, mask the identity of the product. These options increase the time and costs associated with the trial. Modifying the product requires the development of a pharmaceutical process and evidence of bioequivalence. This may be particularly difficult for a product with a unique dosage form (e.g. wafer or patch). There is also a risk that the competing sponsor will challenge the study results, citing formulation differences that may affect product efficacy.
Although obtaining clinical supplies from the competing sponsor is scientifically the best option, requests for such supplies may not be handled quickly or may be denied altogether. A study synopsis is usually required by the competing sponsor, so that the design and hypotheses can be evaluated for scientific rigor. The synopsis also alerts the competing sponsor to the ultimate aims of the study, giving their marketing group time to respond to potentially damaging data. As the marketplace becomes increasingly competitive, companies are less willing to provide supplies for comparative studies, so that alternatives should always be explored.
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