Comparative information on new medicines : availability, quality and usage

When a new medicine is marketed, it is important to know how it compares with existing medicines for the same indication. Healthcare professionals and regulators all require this comparative information in order to make decisions on prescribing and reimbursement. Evaluating differences between medicines can best be studied in randomized controlled trials with an existing medicine as the active control group (RaCT). The lack of outcomes of comparative research upon the introduction of a new medicine is regarded as an important problem. However, statistics on the nature and extent of this problem are scarce. The aim of this thesis is to shed light upon this problem by carrying out an evaluation of the availability, quality and the use of the comparative information on new medicines at the moment of market entry. Methods For the studies in the thesis we used the data from the pivotal trials of medicines with a new active substance that were authorized through a Centralised Procedure by the European Commission between 1999 and 2005. Information was extracted from the European Public Assessment Reports (EPARs). Information on publications was obtained from the MEDLINE and EMBASE databases. Results We identified 122 new medicines, of which 58 (48%) had been studied in comparison with an existing medicine. For 33 (27 %) medicines, the results were publicly available as a peer-reviewed publication at the moment of market entry. After two years 78% and after three years 83% of the RaCTs had been published. A new mechanism of action of a new medicine was shown to be a limiting factor in providing comparative information. Of the new medicines, 13 (10%) demonstrated a statistically significant difference in efficacy in comparison with an existing medicine. In a case-study on etanercept, a new medicine without premarketing RaCT, we found that the post-approval trials were unsuitable to answer the demands from clinical practice for more comparative information. Further we found that 47 (81%) new medicines were compared with the recommended standard treatment in at least one trial. We experienced problems interpreting the public data of noninferiority and equivalence trials, as these trials provide insufficient additional information on the comparator in public sources of information on these trials. In an evaluation on decisions on comparative efficacy, for 50 (72%) of the new medicines studied, sufficient premarketing data were available for a clear opinion. However, for only a few (12%) the body of evidence could be ranked at the highest level and for about 40% at the lowest level: the expert opinion. Conclusions The lack of comparative data on one out of two new medicines and the problem of accessibility to the full data of premarketing RaCTs at market entry, represents an obstacle to optimal decision-making on prescribing and reimbursement at the moment when the need is greatest. Though the goal of developing new medicines should be to improve treatment, this is not always apparent from the objectives and outcomes of premarketing research. Optimal pharmacotherapy would benefit from more comparative research in the development of new medicines