What is already known about this subject: Randomized active control trials are used by health care professionals and reimbursement authorities for the assessment of the added value of a new medicine. Failing to publish the results of clinical trials limits making an evidence based assessment and conducting systematic reviews.
What this study adds: About one-third of the comparative trials used in the authorization process are published at the moment of market authorization and about four out of five within 2 or 3 years. Most of the rest remain unpublished. Unpublished trials contain information regarding a different therapeutic use or a different comparator of the same medicine and, in some cases, have influenced the risk : benefit assessment of the registration authorities. A standardized public registration of results of the main premarketing trials is advocated to fill the publication gap.
Aims: To determine the time-lag between the EU authorization of new medicines and the publications of the main randomized active control trials (RaCTs) used in the authorization process and to compare unpublished with published RaCTs of the same medicine.
Methods: All RaCTs for new medicines with a new active substance, authorized between 1999 and 2003, were extracted from the European Public Assessment Reports (EPAR). Information about the publication status of RaCTs was obtained from the MEDLINE and EMBASE databases.
Results: We identified 116 RaCTs for 42 new medicines; 28% of the RaCTs had been published at the moment of market authorization, 59% after 1 year, 78% after 2 and 83% after 3 years. Most of the rest of the studies remained unpublished after 3 years of follow-up. Unpublished RaCTs differed from published trials of the same medicine especially regarding therapeutic use and/or comparator. In some cases unpublished trials have influenced the risk : benefit asssessment of the registration authorities.
Conclusions: Most of the main RaCTs, relevant for assessing the added value of a new medicine, are published subsequent to market entry; some of these trials remain unpublished. We argue for a standardized public registration of the results of the main premarketing clinical trials as a condition for market authorization.