Retrospective Review of Observational Data Requested by the French Health and Technology Assessment Agency: How are Results Taken Into Account?

When assessing medicinal products in order to provide recommendations for reimbursement, the Transparency committee (TC) of the French health and technology assessment agency (HAS) may ask pharmaceutical companies to provide additional data. These data are collected via observational studies called post-registration studies (PRS). We analysed how PRS final results are taken into account into TC reassessments. Final results of PRS submitted between 1996 (files computerisation) and 01/06/2016 were extracted from HAS database. For each result, have been identified: time to obtain data, integration in a Transparency Opinion and percentage of change of TC assessment criteria “actual clinical benefit (ACB)” qualified on a 4 point-scale from substantial to insufficient and “clinical added value (CAV)” qualified on a 5 point-scale from major to absent. A total of 137 PRS final results have been registered. These requests for additionnal data were more likely to affect drugs with a “substantial” ACB (79%) and a “major to minor” CAV (62%). In median, 6 years was necessary for pharmaceutical companies to provide final data. These PRS were largely field epidemiological studies (80%) with a descriptive (77 %), non-comparative (72 %) and prospective (77 %) design. Final results have been integrated in a Transparency Opinion in 91% of the cases. No change of ACB and/or CAV have been observed in 68% of the Transparency Opinion integrating PRS final results. When the ACB criteria have been modified, it was largely degraded (n=21/22) leading to an unfavorable opinion for reimbursement for 15 drugs. When the CAV criteria have been modified, it was systematically lowered (n=16/16). PRS are a significant point taken into account for the assessment of medicinal products whilst their results do not change ACB and CAV in most cases.