How to improve the clinical development paradigm and its division into phases I, II and III.

Based on the observation that over the last 30 years the cost of development has risen regularly as the number of new chemical entities reaching the market has fallen, how can "savings" be made in terms of clinical development, the objective being more rapid access to a drug for medical needs that are not covered? Several instruments exist to enable innovative products to be made available more quickly: temporary use authorisations, which are not concerned by this work (ATUs), conditional marketing authorisations (MAs) and MAs under exceptional circumstances. These aspects have been taken up in the European medicines agency (EMA)'s "Road Map", which states "A key issue for Regulators will be if a more "staggered" approval should be envisaged, characterised by a better defined/more restricted population of good responders, followed by a broadening of the population post-authorisation when more "real life" data are available. In addition, maximising the value of information generated in the post-authorisation phase should be developed through the use of cohorts and other prospectively collected use data, especially in the case of conditional marketing authorisations." The rules of procedure of the Transparency Commission for their part provide for the notion of preliminary examination: in order to prepare as best as possible the examination of dossiers of products assumed to be innovative and to limit delays, the office can undertake a preliminary study as soon as the dossier has been filed at the Committee for medicinal products for human use (CHMP). It may, at this time, request the firm to provide further information and may call on external experts. The implementation of this preliminary study does not exonerate the firm of the obligation of filing a complete dossier. The post inscription studies requested by the Transparency Commission (ISPEP - public health benefit and post-marketing studies) are usually requested in the case of hesitations regarding the level of improvement of the medical benefit (ASMR) [level II/III or IV/V]. Such requests mainly concern uncertainties regarding the transposability, the patient profile or correct usage in real life. Among the studies whose results were provided, in 15 cases the results were in line with expectations, in 6 cases they resulted in downward re-evaluations and the final 3 cases were inconclusive. The final recommendations of the round table were: Defining the medical need that is not covered by working in consultation (Industry and Health Authorities); Providing a Complementary Investigations Plan (PIC) after the MA at a very early stage to reinforce the early MA, and/or HTA (health technology assessment) preparation and monitoring (possible constraining actions); Enhanced use of modelling techniques and their transposability; "Intussusception" of phases to optimise the development of a complete dossier; Early "scientific opinions" (EMA, French Health Products Safety Agency [Afssaps], French Health Authority [HAS]); Raising the awareness of the authorities, industry, doctors and patients with regard to controlled observational studies; Developing the use of public data bases.

Direct cost-modeling of rheumatoid arthritis according to disease activity categories in France.

OBJECTIVE: The objective of this cost-of-illness study was to assess the use of direct medical resources, excluding drug costs, by patients with rheumatoid arthritis (RA) in France, and to construct cost estimates according to level of disease activity. METHODS: Three categories of RA disease activity were defined according to Disease Activity Score 28-joint count (DAS28) thresholds: remission (DAS28 < 2.6), low disease activity state (LDAS; i.e., DAS28 ≤ 3.2), and moderate to high disease activity (MHDAS; i.e., DAS28 > 3.2). Eight resource utilization items were defined: medical visits, laboratory tests, hospitalization, imaging, physiotherapy, nursing, adaptive aids, and transportation. Resource utilization and unit costs from the national-payer perspective were estimated through expert opinion and simulated using distribution ranges for each item. Cost distributions were computed by Monte-Carlo simulations estimating overall costs per 6 months over a 2-year period. RESULTS: For patients achieving remission, costs were estimated at a mean of €771 (SD 199) for the first 6 months and at €511 (SD 162) for each subsequent 6-month period. For patients achieving LDAS, costs were estimated at €905 (SD 263) for the first 6 months and €696 (SD 240) for each subsequent 6-month period. For patients in MHDAS, costs were estimated at €1215 per 6 months (SD 405). CONCLUSION: This cost-of-illness assessment provided current estimates of direct medical costs for RA according to disease activity in France. The findings suggest that achieving remission or LDAS is associated with substantially lower medical costs for RA versus being in MHDAS.

Value of post-registration studies for reimbursement renewal.

Post-registration studies describe parameters of real-life clinical practice such as the treated population, conditions of treatment initiation, treatment duration, adherence, associated benefits/risks as well as the impact on treatment strategies, healthcare procedures and on public health. The results of these studies are used in particular for re-evaluation, re-registration or in applications for reimbursement. Since 1997, 134 requests for post-registration studies have been made either by the French Transparency Committee (CT) and/or the Committee for Pricing of Healthcare Products (CEPS) and the results of these studies were taken into account in the re-evaluation of Actual Benefit (AB) or Improvement in Actual Benefit (IAB). During the roundtable discussion on this subject at the National Clinical Pharmacology Meeting held at Giens (France), the difficulties in performing such studies were identified and proposals were made to predict and anticipate requests for these studies but also for the training of physicians.

The cost of treating high blood pressure in general practice in France.

In this study, the cost of having high blood pressure treated by French general practitioners was estimated, using an analysis of the computerized records for 28,015 patients with either hypertension or history of hypertension over three years. Costs due to visits, drugs, and complementary tests were included. The average annual cost of treatment was 597 euros (SD 377 euros). The annual average cost of drugs was 447 euros, and antihypertensive drugs 258 euros. The average annual cost of patients who were controlled throughout the period was 537 euros, patients who were normalized cost 595 euros, and patients who deteriorated cost 612 euros.