Regulatory system

How to Improve the Clinical Development Paradigm and its Division into Phases I, II and III

¹ Laboratoire Bristol Myers Squibb, Rueil Malmaison, France
² Service de Pharmacologie, Université Victor Segalen, Bordeaux, France
³ Afssaps, Saint Denis, France

Correspondence and offprints: Nicholas Moore, Service de Pharmacologie, Université Victor Segalen, Zone Nord, Bat 1A, CHU de Bordeaux, 33076 Bordeaux Cedex, France. E-mail: nicholas.moore@pharmaco.u-bordeaux2.fr

Received: 9 May 2011
Accepted: 19 May 2011

Abstract

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.