RESUMO
Background: Many established products (EPs - marketed for eight years or more) are widely used off-label despite little evidence on benefit-risk ratio. This exposes patients to risks related to safety and lack of efficacy, and healthcare providers to liability. Introducing new indications for EPs may represent a high societal value; however, manufacturers rarely invest in R&D for EPs. The objective of this research was to describe incentives and disincentives for developing new indications for EPs in Europe and to investigate consequences of current policies. Methods: Targeted literature search and expert panel meetings. Results: Within the current European-level and national-level regulatory framework there are limited incentives for development of new indications with EPs. Extension of indication normally does not allow the price to be increased or maintained, the market protection period to be extended, or exclusion from a reference price system. New indication frequently triggers re-evaluation, resulting in price erosion, regardless of the level of added value with the new indication. In consequence, manufacturers are more prone to undertake R&D efforts at early to mid-stage of product life cycle rather than with EPs, or to invest in new chemical entities, even in therapeutic areas with broad off-label use. This represents a potentially missed opportunity as developing new indications for EPs offers an alternative to off-label use or lengthy and expensive R&D for new therapies, opens new opportunities for potentially cost-effective treatment alternatives, as well as greater equity in patients' access to treatment options. Conclusion: There are potential benefits from the development of new indications for EPs that are currently not being realized due to a lack of regulatory and pricing incentives in Europe. Incentives for orphan or paediatric drugs have proven to be effective in promoting R&D. Similarly, incentives to promote R&D in EPs should be developed, for the benefit of patients and healthcare systems.
RESUMO
The slow reaction of French authorities to the so-called Mediator® saga in 2009 in France led to investigations that questioned the way conflicts of interest are reported. France implemented the Loi Bertrand ('Bertrand Law') in May 2013, known as the 'French Sunshine Act', with the aim of specifying the scope of disclosure obligations. This policy research reviewed the Loi Bertrand and reported case law from the French Council of State (COS) related to conflicts of interest in French Health technology assessment (HTA) opinion. The Loi Bertrand requires the publication of most of the agreements concluded between health-care professionals and companies and covers a vast range of health products. Commercial sales agreements of goods and services concluded between manufacturers and health-care professionals are a strong exception to this disclosure obligation. Six cases examined by the COS were analyzed, most of them related to the publication of guidelines or the removal of products from the list of reimbursed drugs and devices. These cases have been reviewed, as well as the impact of the ruling on reimbursement decisions. Four cases led to suspension or invalidation of decisions based on the Haute Autorité de Santé (HAS) recommendations due to conflicts of interest. In the two other cases, the HAS provided post hoc declarations of interest when required by the COS, and the COS considered the conflicts of interest as irrelevant for the decision. It appears that the COS based its decisions on two main criteria: the acknowledgement of negative conflicts of interest (a link with competitors) and the absence of declarations of conflicts of interest, which have to be presented when required by legal authorities irrespective of when they were completed (even posterior to the HAS opinion). However, the number of cases that have been decided against the HAS remains very limited with respect to the volume of assessments performed yearly. The strengthening of the regulation on declarations of interest might lead to more transparency but also to more cases decided by the COS. A new press investigation (in March 2015) related to alleged cases of conflict of interests led policy makers to amend the Bertrand Law in April 2015 and require the disclosure of amounts paid to health-care professionals by the industry.
