Health research and innovation: Can we optimize the interface between startups/pharmaceutical companies and academic health care institutions or not?

Although France has numerous assets in the realm of health care, such as the excellence of its research teams, the reputation of its healthcare system, and the presence of many startups, all of which are necessary to become a leader in innovation, it also has combined cultural and regulatory barriers that limit the flexibility and efficiency of interactions between companies/startups and public health institutions. Therefore, the aim of the roundtable discussion was to optimize the interface between those businesses and institutions. Several institutions have successfully implemented teams and procedures which aim to facilitate this interface, with regard to assessments of technology, services provided, the transfer of biological material, R&D collaboration, and licensing agreements. However, there is still a notable absence of entrepreneurial culture among hospital and academic research practitioners; their training regarding innovation remains insufficient and business-related value-creation is non-existent in their career evolution. Pharmaceutical companies, and particularly startups, often lack knowledge about hospital environments and their constraints. As a result, the recommendations of the roundtable participants are as follows: (1) promote reciprocal acculturation between public health institutions and startups through multidisciplinary training in innovation, promoting project development and staff recognition within the institution, and improving pharmaceutical companies' understanding regarding the health care system; (2) provide those involved with means and resources dedicated to innovation by reserving time for innovation at work, securing the status of the staff involved, and aiding in the search for funding; (3) develop and use standard methodologies and tools; and (4) co-design and co-construct innovative health solutions, encouraging the emergence of participatory and interdisciplinary creative spaces. All of these recommendations should help to make the interface between startups/companies and public health institutions more fluid and attractive for those in the health sector.

Hospital-based health technology assessment in France: A focus on medical devices.

Hospital-based health technology assessment (HTA) guides decisions as to whether new healthcare products should be made available within hospital structures. Its extension to medical devices (MDs) makes it possible to analyse several relevant aspects of these healthcare products in addition to their clinical value, and such evaluations are of interest to national health authorities, other healthcare establishments and industry. The aim of this work was to formulate several recommendations for a blueprint for hospital-based HTA for MDs in France. Five themes based on the work of the European Adopting hospital-based HTA in the EU (AdHopHTA) project were defined. Each member of the roundtable was then allocated a documentation task based on their experience of the theme concerned, and a literature review was carried out. An inventory of hospital-based HTA was performed and six recommendations aiming to strengthen and improve this approach were put forward: (1) encouragement of the spread of the hospital-based HTA culture and participation in communications and the promotion of this approach to hospital decision-makers; (2) adaptation of hospital-based HTA to the needs of decision-makers, taking into account the financial timetable and strategic objectives of the healthcare establishment; (3) harmonisation of the dossiers requested from industry between healthcare establishments, based on a common core; (4) promotion of the sharing of hospital-based HTA data under certain conditions, with data dissociable from the HTA report and the use of a validated methodology for the literature review; (5) creation of a composite indicator reflecting data production effort and the sharing of HTA activities, to be taken into account in the distribution of funds allocated for teaching, research and innovation missions considered of general interest; (6) the transmission of information directly from local to national level by pioneering centres. This work highlights the major issues at stake in hospital-based HTA and the need to valorise such activities in France.

Biosimilars: from technical to pharmacoeconomic considerations. 30th Rencontres Nationales de Pharmacologie et Recherche clinique pour l'Innovation et l'Evaluation des Technologies de Santé. Tables rondes.

A biosimilar is a biological medicinal product claimed to be similar to a reference biological medicinal product. Its development plan includes studies comparing it with the reference product in order to confirm its similarity in terms of quality, preclinical safety, clinical efficacy, and clinical safety, including immunogenicity. Biosimilars differ from generics both in their molecular complexity and in the specific requirements that apply to them. Since patents on many biological medicinal products will expire within the next 5 years in major therapeutic areas such as oncology, rheumatology and gastroenterology and as those products are so costly to the French national health insurance system, the availability of biosimilars would have a considerable economic impact. The round table has issued a number of recommendations intended to ensure that the upcoming arrival of biosimilars on the market is a success, in which prescribing physicians would have a central role in informing and reassuring patients, an efficient monitoring of the patients treated with biologicals would be set up and time to market for biosimilars would be speeded up.

Information and communication on risks related to medications and proper use of medications for healthcare professionals and the general public: precautionary principle, risk management, communication during and in the absence of crisis situations.

Recent drug crises have highlighted the complexity, benefits and risks of medication communication. The difficulty of this communication is due to the diversity of the sources of information and the target audience, the credibility of spokespersons, the difficulty to communicate on scientific uncertainties and the precautionary principle, which is influenced by variable perceptions and tolerances of the risk. Globally, there is a lack of training in risk management with a tendency of modern society to refuse even the slightest risk. Communication on medications is subject to regulatory or legal requirements, often uses tools and messages that are not adapted to the target audience and is often based on a poor knowledge of communication techniques. In order to improve this situation, the available information must be coordinated by reinforcing the unique medication information website and by coordinating communication between authorities by means of a single spokesperson. A particular effort must be made in the field of training in the proper use and risk of medications for both the general population and patients but also for healthcare professionals, by setting up a unified academic on-line teaching platform for continuing medical education on medications and their proper use.

Assessment of the health risks related to the presence of drug residues in water for human consumption: application to carbamazepine.

Pharmaceutical residues have been detected at low (usually ng/L) concentrations in drinking water sources. The detection of drugs in water intended for human consumption (WIHC) has raised questions of safety. In the absence of regulatory or other official guidance, water utilities are faced with a problem of which pharmaceutical residues should be monitored and the toxicological limits that should be required. In this essay, we define an approach for the assessment of health risks related to chemicals found in drinking water. We use the examples of carbamazepine and its main metabolite 10,11-epoxycarbamazepine to demonstrate our approach, which involves application of the following algorithm: (1) when there is human or animal toxicity data, a toxicity reference value (TRV) can be calculated; (2) when this is not applicable, an attempt should be made to derive the TRV using known information about the minimum therapeutic dose (MTD); and (3) when no applicable data is available, at all, a threshold of toxicological concern (TTC) should be estimated. In the case of carbamazepine, where relevant toxicological data exists, we derived a TRV, based on the known minimum therapeutic dose (MTD). For carbamazepine's metabolite 10,11-epoxycarbamazepine, there is no toxicological data, so we applied the TTC approach. Using this approach, and combining our estimates with what is known about these chemicals' margin of exposure (MOE), suggests that there is likely to be no appreciable risk to human health exposure to carbamazepine or its major metabolite, even given the inevitable uncertainties in exposure scenarios.

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.