How can the quality of medical data in pharmacovigilance, pharmacoepidemiology and clinical studies be guaranteed?

The development of medicinal products is subject to quality standards aimed at guaranteeing that database contents accurately reflect the source documents. Paradoxically, these standards hardly address the quality of the source data itself. The objective of this work was to propose recommendations to improve data quality in three fields (pharmacovigilance, pharmacoepidemiology and clinical studies). The analysis was focused on the data and on the critical stages presenting critical quality problems, for which the current guidelines are insufficiently detailed, unsuitable and/or poorly applied. Finally, recommendations have been proposed, mainly focused on the origin of the data and its transcription.

Conflicts of interests in the area of healthcare products and technology. Current state of affairs and recommendations.

The handling of conflicts of interest in the area of healthcare products and technology has become a major issue for all of those involved in healthcare. Round Table N°4 at the Giens Workshops 2011 has put forward concrete proposals to clarify and optimise the handling of conflicts of interest. Conflicts of interest cannot be defined by the individuals consulted or applying for funds since each institution, whether public or private, that puts out a call for projects or that requests advice, analyses or expert testimony in the healthcare field has different degrees of what it defines as a conflict of interest, depending on the context of the proposal or specific request that it puts out. In contrast, each individual has ties of personal interest that can and must be openly disclosed. The ties are much more diverse than what is commonly found in the conflict of interest statements of large institutions operating in the healthcare field and are not limited to financial and operational ties between companies and individuals. In addition, the statements are difficult to manage because of their sheer number. The Round Table recommends that each individual should openly disclose all of his or her ties of personal interest in a Single Statement of Ties of personal Interest (SSTI). The SSTI would be updated regularly and accessible on line. Each institution could then determine whether or not the reported ties represent a conflict in the context of the mission proposed. Each institution could publish in advance the conditions that would give rise to a conflict and, in this way, an individual could refrain from applying for the mission. Other practical approaches to handling conflicts of interest were put forward.

[The Committee for the Protection of Human Subjects in biomedical research, crossroads of misunderstandings]. / Le Comité de protection des personnes (CPP), carrefour des quiproquos.

The conditions for carrying out clinical experiments involved numerous and serious breaches of Hippocratic morality and of the rights of people subjected to research situations. The World Medical Association has recommended the prior intervention of an independent committee "for advice and guidance" to the medical researcher. This recommendation has been taken into consideration by the competent authorities of industrially developed countries, which have incorporated structures of this type into their legislation, each having their own dispositions in this domain. In this regard, European regulations leave each member state free of their organisation. Since 1988, French legislation has set up specialised committees, whose missions have changed over time. However, the interpretations that are made by most medical researchers of the nature and roles of this institution are characterised by significant misconceptions, misunderstandings and errors in view of what arises from a legal analysis. In contrast with that the name of "ethics committee" suggests, the Committees for the Protection of Participants (CPP) do not have to comment on the ethics of the trials, but must ascertain that the sponsors and investigators organise their research protocol in compliance with the law, both with regard to the rights of the participants and the obligations incumbent on them. While it is possible for the CPPs to give an opinion on the relevance of the research, this opinion does not make them either expert committees or scientific committees. The aim of this work is to re-establish an interpretation of the role of Committees for the Protection of human subjects that conforms to the law.

[From Nuremberg to the ethics committees in human experimentation]. / De Nuremberg à aujourd'hui: les << Comités d'éthique >> dans l'expérimentation humaine.

During the Nuremberg trials, the accusation prompted the creation of an ad hoc committee to advise on human experiments carried out on prisoners during wartime in the USA. Precisely a charge that had been brought against Karl Brandt and his colleagues. This committee was the forerunner of the Independent Committees, to which the Declaration of Helsinki assigned a role in analysing the ethics of research projects in humans. From 1980 onwards, in industrialised countries, the legislation regarding clinical trials began to incorporate similar structures, IRBs in the United States of America, Ethics Committees elsewhere, and the ''Committee for the Protection of Persons" in France. However, at that time, in spite of the misleading words, we went from ethics to law, from rules of conduct intended for researchers to legal regulations organising relations between sponsors, investigators and persons participating in biomedical research, which is not the same thing.

Generics and substitution modalities: proposed methods for the evaluation of equivalence, traceability and pharmacovigilance reporting.

The use of generics results in savings for the budget of the health insurance, and no player of health could question seriously the principle. The generic drug of a reference medicinal product defines itself as a drug having the same qualitative and quantitative composition in active ingredients, the same dosage form and the bioequivalence with this reference medicinal product was demonstrated by appropriate studies of bioavailability. It is the right to switch granted to the pharmacists in 1999 that is at the origin of the real development of these specialties on the French pharmaceutical market. Nevertheless, about 10 years later, it seems that the system in place does not offer all the necessary securities with regard to pharmacovigilance, notably for the products with narrow therapeutic margin. By strengthening and/or by completing the role played by the health care professionals and the public institutions concerned, it is highly possible to improve the robustness of the system. Also, the recent arrival in Europe of the biosimilars, similar molecules but not bioequivalent to biological products, cause an even more tricky specific situation than that of the generics because of their nature, of the difficulty to manufacture them, and of the risk of immunogenicity. If the substitution is not permitted in several European countries including France, the other issues can appear especially in case of interchangeability requiring also, the reinforcement of certain measures.The various aspects are described in this article with concrete proposals on how the current system can be made safer, both for the generics and the biosimilars.

Committee for the protection of persons.

The transposition into French law of Directive 2001/20/CE, which relates to good clinical practice in the conduction of trials on drugs for human use, has required the modification of certain provisions that concern the protection of persons participating in biomedical research, in particular those provisions concerning the conditions for the authorisation of biomedical research. Declaration to the competent authorities now comes prior to authorisation and, henceforth, the prior opinion of a Committee for the Protection of Persons (CPP) must be expressly favourable in order for a trial to be undertaken. Proposals are put forward by this Round Table in order to promote the stability and professionalism of the CPPs.