AIXIAL AN ALTEN COMPANY #TogetherWeCreateValue Retour AIXIAL REVIEW #8 | ZOOM | LinkedIn Facebook Twitter Share EARLY TREATMENT FOR COVID-19: PLEASE, EXPLAIN ! The recent refusal of the ANSM (Agence française de sécurité sanitaire des produits de santé)[1] to issue a temporary recommendation for use of ivermectin, also authorized in other countries such as the Czech Republic for the early treatment of COVID 19, raised questions ([2]) and punctuated the debate already widely initiated with hydroxychloroquine. No doubt, we should speak more precisely of the combat. Rather than trying to take sides and without getting into controversy, let’s try to understand each other’s arguments. First of all, let’s agree that the provision of a presumed effective and safe treatment is an urgent public health need that should not be put in competition with the availability of vaccines because, at least in the immediate future, we have a need for both. Therefore, identifying and evaluating drug candidates for early treatment has become a global research imperative, just as vaccination coverage has become a public health imperative. But to be made available to prescribers, it is still necessary for Health Assessment Agencies to give their advice and decision-makers to decide on the basis of the evidence of what these drugs can bring to patients affected by the infection and possibly, indirectly, to the entire population. Without subscribing to the need to use randomized controlled trials (RCTs) in therapy, in all circumstances, this is the case with early treatment for an infection that heals on its own in about 80% of cases. By integrating several regularly updated data sources, the COVID-NMA initiative lists clinical trials on COVID by providing the reader with an assessment of the methodological quality of the data collected https://covid-nma.com/ Consulted on May 18, the COVID-NMA site lists nearly 3,000 randomized control trials, of which 1,500 are in the recruitment phase, many of which have already been completed. We cannot therefore say that, since November 2019, when the epidemic began, researchers have remained inactive. But clearly, the number of drugs approved for the treatment of the early phase of the infection remains very low and the authorizations sometimes differ from country to country. However, what creates unease is not so much the divergence of decisions as the non-explanation of these differences. Are you informed about the reasons for accepting or refusing authorization? Me, not completely. Obviously, you have to be convinced that the treatment in question “works”. In this regard, I understand that some countries expect more of a “crucial experimentation” allowing a decision than a body of convincing arguments leading to presumptions. From the ANSM’s refusal concerning ivermectin (https://ansm.sante.fr/uploads/2021/04/01/20210401-ivermectine-courrier-reponse-ansm-31-03-2021.pdf ), we can understand that the agency does not content itself with presumptions and allows little latitude with regard to safety evidence since the drug, was it well tolerated under its usual conditions of use, aims, in the circumstances, to be used differently from what is provided for in its SPC (summary of product characteristics). Conversely, the Czech Republic, like other countries, temporarily authorizes ivermectin given its good safety profile and a potential clinical effect since March 3. To understand this difference of opinion, perhaps we should not be content to consider in a somewhat simplistic way: the treatment works or does not work? If it works, we authorize it, if it doesn’t, we don’t authorize it? But rather to subdivide the problem into two complementary questions: firstly, taking into account the data which one has, is it that “it works” or, is there a more or less important presumption that it works? Secondly: taking into account the situation of urgent need, even if one is not sure that “it will work”, is there a moment, a threshold, or arguments – not only clinical – where it is more prudent to allow than to forbid? Not assuming that the authorities as debaters have omitted to ask such questions rather, in order for us to be able to adhere to their positions, let us ask them for a transparent communication of why they made the authorization determinations that they made. Authorization is a decision to act; scientific evaluation is a prior non-decisional step that judges the evidence and its scientific quality. Yet, as we mentioned before, science does not dictate the decision. This concept, I was going to say, as old as the world, goes back at least to the Nicomachean Ethics where Aristotle tells us that the characteristic of practical knowledge is to deliberate with prudence on everything contingent, bearing on the uncertain. But prudence, he explains to us, cannot be either a science or an art but a disposition, accompanied by a true rule, capable of acting in the sphere of what is good or bad, in this case for a community. Thus, there is not in such a decision only science which tells the truth in a revisable way -there is also an ethical dimension: is such a decision good for the health of the population? In any decision to authorize the use of drugs there is a greater or lesser degree of uncertainty: uncertainty about the veracity of the evidence? its transposability in “real life”, on the net benefit that the patient can expect from it? … But in ordinary situations, especially when there is an alternative, we have time to minimize it before being able to make less questionable decisions. However, the pandemic is not an ordinary situation and we do not have time. The absence of available treatment and the urgent global need introduces a temporal dilemma mentioned in a post-precedent: to authorize therapy on uncertain evidence – at the risk of errors of assessment – or to refuse it pending more solid evidence, at the risk of a possible loss of chance for the sick…. The differences in authorizations between countries would thus arise not so much from a divergent assessment of the strength of the evidence as from a varying tolerance of the decision-maker vis-à-vis the risk taken in accepting or rejecting sub-optimal evidence. These differences have given rise to violent reactions and accusations, the peremptory aspect of which sometimes contrasts precisely with the ambient uncertainty, some accusing others of criminal madness and either of making people take reckless risks by abusing science, or on the contrary of letting the sick die when so many effective drugs available. An explanation of the Health Assessment Agencies’ deliberation for decisions phase would teach and clarify more for us than a simple judgment made in regard to the level of scientific evidence gathered. Perhaps such an explanation could reduce the current unease and place the debate in a less vague context? — Written by Jacques Massol, MD PhD, AIXIAL consultant [1] French National Agency for Medicines and Health Products Safety [2] https://ansm.sante.fr/actualites/lansm-publie-sa-decision-sur-la-demande-de-rtu-pour-livermectine-dans-la-prise-en-charge-de-la-maladie-covid-19 POST NAVIGATION CMED GROUP joins AIXIAL Group, the CRO of ALTEN Group Interview of collaborators: Dr. Jacques Massol | LET’S TALK ABOUT | AIXIAL Review #10 17.11.2021 Interview of employees: Galia 18.10.2021 ‹ › AIXIAL 4 rue Danjou – Bâtiment B 92513 Boulogne-Billancourt Cedex FRANCE T: +33 1 46 08 89 00 DISCOVER AIXIAL Discover AIXIAL ALTEN group Data protection policy AREAS OF EXPERTISE Vigilance Regulatory Affairs Clinical Data Science Clinical Operations WORK AT AIXIAL Offers Career page FOLLOW US linkedin Youtube Copyright © www.aixial.com - All Rights Reserved - Legal disclaimer SPONTANEOUS APPLICATION