In 2015 during the EBOLA crisis Yazdan Yazdanpanah, Jean-Francois Delfraissy, Yves Levy, Peter Horby wrote in The Lancet that in a humanitarian emergency,
“Randomized clinical trials (RCTs) are a bad solution ».
In your speech in March 2020 you stated on several occasions that we are in health war against the virus and consequently in an unprecedented economic war.
Given the circumstances, logic would dictate that the Scientific Committee (SC) apply the same rules as those they described in the article they published in November 2015 in the prestigious journal The Lancet.
As defined in 1990 (Appendix 1) by Lanini, the rigidity of randomized clinical studies (RCTs) makes them unsuitable for AIDS trials, and non-RCTs could be considered in the following situations:
Criterion 1: Sufficient experience to ensure that patients who do not receive treatment will have a uniformly poor prognosis.
Criterion 2: No other appropriate treatment to be used as an alternative or a witness.
Criterion 3: Nosignificant side effects expected.
Criterion 4: Justified expectation that the potential profit will be enough important to make the interpretation of a non-RCT unambiguous.
Criterion 5: The scientific justification for the treatment must be strong enough for a positive result is widely accepted.
Yazdanpanah, Delfraissy, Levy and Horby wrote about Ebola in 2015:
- The epidemic clearly fulfills the first and second criteria, as the death rate is high.
- The third criterion was satisfied for most of the strategies studied.
- Regarding criterion four, our approach was to sort the treatments between those with no effect that should be eliminated quickly, among those with obvious advantages who should be deployed immediately,
- And those promising ones that need to be evaluated in an RCT, in which a combination of antivirals could also be studied.
- This strategy is also more acceptable to patients, physicians and local communities.
The Director General of Health has made it clear on several occasions that there is a health emergency and there is a excess mortality which was presented by INSEE and picked up by all the media.
In addition, the Minister of Health and the Prime Minister foresee a second wave, as shown in the graph below with increases in the number of deaths. And to date three countries have curves that no longer go down or go up. These three countries (the United States, France and Spain) have the most severely forbidden prescription of hydroxychloroquine by doctors.
Three countries have curves which constantly descend, Sweden, or are stable; Switzerland and Germany. Moreover these three countries are among those which have the least confined
And the R0 reproduction rate is over 1 in most European countries.
In your speech of July 14, you said:
“The French ask us to treat them”, but “it is not for a politician to decide” the question of the treatment of Covid-19.
In addition on August 20 from Brégançon you declared:
“We have a reasonable outlook to have a vaccine in the next few months”, and “This is not going to fix the problems of the next few weeks, but for the next few months ”.
If it is not for the politician to decide, we can legitimately think that it is therefore for “the expert” to do so. And therefore to the Scientific Committee to advise, specifying of course that decisions are taken objectively and without conflicts or links of interest of each of these members.
We recall that Yves Levy is the former leader of INSERM, former of the Council of State; Jean Francois Delfraissy is president of the Scientific Committee; Yazdanpanah, former Gilead Board member is now a member of REACTing, Discovery, OMS and the Scientific Committee; and Peter Horby, Chief Investigator of the UK Clinical Trial Recovery cited many times as the gold standard of research. Each of these individuals has numerous links of interest with pharmaceutical companies including Gilead, which manufactures remdesivir, a drug which recently received temporary authorization for use even though it has serious side effects without proven patient benefit on the reduction. the probability of death.
In any case, the Scientific Committee, at the dawn of a possible second wave, has no reason to advise you by not using the criteria and the rationale that they themselves wrote in 2015. Otherwise, it would be a contradiction that they should explain.
Without any controversy around barrier gestures and masks, we accept that each situation is different. For the prophylactic and therapeutic medical field, by learning on the one hand the experiences of others at the level of macro health decisions, the latest studies and in anticipation of uncertainty as to possible vaccines and mutations, hypocrisy over hydroxychloroquine shouldn’t it stop?
2015 Lancet article translated into French.
Drug evaluation in the Ebola virus disease outbreak in West Africa
Authors: Yazdan Yazdanpanah, Peter Horby, Johan van Griensven, France Mentre, Vinh-Kim Nguyen Jean Marie Denis, Malvy Jake Dunning, Daouda Sissoko, Jean-François Delfraissy, Yves Lévy
Posted: November 2015 DOI: https://doi.org/10.1016/S1473-3099(15)00344-8
In their personal perspective, Simone Lanini and colleagues have argued that an adaptive randomized controlled trial (RCT) is the optimal solution for evaluating experimental treatments for Ebola virus disease and that non-RCTs are “profoundly contrary to ethics ”.
Lanini and colleagues distinguished study designs of investigational agents as randomized and non-randomized studies, including in recent anecdotal and compassionate use experiments. It is irrational not to distinguish between phase 2 clinical trials and compassionate treatment. Our group studies, also cited by Lanini and colleagues, are fully regulated Phase 2 clinical trials with explicit study frameworks.
Additionally, we have investigated interventions that have been approved by regulatory authorities for use in humans and only implemented after full ethical review and approval. Clinical trials of drugs can only be done legitimately with the consent of individuals and communities. We worked with communities to facilitate open dialogue and partnership, which shows that RCTs would not have been accepted by the time the trials were launched.
In 1990, recognizing that traditional approaches to clinical trial processes were unnecessarily rigid and unsuitable for studying treatments for HIV, Byar and colleagues 2concluded, in their paper design considerations for AIDS trials, that non-RCTs could be considered in the following situations. First, “there must be sufficient experience to ensure that patients who do not receive treatment will have a uniformly poor prognosis.” Second, “there must be no other appropriate treatment to use as a witness.” Third, “you should not expect the therapy to have significant side effects.” Fourth, “there must be a justified expectation that the potential benefit to the patient will be great enough to make the interpretation of a non-RCT unambiguous.” Fifth, “the scientific rationale for treatment must be strong enough for a positive result to be widely accepted”.
The Ebola outbreak clearly meets criteria one and two, as the death rate is high. The third criterion was satisfied for most of the strategies studied. Regarding criterion four, our approach was to sort the treatments into those with no effect that should be eliminated quickly, those with clear benefits that should be rolled out immediately, and those showing promise that should be evaluated in an RCT, in which a combination of antivirals could also be studied. This strategy is also more acceptable to patients, physicians and local communities.
A debate on the design of clinical trials during humanitarian crises is necessary, but it must be based on a precise characterization of events and problems.
YY reports personal expenses of AbbVie, BMS, Gilead, MSD, Roche, Johnson & Johnson, ViiV Healthcare, Janssen and Pfizer outside of the submitted work. All other authors declare no competing interest.