Abstract Background Following our previous investigation of 456 articles published by the IHU-Méditerranée Infection (IHU-Mi) institute in Marseille, France, subsequent editorial actions, institutional reviews, and reports from French authorities provided additional evidence relevant to our concerns. We therefore extended our investigation to the broader IHU-Mi bibliography to assess potential breaches of the Declaration of Helsinki, French regulations governing research involving human participants, and the consistency between reported studies and the ethics approvals cited. Methods We assessed 2,674 IHU-MI publications identified through PubMed, Google Scholar, PubPeer, and manual searches. We excluded articles not reporting research involving human participants, articles clearly reporting retrospective studies without ethics flaw, and articles for which editorial investigations had clarified our concerns. We compared the remaining articles with the relevant French legal framework and, where available, with ethics approvals obtained through public transparency procedures or other sources. Results We identified ethical or legal concerns in 853 articles from this institute. These included at least 75 articles with retrospective approvals, 194 describing research conducted abroad without mention of local approvals, 343 not mentioning ethics approval, and 426 describing sample collection from healthy volunteers with concerns. Among 374 articles for which we obtained the cited ethics approval documents, at least 304, or 81.3%, described sample collections that were not covered by the corresponding approval. Since our previous investigation, editorial and institutional responses have led to 64 retractions and 270 expressions of concern, and have clarified or substantiated many of the concerns raised. We also found that the local ethics committee issuing most of the approvals may not have been sufficiently independent from the authors. Conclusion Institutional reports and editorial decisions have substantiated many of the concerns identified in our analysis, although a small subset of cases was attributable to unintentional errors. Our findings indicate widespread and longstanding problems in research ethics compliance within the IHU-Mi bibliography and support the need for continued editorial and institutional review.

The practice of clinical research is strictly regulated by law. During submission and review processes, compliance of such research with the laws enforced in the country where it was conducted is not always correctly filled in by the authors or verified by the editors. Here, we report a case of a single institution for which one may find hundreds of publications with seemingly relevant ethical concerns, along with 10 months of follow-up through contacts with the editors of these articles. We thus argue for a stricter control of ethical authorization by scientific editors and we call on publishers to cooperate to this end. We present an investigation of the ethics and legal aspects of 456 studies published by the IHU-MI (Institut Hospitalo-Universitaire Méditerranée Infection) in Marseille, France. We identified a wide range of issues with the stated research authorization and ethics of the published studies with respect to the Institutional Review Board and the approval presented. Among the studies investigated, 248 were conducted with the same ethics approval number, even though the subjects, samples, and countries of investigation were different. Thirty-nine (39) did not even contain a reference to the ethics approval number while they present research on human beings. We thus contacted the journals that published these articles and provide their responses to our concerns. It should be noted that, since our investigation and reporting to journals, PLOS has issued expressions of concerns for several publications we analyze here. This case presents an investigation of the veracity of ethical approval, and more than 10 months of follow-up by independent researchers. We call for stricter control and cooperation in handling of these cases, including editorial requirement to upload ethical approval documents, guidelines from COPE to address such ethical concerns, and transparent editorial policies and timelines to answer such concerns. All supplementary materials are available.

We, as scientists, doctors, or concerned citizens, demand the establishment of an independent scientific inquiry commission to evaluate these breaches and determine the necessary actions. At a minimum, we hope that those responsible for these serious ethical, scientific, and managerial failings will be removed from teaching, leadership, and supervisory roles to prevent the spread of these harmful research practices to young researchers and other research teams. The reputation of French research has already suffered significant damage due to these deviant practices and their tragic consequences. This global scandal, passively observed by supervisory bodies, governments, and the administration of Aix-Marseille University, has directly and indirectly cost many human lives. It is intolerable that empty statements and half-measures continue to prevail. The time has come for strong, exemplary, and coherent actions that meet societal expectations and address the stakes at hand. The French scientific community, supported by a truly independent commission, must take responsibility and determine the appropriate sanctions for these grave breaches, which sometimes border on criminal conduct.

On October 30th, a new study from the Institut Hospitalo-Universitaire Méditerranée Infection (IHU-MI) was published in the journal “New Microbes and New Infections” [1]. This is the latest publication in a long series that is controversial both scientifically and legally.Indeed, several other articles had been published by this team on the topic of Covid-19. The first one [2], has been adjudicated to be fraudulent by the former President of the board of this institute [3]. Further COVID-19 research has had significant ethical concerns arise, regarding the conduct of the studies [4,5,6,7,8] due to their purported retrospective nature despite the trial description appearing to be a prospective trial. These trials are also prima facie problematic because, from May the 11th 2020 and the removal of a special decree authorizing it temporarily, the use of hydroxychloroquine was forbidden outside of clinical trials in France, and these were not conducted as clinical trials. Similarly, off-label prescription was not possible in that case because this process is subject to a strict law regulation in France and can be proposed to patients only if: i) there is no alternative labeled therapy, ii) it is used case by case and not systematically for all patients as was the case at the IHU and iii) the available scientific data ensures efficacy and safety of the drug in the dedicated indication (see Code de la Santé Publique, Article L5121-12-1-2), which was clearly not the case for hydroxychloroquine in COVID-19 treatment. Consequently, since hydroxychloroquine is considered in this indication as an experimental drug in France, a retrospective design likely contravenes French law on biomedical research (see Code de la santé publique, Article L1121-1) [9].Despite all scientific and ethics arguments having been brought to the attention of the editor, and the publisher themselves declaring that the study has no scientific merit and is “fully irresponsible” [10] even prior to the fraud being uncovered, the initial publication has still not been retracted [11].

Recently, an article by Seneff et al. entitled “Innate immunosuppression by SARS-CoV-2 mRNA vaccinations: The role of G-quadruplexes, exosomes, and MicroRNAs” was published in Food and Chemical Toxicology (FCT). Here, we describe why this article, which contains unsubstantiated claims and misunderstandings such as “billions of lives are potentially at risk” with COVID-19 mRNA vaccines, is problematic and should be retracted. We report here our request to the editor of FCT to have our rebuttal published, unfortunately rejected after three rounds of reviewing. Fighting the spread of false information requires enormous effort while receiving little or no credit for this necessary work, which often even ends up being threatened. This need for more scientific integrity is at the heart of our advocacy, and we call for large support, especially from editors and publishers, to fight more effectively against deadly disinformation.

The practice of clinical research is strictly regulated by law. During submission and review processes, compliance of such research with the laws enforced in the country where it was conducted is not always correctly filled in by the authors or verified by the editors. Here we review 456 studies published by the IHU Méditerranée Infection (Marseille, France) and identify a range of issues with the stated authorization of the research, ethically and potentially legally. Of these, 248 were conducted with the same ethics committee reference, even though the subjects, samples and countries were different. Thirty-nine did not even contain a reference to the ethics committee while they contain research on human beings. With this example, we call for stricter control by publishers of the regulatory documentation related to clinical research during the publication process. All supplementary materials are available on https://osf.io/ueqf8/.

We share a Letter of concern To the Editor from Food and Chemical Toxicology about a recent published review from Seneff. et al entitled "Innate immune suppression by SARS-CoV-2 mRNA vaccinations: The role of G-quadruplexes, exosomes, and MicroRNAs"( doi: 10.1016/j.fct.2022.113008). In our opinion, this article contains several assumptions and misinformation that we highlight. We believe that a rapid analysis of the key points and the misinterpretations that they contain are sufficient to invalidate the relevancy of the article and therefore we ask the editor to revise their opinion on the publication of the article.

We alert in this position paper the scientific community against the dissemination of pseudoscience in apparently sane scientific journals, and the dangers that such aspreading are causing to public health. Seneff et al. recently published in Food & Chemical Toxicology a series of fallacious arguments against Covid-19 vaccination.The important shortcomings and misusage of scientific literature and data have no place in a scientific journal. Therefore, we explain why this article should be retracted inan effort to prevent further damages to health care policies.

Recently, Sun et al. published an article in Scientific Reports entitled: “Increased emergency cardiovascular events among under-40 population in Israel during vaccine rollout and third COVID-19 wave” [2]. In this paper, the authors highlighted correlations between the Israeli vaccine campaign and an increased number of severe cardiovascular event calls to Emergency Management Services in the under-40 population. Even if the correlation seemed statistically significant, it is, to our opinion, clinically irrelevant.

Here we take position against a misleading published review and explain why we ask for retraction, which should be part of the scientific debate.

Homeopathic vaccines are licensed in many countries but scientific data to support their use are sparse. The goal of this study was to compare the antibody response of homeopathic and conventional vaccines and placebo in young adults. We hypothesized that there would be no significant difference between homeopathic vaccines and placebo, while there would be a significant increase in antibodies in those received conventional vaccines.A randomized blinded placebo-controlled trial was conducted where 150 university students who had received childhood vaccinations were assigned to diphtheria, pertussis, tetanus, mumps, measles homeopathic vaccine, placebo, or conventional diphtheria, pertussis, tetanus (Tdap) and mumps, measles, rubella (MMR) vaccines. The primary outcome was a ≥ two-fold increase in antibodies from baseline following vaccination as measured by ELISA. Participants, investigators, study coordinator, data blood drawers, laboratory technician, and data analyst were blinded.None of the participants in either the homeopathic vaccine or the placebo group showed a ≥ two-fold response to any of the antigens. In contrast, of those vaccinated with Tdap, 68% (33/48) had a ≥ two-fold response to diphtheria, 83% (40/48) to pertussis toxoid, 88% (42/48) to tetanus, and 35% (17/48) of those vaccinated with MMR had a response to measles or mumps antigens (p < 0.001 for each comparison of conventional vaccine to homeopathic vaccine or to placebo). There was a significant increase in geometric mean titres of antibody from baseline for conventional vaccine antigens (p < 0.001 for each), but none for the response to homeopathic antigens or placebo.Homeopathic vaccines do not evoke antibody responses and produce a response that is similar to placebo. In contrast, conventional vaccines provide a robust antibody response in the majority of those vaccinated.Trial Registry: NCT 02825368.

The authors and the co-signatories of this open letter are scientists dedicated to transparency and integrity of research. We support the work needed to investigate potential errors and possible misconduct and believe the scientific community can do more to protect whistleblowers against harassment and threats. Individual researchers can provide vocal support for whistleblowers and against harassment to shift norms. Journals, funders, policymakers, and institutions can make explicit policies that protect whistleblowers and establish fair, judicious, and transparent processes for addressing potential misconduct that protect all participants. With this letter, we show our support for post-publication peer-review, to Elisabeth Bik and her work, and to all the whistleblowers that help maintain quality, honesty, integrity and trustworthiness of scientific advances.