This article describes several cohorts used for the analysis. One of the cohort describes a study approved by the Ethics Committee of the IHU Méditerranée Infections under the number 2020-021. This number covers one protocol only. According best practices, one ethics approval number concern only one study and one protocol. All publications can be considered related to the same study and the same protocol. In France, the ethics committee of the IHU has not the ability to approve prospective study in human. Prospective study in human must be approved by a Comité de Protection des Personnes.
The article describes this cohort as follows:
"CASE-CONTROL study. All comers spontaneously presenting at a general hospital for infectious diseases (IHU Méditerranée Infections, Marseille, FR) (Table S1) from February 27th, 2020 to December 15th, 2020 composed of 996 COVID-19 patients. We performed a case-control study at a 1:2 paired ratio where the 175 cancer patients (with a currently treated cancer or history of cancer) were matched with 350 cancer free individuals on age, gender, comorbidities relevant for COVID-19. Of note, >75% received hydroxychloroquine and >96% received azithromycine (Table S1) (Amrane et al., 2020; Lagier et al., 2020). This study was approved by the IHU Méditerranée Infections review board committee (Méditerranée Infection N°: 2020-021)."
Considering the ethics committee of the IHU Mediterranée infection can not approve a prospective study, the assumption that this study is retrospective can be made.
We found the same Ethics committee approval number (2020-021) in 2 other papers.
This study has been approved by the same Ethics committee with the same approval number. It describes a retrospective collection of the data: "Data presented herein were collected retrospectively from the routine care setting using the electronic health recording system of the hospital. This non-interventional retrospective study was approved by our institutional review board committee (Mediterranée Infection N°: 2020–021)."
Collection of the data was made between March and April 2020:
"Data were collated from all patients from March 3rd to April 27th and were analysed retrospectively."
This article has been received by the Editor the 27 May 2020. Based on this date it can be supported that the Ethics committee approval was obtained prior to May 2020.
Based on this definition, a retrospective study uses existing data that have been recorded for reasons other than research.
It can be assumed the protocol approved with the number 2020-021 can only cover existing data and not new data to be collected after May 2020.
However, in the article "Prolonged SARS-CoV-2 RNA virus shedding and lymphopenia are hallmarks of COVID-19 in cancer patients with poor prognosis", the article describes a cohort where data was collected after the ethics committee approval (in May 2020?) and up to December 2020.
Can the authors clarify if the study 2020-021 was prospective or retrospective ? If the study was prospective, it seems that the Ethics Committee of the IHU did not have the ability to approve this study. In this situation, reusing this cohort in the article "Prolonged SARS-CoV-2 RNA virus shedding and lymphopenia are hallmarks of COVID-19 in cancer patients with poor prognosis" raises some ethical concerns.
As the protocol approved by the number 2020-021 describes a protocol using an experimental treatment for Covid19, it seems really important to clarify if:
There is some evidences that the protocol is not a standard routine care and that the study is a prospective study. Indeed, the number 2020-021 was used in a third study (see below)
Preprint "Living SARS-CoV-2 in feces suggesting possible fecal-oral contamination"
This preprint describes a study which seems to present a prospective design. The Pre-print dont mention that the stool was collected as a rountine standard care. Of note, it is difficult to consider that collecting stools sample is part of a routine standard care for covid19. Especially considering the ethics consent have been provided in accordance with the Declaration of Helsinki which requires the informed consent for study with a prospective design
"Ethical approval : The protocol was approved by the ethical committee of the University Hospital Institute Méditerranée Infection (N°: 2020-01).
Informed consent: All subjects provided informed consent in accordance with the Declaration of Helsinki."
In the pre-print, this paper is related to another protocol (2020-01) on Hydroxychloroquine and Azithromycine where concerns have also been raised on the nature of the study (observational/interventional, prospective/retrospective - see "Covid-19: care protocols or research protocols?"
Surprisingly, the final version of the article will modify the Ethics approval number and will link this paper to the protocol approved under the number 2020-21
In the final version, the ethics statement has been changed and the ethics approval number was changed by authors from 2020-01 to 2020-021:
All samples were collected as part of the diagnosis and follow-up of patients for COVID-19, and the study was approved by the ethical committee of the University Hospital Institute Méditerranée Infection (N°: 2020-021)
Any mention to the Helsinki Declaration or the informed consent obtained prior the study and which describes a prospective design, has been deleted in the final version.
Following this final version, this paper is related to the same cohort, the same study and the same protocol approved unde the number 2020-021.
Considering all these points, it would be in the interest of the scientific discussion to:
As the paper "Prolonged SARS-CoV-2 RNA virus shedding and lymphopenia are hallmarks of COVID-19 in cancer patients with poor prognosis" are using this cohort for the analysis, it is the responsibility of the author to ensure the study has been collected in accordance with the requirements of the Helsinki Declaration.
In October 2023, ANSM (French Medicines Agency) provides the following statement on its website:
"The ANSM (French National Agency for the Safety of Medicines and Health Products) once again referred the matter to the criminal prosecutor last June after becoming aware of the preprint of a scientific article presenting the results of a study on over 30,000 patients with Covid-19 treated with hydroxychloroquine and azithromycin. This study should have received a favorable opinion from an ethics review board (Comité de Protection des Personnes or CPP) and authorization from the ANSM to be implemented."
ANSM refered to the following preprint and article:
On the pre-print, the article mentions the IHU ethic approval number 2021-007 and 2021-015. The final article in NMNI only mentions the ethics approval number 2021-015.
The IHU ethics approval 2021-015 mentions a recruitment of participants starting in March 2020 and was supposed to end in May 2021. Nevertheless, the cohort continues until at least December 2021 as described in the article ” Outcomes after early treatment with hydroxychloroquine and azithromycin: An analysis of a database of 30,423 COVID-19 patients”.
Several articles describe the use of the same cohort, with the same starting enrolment period and the same participants. Results of these articles describe interim results.
In ANSM opinion, it is clear that all articles this cohort that started to enroll in March 2020, are describing an interventional study that has not obtained the proper approvals from ANSM and a certified ethics committee (Comité de Protection des Personnes) as required by the French Law. This situation is a serious deviation from the Helsinki Declaration requirements.
ANSM considered it is a possible infringement of the ethics principles and the French law. ANSM has alerted the Prosecutor for a possible criminal offense.
Based on ANSM website, the new Director of IHU Marseille and the Director of APHM (Hospital Network) received the ANSM statement and the ANSM inspection report. Nevertheless, these institutions did not have publicly claimed their intention to request the retraction of all articles using this unauthorized cohort.
Editors policies are usually aligned with the Helsinki Declaration. Based on ANSM statement and the Helsinki Declaration, Editors might reconsider the publication of all articles using this cohort and assess if retractions are required, even if not requested by the authors’ institutions.
The 19 articles below are using the same participants from the same cohort, enrolled from March 2020 for an interventional study that has not obtained the ANSM and a CPP approval. These articles describe interim results obtained at different timepoints of the enrollment.
Articles using IHU ethic approval number 2021-007 and/or 2021-015:
Articles using IHU Ethic approval number 2021-007:
Articles using IHU ethics approval 2020-021:
Articles using ethics approval 2020-01:
No ethics approval number provided:
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