This is part 2 of a series describing papers from the IHUMI/AMU institutions in Marseille, France, with potential problems. In Part 1, I listed papers with image concerns. In this follow-up I’ll focus on a set of papers that might have problems with human subjects research not having received proper ethical approval. The articles span a decade of research on homeless people in Marseille, and involve different studies and specimens — but all were run under just one IRB approval number.
Research on humans requires ethical approval
In most countries, research carried out with human subjects has to be approved by an Institutional Review Board (IRB; the body’s name can vary by country, but I will use the US term here). This is a committee that reviews research proposals involving human participants, to ensure that subjects are recruited and treated fairly, to protect them from physical and psychological harm, and to make certain that the research follows all ethical rules. Overall, this makes sure that research adheres to the World Medical Association’s Declaration of Helsinki on human research ethics.
Research proposals submitted for IRB approval typically need to be specific in terms of: how many subjects will be recruited; how, when, and where they will be recruited; what type of research will be conducted; and which types of samples or data will be collected. In general, IRB approval for one study cannot be used for other research. For example, a researcher who gets IRB approval for a study recruiting 50 participants who are asked to donate a stool sample can’t use the same protocol two years later to ask other people to donate a blood sample. For IRB approval, every study needs to be described in detail. One cannot simply collect very different specimen sets under approval given for a previous study.
Research on vulnerable populations
IRB approval for a study is especially important for research involving vulnerable populations, such as prisoners, veterans, pregnant women, people with mental health problems, students, and children. In such situations, participants have to be extra-protected from any potential harm and ‘coercion and undue influence‘. Coercion means that a participant might feel they will not have access to something basic, such as health services, unless they participate; while undue influence means that participation might result in e.g. extra credits being give to a student taking part in research. The recruitment methods therefore need to ensure that subjects feel no unnecessary pressure to participate.
Of course, IRB rules might differ per country. In the US, IRB approval for research on vulnerable subjects is strictly regulated.
Since this blog post is about a set of studies on homeless persons (see more details below), let’s briefly discuss some of the ethical concerns this could raise. Homeless persons might be considered as a “vulnerable population” (i.e., vulnerable to coercion), similar to veterans or prisoners. See e.g. here, here, and here. One could imagine that if homeless persons enter a shelter and are asked to participate in a research study, they could feel pressure to participate, in order to have a bed and a meal that night. Even if participation in the study doesn’t actually influence the individual’s right to stay in the shelter, a homeless person could fear that it might, resulting in them feeling more pressure than well-intentioned researchers may have anticipated. Research protocols in such situations need to be reviewed by IRB committees to ensure that study recruits suffer no negative consequences by not participating.
Human subject research in France
In France, research involving human subjects cannot be approved by the institute itself. Since 1988, such research must be approved by one of the 39 regional Comités de Protection des Personnes (CPPs). The highest level of human research — named RIPH1 — even needs prior approval from the ANSM, the French National Agency for the Safety of Medicines and Health Products.
Despite these strict ethical rules in France, many papers produced by the Marseille IHUMI/AMU groups led by Professor Raoult appear to contain problems with the human research approval process. A July 2021 article in the French newspaper L’Express, described several Raoult group studies that appear to have been published without CPP approval. Some of these included children. The article also describes several sets of Raoult studies all run under the same approval number.
A decade of research on homeless people — all using the same IRB approval number
A set of 17 papers (see below for the full list), spanning 10 years of research on homeless people in Marseille, appear to have all been performed under the same IRB approval number, i.e. 2010-A01406-33.
Although all of these studies involved homeless people recruited from Marseille shelters, the studies themselves used very different study protocols and treatment/sample collection methods. The studies included collecting lice from subjects’ bodies; treating lice-infested subjects with drug-impregnated underwear; filling out questionnaires; medical exams; nasal and pharyngeal sampling; skin swabbing; blood draws; rectal samples; sputum collection; and chest X rays.
From the papers, it was unclear whether the same 2010-A01406-33 approval covered all these different study methodologies and sampling types.
In some of the 17 studies in this set, the IRB approval number is presented as a local, Aix-Marseille Université- or IHU-obtained, approval. In other studies, such as DOI 10.1371/journal.pone.0058088, the same number is listed as the ANSM RCB authorization ID, as per “Informed consent was obtained from these subjects, and the study was approved by the ‘‘Comité de Protection des Personnes Sud Mediterranée’’ on January, 12, 2011 (ID RCB: 2010-A01406-33)”. So perhaps the authors mixed up which committee actually approved this research.
Who approved 2010-A01406-33?
Either way, it would be helpful to know whether the 17 studies performed on this vulnerable population all fell within the original IRB approval scope. And whose approval number was this? Was it the IHU itself? One of the 37 French CPPs? Or the ANSM?
In March 2021, I emailed the CPP Sud Mediterranée to ask what type of research was covered by 2010-A01406-33, and they answered (emphasis mine): “The number RCB: 2010-A01406-33 has been given by the ANSM. It is too complicated for us to go back to our paper archives from 2010 but we can certify that this study protocol has been approved by our CPP.”
Apparently, the CPP had not heard of computers and files and PDFs in 2010, so we can only fear that our friend 2010-A01406-33 lives in a dusty box in the troisième sous-sol, in a basement deep beneath the streets of Marseille.
A similar request for more info emailed to L’Agence nationale de sécurité du médicament et des produits de santé (ANSM) initially went unanswered, but at the end of July 2021, they sent me a copy of the title page of an approval of 2010-A01406-33 dated 21 January 2011. The title of the protocol is ‘Eradication du portage du pou de corps par vêtements imprègnés de permethrine: essai comparatif versus placebo en double aveugle dans les populations defavorisées de Marseille‘ (Eradication of carriage of body lice using clothes impregnated with permethrin: a double-blind controlled trial versus placebo in underprivileged populations in Marseille).
One number to rule them all
The approval sent to me by the ANSM is only a title page with no details, but based on the study title, it seems to cover a research study that was published in 2014, i.e. Effect of Permethrin-Impregnated Underwear on Body Lice in Sheltered Homeless Persons: A Randomized Controlled Trial – JAMA Dermatol. 2014;150(3):273-279 – DOI: 10.1001/jamadermatol.2013.6398 – 2014 – [PubPeer]
In this study, registered on ClinicalTrials.gov, 125 homeless people were recruited at shelters in Marseille in order to study the effect of permethrin-impregnated underwear on body lice.
Based on the obtained 2010-A01406-33 documentation, it is unclear if the approval contained specific language to ensure that the study subjects — homeless people — were treated respectfully and felt no pressure to participate.
Of additional concern, the approval does not seem to cover body lice sampling, blood drawing, sputum collection, or rectal swabbing. Yet, 16 other studies have used this same approval number. Although most were also performed in homeless shelters in Marseille, they cover completely different studies and specimens.
List of papers using 2010-A01406-33
Below is a list of the 17 papers that mention Approval No. 2010-A01406-33 (note that Google Scholar’s search gives 21 results, but some entries are duplicates, or preprint versions). I posted concerns about all 17 papers on PubPeer on 17 March 2021, with an email sent to the corresponding author and others.
As you will see from the list, most papers deviate substantially from the original approval, i.e. the one for the 2014 study investigating impregnated underwear (marked below in bold). The papers involved intimate and invasive specimen collections from homeless subjects, including collecting head and body lice, pharyngeal sampling, blood draw, and rectal swabs.
Now, it might just be that these papers are missing important details in the text, and that the studies were actually performed according to the rules, or according to new CPP or ANSM approvals.
A simple answer by the authors could clarify such issues, but unfortunately none of the papers listed below have received author answers on their PubPeer posts.
I still await an official reply.
- Detection of a Knockdown Resistance Mutation Associated with Permethrin Resistance in the Body Louse Pediculus humanus corporis by Use of Melting Curve Analysis Genotyping – DOI: 10.1128/JCM.00808-12 – 2012 – [PubPeer] – Louse sampling; given new clothes.
- Distinguishing Body Lice from Head Lice by Multiplex Real-Time PCR Analysis of the Phum_PHUM540560 Gene – DOI: 10.1371/journal.pone.0058088 – 2013 – [PubPeer] – Louse sampling.
- Effect of Permethrin-Impregnated Underwear on Body Lice in Sheltered Homeless Persons: A Randomized Controlled Trial – DOI: 10.1001/jamadermatol.2013.6398 – 2014 – [PubPeer] – Given clean underwear treated with or without permethrin.
- Host switching of human lice to new world monkeys in South America – DOI: 10.1016/j.meegid.2016.02.008 – 2016 – [PubPeer] – Louse sampling, also from monkeys.
- Changing Demographics and Prevalence of Body Lice among Homeless Persons, Marseille, France – DOI: 10.3201/eid2311.170516 – 2017 – [PubPeer] – Questionnaire and medical exam for lice.
- Epidemiology of respiratory pathogen carriage in the homeless population within two shelters in Marseille, France, 2015e2017: cross sectional 1-day surveys – DOI: 10.1016/j.cmi.2018.04.032 – 2019 – [PubPeer] – Questionnaire, nasal and pharyngeal sampling.
- Low prevalence of resistance genes in sheltered homeless population in Marseille, France, 2014–2018 – DOI: 10.2147/IDR.S202048 – 2019 [PubPeer] – Questionnaire, nasal and pharyngeal samples.
- The Presence of Acinetobacter baumannii DNA on the Skin of Homeless People and Its Relationship With Body Lice Infestation – DOI: 10.3389/fcimb.2019.00086 – 2019 [PubPeer] – Questionnaire, medical exam, louse collection, swabs of skin, hair, neck, armpit, pelvic belt, blood sample.
- Preliminary Feasibility Study of Questionnaire-based Active Pulmonary Tuberculosis Screening in Marseille Sheltered Homeless People, Winter 2018 – DOI: 10.2991/jegh.k.190510.001 – 2019 [PubPeer] – Medical exam, sputum samples taken for TB screening.
- Enteric pathogenic bacteria and resistance gene carriage in the homeless population in Marseille, France – DOI: 10.1007/s10096-020-03889-6 – 2020 [PubPeer] – Questionnaire, physical exam, blood sample.
- Pattern of infections in French and migrant homeless hospitalised at Marseille infectious disease units, France: A retrospective study, 2017–2018 – DOI: 10.1016/j.tmaid.2020.101768 – 2020 [PubPeer] – Homeless persons in Marseille admitted to IDU hospital, regular clinical care but also a mystery control group.
- Molecular Evidence of Bacteria in Clothes Lice Collected from Homeless People Living in Shelters in Marseille – DOI: 10.1089/vbz.2019.2603 – 2020 – [PubPeer] – Louse sampling.
- Molecular investigation and genetic diversity of Pediculus and Pthirus lice in France – DOI: 10.1186/s13071-020-04036-y – 2020 [PubPeer] – Louse sampling among homeless, and patients in Bobigny hospital (including 1 school child).
- Variations in respiratory pathogen carriage among a homeless population in a shelter for men in Marseille, France, March–July 2020: cross-sectional 1-day surveys – DOI: 10.1007/s10096-020-04127-9 – 2021 [PubPeer] – Questionnaire, nasal samples.
- Enteric pathogenic bacteria and resistance gene carriage in the homeless population in Marseille, France – DOI: 10.1556/030.2021.01346 – 2021 [PubPeer] -Questionnaire, rectal samples.
- Epidemiological serosurvey and molecular characterization of sexually transmitted infections among 1890 sheltered homeless people in Marseille: Cross-sectional one day-surveys (2000–2015) – DOI: 10.1016/j.jinf.2020.11.026 – 2021 [PubPeer] – Medical exam, serum samples.
- Screening Strategy of Active Pulmonary Tuberculosis in Sheltered Homeless People in Marseille, 2019 – DOI: 10.2991/jegh.k.201009.001 – 2021 [PubPeer] – Medical exam, Chest X ray, sputum samples taken for TB screening.