11 PhD Candidates Working on Research Projects in Epidemiology and Public Health
The research team Epilogy, Epidemiology and Evaluation of Therapeutics in Dermatology and Immune-Mediated Inflammatory Diseases currently hosts 11 PhD candidates working on research projects in epidemiology, public health, and therapeutic evaluation.
Their work focuses in particular on large-scale health data analysis, treatment effectiveness and safety evaluation, and the development of advanced methodological approaches applied to dermatological diseases and immune-mediated inflammatory diseases.
These doctoral projects contribute to improving the understanding of disease mechanisms, refining therapeutic strategies, and generating robust scientific evidence to support clinical research, public health decision-making, and better patient care.
Enrollment 2025
Real-world evaluation of targeted combination therapies in chronic inflammatory diseases
PhD candidate in Public Health
Supervisor: Patrick Maison, Emilie Sbidian
Funding: ANSM
Doctoral thesis
The increasing use of targeted combination therapies in IMIDs raises new and crucial questions about their safety and efficacy in real-world settings. Although these strategies have the potential to improve clinical outcomes, they may be associated with an increased risk of serious adverse events, such as opportunistic infections, cardiovascular events, and cancers.
The objectives of this thesis are to:
- Describe patterns of use of targeted combination therapies in IMIDs.
- Evaluate the real-world efficacy of different therapeutic strategies (monotherapy vs. targeted combination therapy) for the most common indications.
- Identify and quantify potential new signals of adverse events associated with targeted combination therapies in IMIDs.
Use, safety and efficacy of human papillomavirus (HPV) vaccines in France
PhD candidate in Public Health
Supervisor: Rosemary Dray-Spira
Funding: ANSM
Doctoral thesis
Vaccination against human papillomaviruses (HPV) aims to prevent HPV infections and related diseases, in particular cervical, genital and ENT cancers. In France, vaccination has been recommended and reimbursed for all young girls since 2007 and for boys since 2021, but vaccination coverage in 2022 was well below the 80% target set by the 10-year cancer control strategy. Furthermore, although the safety profile of HPV vaccines is now well established, the hypothesis of a rare but increased risk of Guillain-Barré syndrome following vaccination needs to be investigated in new studies involving large populations. Finally, given the limited time available since the introduction of HPV vaccination, data on its real-life efficacy are still limited.
The aim of this work is to provide information to better characterize the use, safety and efficacy of HPV vaccination in the context of the vaccination program implemented in France between 2007 and 2023.
More specifically, the aim is to:
- Identify the characteristics of people vaccinated in France between 2007 and 2023.
- Measure the risk of Guillain-Barré syndrome in association with HPV vaccination.
- Measure the efficacy of HPV vaccination on the risk of cervical cancer for all girls/women vaccinated in France between 2007 and 2023.
The work, based on exhaustive data from the French National Health Data System (SNDS), will cover the entire population concerned by the HPV vaccination program between 2007 and 2023, distinguishing between those who have been vaccinated and those who have not based on reimbursement data from the SNDS. Various methodological approaches will be considered to measure the association between HPV vaccination and the risk of Guillain-Barré syndrome, including the self-controlled case series (SCCS) method. The efficacy of vaccination on the risk of cervical cancer will be measured using Cox or Poisson models, taking into account socio-demographic characteristics, health status indicators, and level of use of the healthcare system.
Long-term safety of treatments used for Assisted Reproductive Technology (ART) for mother and child
PhD candidate in Public Health
Supervisor: Rosemary Dray-Spira
Funding: ANSM
Doctoral thesis
The long-term safety of the various treatments used during ART is still poorly understood, with many questions remaining about their possible association with the onset of cancers, particularly hormone-dependent cancers in women, and with malformation and neurodevelopmental risks in children. Further work on large populations is therefore needed to assess the long-term risk of specific treatments used during ART for both mother and child, especially given the expansion of access to a large part of the population under recent bioethics laws.
The thesis work will aim to meet three objectives:
- Characterize the risks of major congenital malformations associated with maternal exposure to hormone treatments used for ART.
- Characterize the risks of neurodevelopmental disorders associated with maternal exposure to hormone treatments used for ART.
- Characterize the risks of hormone-dependent cancers associated with exposure to hormone treatments used for ART.
The work will be based on data from the National Health Data System (SNDS). To meet objectives 1 and 2, data from the EPI-MERES registry, which includes all pregnancies completed in France since January 2010 and the children born from them, will be used. The risks of major congenital malformations and neurodevelopmental disorders will be compared between children born after ART, considered as a whole and separately according to the type of ART and the hormone treatments received by the mother for ART, and those born from pregnancies without ART.
To meet objective 3, all women for whom ART has been identified in the SNDS since 2010 will be included in this study, regardless of whether the ART was followed by a pregnancy or not. The risks of developing hormone-dependent cancer (breast, uterine, ovarian, or thyroid cancer) will be compared between women who have undergone ART, considered as a whole and separately according to the hormone treatments received for ART, and those who have not undergone ART. The analyses will take into account other risk factors for hormone-dependent cancers (in particular, sociodemographic characteristics, comorbidities, and co-medications).
Enrollment 2024
Examining the Impact of ‘Salami-Slicing’ and Redundant Publications on Evidence Quality in RCTs and Systematic Reviews of Inflammatory Diseases
PhD candidate in Public Health
Supervisor: Laurence Le Cleach
Funding: doctoral contract
Doctoral thesis
The growing number of new therapies and studies evaluating Immune-mediated inflammatory diseases (IMIDs), followed by increasing number of publications on drug treatment and efficacy, calls for rigorous synthesis and methodological appraisal of the available evidence. The quality of these publications remains controversial, as many of them are “secondary publications”, which often face criticism for redundancy and “salami-slicing” – the fragmentation of a single trial’s findings into multiple reports that could have been consolidated into one coherent report. Because secondary outcome reports are usually not aligned with an RCT’s primary reporting plan, selective outcome reporting bias may be present, which occurs when studies do not provide the results for all measured outcomes or selectively report only some of the analyses undertaken with favorable results.
Research indicates that 90% of secondary publications include at least one statistically significant finding, most of which are derived from subgroup analyses or pooled results. Secondary publications, with possible practice of salami-slicing and redundancy, are particularly detrimental to the quality of systematic review and meta-analysis – which are considered the most rigorous in evidence hierarchy. Not only do they require more resources (e.g. time, effort) to screen for duplicates, but they also facilitate “cherry-picking” outcome report, which refers to the practice of selecting favorable information among multiple publications of a trial to manipulate the results. The extent and impact of salami-slicing and redundancy on IMIDs evidence remains poorly investigated and understood.
Therefore, this thesis aims to: describe the characteristics of secondary publications of RCTs evaluating the efficacy of systemic treatments in IMIDs (focused on psoriasis) and identify the associated factors with secondary publishing, outcome reporting and statistically significant findings in secondary publications. Furthermore, we aim to assess the impact of secondary publications on systematic reviews and meta-analyses of IMIDs.
Evaluation of Therapies for Advanced Cutaneous Squamous Cell Carcinoma Using French National Health Insurance Data
PhD candidate in Public Health
Supervisor: Emilie Sbidian, Olivier Dereure
Funding: Montpellier University
Doctoral thesis
Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer, responsible for approximately 20% of skin cancer-related deaths, with incidence rising due to population aging. While prognosis is generally favorable, advanced cSCC (acSCC) occurs mainly in frail, elderly patients and includes unresectable, radioresistant, or metastatic disease.
Until recently, only off-label anti-EGFR therapies (mainly cetuximab ± chemotherapy) were available in France, with limited efficacy and significant toxicity. Anti-PD-1 agents have since shown durable benefit with acceptable safety; cemiplimab is approved in Europe but, in France, reimbursed only after chemotherapy failure or contraindication.
Using the French National Health Data System (SNDS), our first study compares survival in patients receiving first-line anti-PD-1 versus cetuximab ± chemotherapy. Our second study will combine the SNDS and the WHO global pharmacovigilance database to characterize severe immune-related adverse events (irAEs) linked to anti-PD-1 therapy in acSCC. The third study will assess the impact of corticosteroids and other concomitant drugs on anti-PD-1 efficacy, given emerging evidence from other cancers. Collectively, these studies aim to optimize real-world therapeutic strategies and safety in acSCC management.
PhD candidate in Public Health
Supervisor: Emilie Sbidian, Laura Pina-Vegas
Doctoral thesis
Systemic lupus erythematosus (SLE) is a rare chronic autoimmune disease, mainly affecting women between 15 and 45 years. It involves multiple organs and follows a relapsing-remitting course, with manifestations ranging from cutaneous and rheumatologic symptoms to severe renal, neurological, or cardiorespiratory complications. Standard therapy combines hydroxychloroquine, glucocorticoids, and immunosuppressive agents. Complementing these treatments, two biologics, belimumab (anti-B cell activating factor) and anifrolumab (anti-type I interferon receptor), have been approved to reduce disease activity and flares while allowing corticosteroid tapering. However, their comparative effectiveness and long-term safety remain poorly documented, with reported risks including herpes zoster, psychiatric disorders, and rare cases of progressive multifocal leukoencephalopathy.
This thesis aims to evaluate and compare the real-world effectiveness of belimumab and anifrolumab using a target trial emulation in the French National Health Database (Système National des Données de Santé, SNDS) and to assess their safety profile by quantifying severe adverse events. A preliminary step involves validating an algorithm to identify SLE cases in the SNDS using hospital records from the Greater Paris University Hospitals (AP-HP) clinical data warehouse.
Enrollment 2023
Investigating the Dynamics of COVID-19 Transmission and Vaccination Behaviour: A Multi-Study Approach
PhD candidate in Public Health
Supervisor: Patrick Maison, Nadine Saleh
Funding: Public Health Ministry of Lebanon
Doctoral thesis
The COVID-19 pandemic has led to a global health crisis that has affected the lives of millions of people. By investigating the dynamics of the COVID 19 transmission, the vaccine effectiveness during different waves and the changes in the knowledge, attitude and practice related to vaccination post covid 19 we will understand the impact of the pandemic and the changes in people behaviour related to vaccine preventable diseases.
The aim of this proposed doctoral thesis is to investigate the dynamics of COVID-19 transmission and vaccination behavior.
Influenza vaccine: evaluation of interventions, burden and impact of prevention
PhD candidate in Public Health
Supervisor: Patrick Maison
Funding: Public Health Ministry of Lebanon
Doctoral thesis
According to the World Health Organization (WHO), seasonal influenza epidemics cause annually around 3 to 5 million cases of severe illness and around 290 000 to 650 000 respiratory deaths mainly among high-risk groups like older adults and children. Vaccination remains the most important intervention for influenza prevention. The Strategic Advisory Group of Experts on Immunization (SAGE) recommends influenza vaccination to certain high-risk groups to be administered each year to reduce the risk of serious complications.
It is critical to estimate the burden of disease to better understand its impact in addition to estimate the burden averted through vaccination mainly among high-risk groups.
On the other hand, vaccine hesitancy is a global concern with different reasons lying behind the refusal of the vaccine in different settings. Several interventions targeting different populations have been developed to increase influenza vaccination uptake. In this context, it is important to identify predictors and barriers of influenza vaccine uptake, to understand the impact of previous sensitization to routine influenza vaccination on acceptability of pandemic vaccination and to identify the most effective interventions in order to develop tailored ones that aim to enhance acceptance of the vaccine among target groups.
Stress, work-related burden, and immune-mediated inflammatory skin diseases
PhD candidate in Public Health
Supervisor: Khaled Ezzedine, Alexis Descatha
Funding: UPEC
Doctoral thesis
Although immune-mediated inflammatory skin diseases are different in clinical expression, they share common pathophysiological mechanisms involving lymphocyte activation. Indeed, in vivo studies involving animal models and human population studies have shown the important role of stress in modulating the immune response through the nervous and endocrine systems. Specifically, the interaction between the activated neuroendocrine system and the immune response is thought to contribute to the development and exacerbation of immune-mediated inflammatory diseases through the secretion of inflammatory cytokines. Work-related stress has been associated with an increased risk of chronic disease severity, particularly cardiovascular disease. Few data are available on skin pathologies.
Furthermore, rotating night work is known to have a negative impact on circadian rhythms. It is considered an emerging risk factor for multiple chronic diseases and increased inflammation probably due to stress caused by circadian disruption.
In particular, stress from night work appears to reduce the ability to repair oxidative DNA damage due to melatonin suppression. Previous studies have further reported epigenetic alterations in individuals who work night shifts, suggesting the potential for trans-generational impacts. In addition, stress caused by circadian rhythm changes during night work could potentially induce an increase in immunoglobulin E (IgE), suggesting increased inflammation and an increased imbalance of the T-helper 1 (Th1)/T-helper 2 (Th2) axis thereby increasing the risk of development and exacerbation of atopic diseases.
In the CONSTANCES cohort, a large French national cohort (https://www.constances.fr/), a specific questionnaire on skin diseases was sent to the study volunteers with a response rate of more than 70%. This survey included validated self-questionnaires for the self-diagnosis of the 5 chronic immune-mediated inflammatory diseases which allowed the identification of patients with a chronic dermatological disease, whether active at the time the questionnaire was sent or in remission. In addition, a self-assessment of the severity of these diseases was also reported by patients who responded positively to a diagnosis of chronic skin disease. The severity of inflammatory dermatoses will also be assessed by the prescription of systemic treatments related to these inflammatory dermatoses.
In addition, participants in the CONSTANCES cohort were asked to answer the following question: ‘Do you experience stressful situations in your relations with the public at work?’ with 4 possible levels of answers: (1) never or almost never, (2) rarely, (3) often, and (4) always or almost always, as well as the effort-reward balance. Furthermore, as part of the self-administered inclusion questionnaire, CONSTANCES cohort participants provide detailed retrospective information about each job they have held (starting with the first job up to the actual job at the time of the interview) and about any career breaks (lasting 6 months or more).
Information on jobs includes start and end dates, type of contract, working hours, and an open-ended question for more details on the occupation. Similarly, if there was an interruption, participants were asked to specify the time (start and end) and provide information on the reasons for the interruption (e.g., health, unemployment). These data provide a detailed description of the entire employment history for each individual in terms of an annual description of the employment situation between the ages of 25 and 45 (employment sequence), thus covering up to 21 years of career. Based on individual employment sequences, participants in the CONSTANCES cohort were classified into the following six career characteristics: (i) number of temporary contract jobs and (ii) ‘precarious careers’ classified by the number of job changes (iii) number of unemployment spells (iv) ‘involuntary interruptions’ according to the number of years out of work, (v) occupational category between the ages of 25 and 45, and (vi) ‘cumulative disadvantages’ the lack of promotion within the position held.
Finally, during the inclusion questionnaire, participants were asked about cumulative exposure to long work hours (≥ 10 hours per day for at least 50 days, yes/no) and the number of years of exposure (<1 year, short [1- <10 years], and long duration [≥ 10 years]).
The objectives of the thesis will be to:
- Evaluate the impact of stressful situations in the relations with the public at work on the severity of immune-mediated inflammatory dermatoses: vitiligo, psoriasis, atopic dermatitis, alopecia and hidradenitis suppurativa.
- Evaluate the impact of cumulative exposure to long working hours on the severity of immune-mediated inflammatory dermatoses: vitiligo, psoriasis, atopic dermatitis, peladerma and hidradenitis suppurativa.
- Study the impact of work loss on the severity of immune-mediated inflammatory dermatoses: vitiligo, psoriasis, atopic dermatitis, alopecia and hidradenitis suppurativa.
Efficacy and safety of biologic treatments in psoriasis: causal inference in observational data
PhD candidate in Public Health
Supervisor: Emilie Sbidian, Thang Vo
Funding: UPEC
Doctoral thesis
Biologic therapies have transformed psoriasis care, offering effective and well-tolerated options for this chronic, painful skin disease. However, they may increase the risk of inpatient-managed infections requiring hospitalization. For high-risk patients, such as those with recent infections, safety evidence is limited, and outpatient-managed infections are rarely studied alongside inpatient-managed infections. Besides, biologic persistence often declines over time, especially for TNF-inhibitors (infliximab, etanercept, adalimumab, certolizumab), partly due to antidrug antibody (ADAb) development. In rheumatoid arthritis, low-dose methotrexate with TNF-i reduces ADAs, but evidence in psoriasis is limited, and its role in persistence differences is unclear.
This 3-year PhD will use French National Health Insurance System (SNDS) data to:
- Assess the risk of inpatient-managed infection and outpatient-managed infection among biologic-new users with a history of infection.
- Evaluate the role of concomitant methotrexate in improving biologic persistence, and develop and apply novel methods for robust assessment in psoriasis drug evaluation using instrumental variable difference-in-difference (IV-DID) approach.
Dietary circadian rhythms -determinants, and link to metabolic health and inflammatory dermatoses
PhD candidate in Public Health
Supervisor: Khaled Ezzedine, Bernard Srour
Funding: ANR
Doctoral thesis
The impact of the nutritional quality of food intake on health is increasingly well known(1). However, the impact of the rhythm and timing of food intake has been little studied. Yet mounting evidence suggests that alterations in circadian rhythms due to certain irregularly-scheduled behaviors, characteristic of modern Western society, may play an important role in increasing the burden of non-communicable diseases.
As an example, night-shift work has been classified as probably carcinogenic to humans by the International Agency for Research on Cancer (2), and has been associated with an increased risk of several diseases, including psoriasis in women (3). In addition to exposure to light, which acts on the central clock, food intake is the main resynchronizing factor (zeitgebers) for peripheral clocks, especially in the liver (4).
More generally, the rhythmicity of eating habits (meal times and frequencies), over and above the quality of the diet itself, varies through the different stages of life (childhood, student youth, working youth, mid-life, retirement), and through the seasons or social activities (days worked, weekends, vacations, travel and time shifts). These circadian variations and disturbances are influenced by society and working life. In addition, the media, social networks and various commercial initiatives have, without scientific proof of efficacy, sparked an explosion of interest among the general public and patients in intermittent fasting (in particular time-limited eating), promoted to improve metabolic health and limit overweight. Experimental studies show that mice fed only during their active phase were protected against obesity, hyperinsulinemia and inflammation, compared to others consuming the same calories extended over 24 hours(5). Despite the results of these experimental studies, fundamental questions about the risk of non-communicable diseases remain unanswered in humans, and the optimal timing and frequency of daily meals and fasting for metabolic health are unknown.
The scientific and medical community is paying increasing attention to the role of these behaviours or diets in metabolic health and inflammatory dermatoses (6,7), given the strong mechanistic plausibility of these links, and the suggested links between mealtimes and gut microbiota composition(8). However, large-scale epidemiological studies exploring the association between time-restricted feeding, distinguishing between early time-restricted feeding (eTRE) and late time-restricted feeding (lTRE), are virtually non-existent, partly because the collection of such data requires detailed repeated dietary questionnaires including meal times, unavailable in most studies worldwide. The thesis hypothesis is that, beyond nutritional quality, there are optimal times and durations of food intake that can improve health and help prevent chronic disease. Individuals with behaviors close to this optimum would have more favorable metabolic, inflammatory and oxidative profiles, and a lower risk of chronic disease. In addition to changes in dietary quality, key stages of life would be accompanied by dietary rhythms that move away from or closer to these optimums.