Psychometric Properties and Domains Covered by Patient-Reported Outcome Measures Used in Trials Assessing Interventions for Chronic Pain.

OBJECTIVE: To identify the patient reported outcome measures (PROMs) used in clinical trials assessing interventions for chronic pain, describe their psychometric properties and the clinical domains they cover. STUDY DESIGN AND SETTING: We identified phase 3 or 4 interventional trials on adult participants (age >18) registered in clinicaltrials.gov between January 1, 2021 to December 31, 2022 and which provided "chronic pain" as a keyword condition. We excluded diagnostic studies and phase 1 or 2 trials. In each trial, one reviewer extracted all outcomes registered and identified those captured using PROMs. For each PROM used in more than 1% of identified trials, two reviewers assessed whether it covered the six important clinical domains from the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT): pain, emotional functioning, physical functioning, Participant ratings of global improvement of global improvement, symptoms and adverse events, and participant disposition (e.g., adherence to medication). Second, reviewers searched PubMed for both the initial publication and latest review reporting the psychometric properties of each PROM and their content validity, structural validity, internal consistency, reliability, measurement error, hypotheses testing, criterion validity and responsiveness using published criteria from the literature. RESULTS: In total, 596 trials assessing 4843 outcomes were included in the study (median sample size 60, interquartile range 40 to 100). Trials evaluated behavioral (22%), device-based (21%) and drug-based (10%) interventions. Of 495 unique PROMs, 55 were used in more than 1% trials (16 were generic pain measures; 8 were pain measures for specific diseases; 30 were measures of other symptoms or consequences of pain). About 50% PROMs had more than 50% of psychometric properties rated as sufficient. Scales often focused on a single clinical domain. Only 25% trials measured at least three clinical domains from IMMPACT. CONCLUSION: Only half of PROMs used in trials for chronic pain had sufficient psychometric properties for more than 50% of criteria assessed. Few PROMs assess more than one important clinical domain. Only 25% of trials measure more than 3/6 clinical domains considered important by IMMPACT.

Personalizing renal replacement therapy initiation in the intensive care unit: a reinforcement learning-based strategy with external validation on the AKIKI randomized controlled trials.

OBJECTIVE: The timely initiation of renal replacement therapy (RRT) for acute kidney injury (AKI) requires sequential decision-making tailored to individuals' evolving characteristics. To learn and validate optimal strategies for RRT initiation, we used reinforcement learning on clinical data from routine care and randomized controlled trials. MATERIALS AND METHODS: We used the MIMIC-III database for development and AKIKI trials for validation. Participants were adult ICU patients with severe AKI receiving mechanical ventilation or catecholamine infusion. We used a doubly robust estimator to learn when to start RRT after the occurrence of severe AKI for three days in a row. We developed a "crude strategy" maximizing the population-level hospital-free days at day 60 (HFD60) and a "stringent strategy" recommending RRT when there is significant evidence of benefit for an individual. For validation, we evaluated the causal effects of implementing our learned strategies versus following current best practices on HFD60. RESULTS: We included 3748 patients in the development set and 1068 in the validation set. Through external validation, the crude and stringent strategies yielded an average difference of 13.7 [95% CI -5.3 to 35.7] and 14.9 [95% CI -3.2 to 39.2] HFD60, respectively, compared to current best practices. The stringent strategy led to initiating RRT within 3 days in 14% of patients versus 38% under best practices. DISCUSSION: Implementing our strategies could improve the average number of days that ICU patients spend alive and outside the hospital while sparing RRT for many. CONCLUSION: We developed and validated a practical and interpretable dynamic decision support system for RRT initiation in the ICU.

Spread of awareness of COVID-19 between December 2019 and March 2020 in France.

During the early phase of outbreaks, awareness of the presence of the disease plays an important role in transmission dynamics. To investigate the processes of how people become aware of a disease, we conducted two complementary investigations. First, we surveyed 868 academic researchers in France, on the time and circumstances when they became aware of COVID-19 as an important event. We found that 25% did so before February 18th (first death in France), 50% did so before March 10th (first presidential allocution) and 75% did so before March 16th (announcement of the lockdown). Awareness came from nine categories of circumstances: (1) decisions taken by the government (elicited by 35.7% participants); (2) information from media or social media (24.7%); (3) conversation with friends (22.4%); (4) observed changes in their personal lives (14.0%); (5) decisions taken by the employer (9.2%); (6) observed changes at work (9.9%); (7) suspected case of COVID-19 in their entourage (3.1%); (8) fear for oneself or their entourage (2.8%) and (9) self-appraisal of scientific reports (2.8%). Second, we appraised three general media in France (a television news show, a radio news show, and a newspaper) and showed that COVID-19 became a preeminent topic only after March 1st 2020 when the epidemic is present on national soil. Our results show that multiple intricated factors prompt the awareness of an emerging infectious disease. Awareness is not solely driven by general media as they begin to focus on the topic late.

Heterogeneity of outcome measures in depression trials and the relevance of the content of outcome measures to patients: a systematic review.

Research waste occurs when randomised controlled trial (RCT) outcomes are heterogeneous or overlook domains that matter to patients (eg, relating to symptoms or functions). In this systematic review, we reviewed the outcome measures used in 450 RCTs of adult unipolar and bipolar depression registered between 2018 and 2022 and identified 388 different measures. 40% of the RCTs used the same measure (Hamilton Depression Rating Scale [HAMD]). Patients and clinicians matched each item within the 25 most frequently used measures with 80 previously identified domains of depression that matter to patients. Seven (9%) domains were not covered by the 25 most frequently used outcome measures (eg, mental pain and irritability). The HAMD covered a maximum of 47 (59%) of the 80 domains that matter to patients. An interim solution to facilitate evidence synthesis before a core outcome set is developed would be to use the most common measures and choose complementary scales to optimise domain coverage. TRANSLATIONS: For the French and Dutch translations of the abstract see Supplementary Materials section.

Stigma in vitiligo: associated factors and severity strata of the Patient Unique Stigmatization Holistic tool in Dermatology (PUSH-D) score.

BACKGROUND: Vitiligo is the most common cause of skin depigmentation worldwide. Patients with vitiligo may experience stigma and this needs to be addressed. OBJECTIVES: To evaluate stigma in patients with vitiligo, search for associated factors and establish severity strata for the Patient Unique Stigmatization Holistic tool in Dermatology (PUSH-D) for patients with vitiligo. METHODS: We conducted a cross-sectional study in ComPaRe Vitiligo, an e-cohort of adult patients with vitiligo. Stigmatization was assessed using the PUSH-D, a recently validated dermatology-specific stigmatization assessment tool. We conducted univariate and multivariable linear regression to identify patient and disease factors associated with the stigmatization. We used an anchor-based approach to define severity strata for the PUSH-D. RESULTS: In total, 318 patients participated (mean age 49.7 years; 73.9% women). Fitzpatrick skin phototype IV-VI, severe facial involvement (high Self-Assessment Vitiligo Extent Score of the face) and depression (high Patient Health Questionnaire-9 score) were positively -associated with a higher stigmatization score, although this association was weak [r = 0.24 (P < 0.001) and r = 0.30 (P < 0.001), respectively]. PUSH-D cutoff values that best discriminated patients with high and low stigma, as defined by the anchor question, were 13 and 23 (κ = 0.622, 95% confidence interval 0.53-0.71). CONCLUSIONS: Our study is the first to use a skin-specific stigmatization tool to assess stigma in patients with vitiligo. Creating strata helps to better interpret the PUSH-D in daily practice and may facilitate its use in clinical trials.

Vitiligo is an acquired autoimmune condition characterized by well-defined depigmented patches of skin on the body. The condition affects approximately 1% of the world's population and those living with vitiligo have long experienced stigmatization. Despite the fact that previous research has investigated the correlation between stigma and vitiligo using non-specific stigma tools, to our knowledge, no study has specifically assessed stigma in people with vitiligo. This study was carried out among French patients with vitiligo to evaluate both felt and actual stigma using the Patient Unique Stigmatization Holistic tool in Dermatology (PUSH-D), a new skin-specific stigma score. We also looked for correlations between PUSH-D scores and other questionnaires measuring levels of anxiety (GAD-7) and depression (PHQ-9). We found that PHQ-9 scores for depression were significantly positively correlated with PUSH-D scores, although these correlations were weak. When examining which factors were associated with higher stigma, we found that darker skin phototypes and severe facial involvement predicted higher stigma. However, we found that hand involvement did not. Overall, vitiligo is associated with a lot of stigma and it has been shown to be a barrier to employment. Therefore, an objective evaluation of vitiligo is required in order to facilitate access and reimbursement of treatment (including those existing and under development). The findings from this study highlight how further research is needed with more diverse groups of people, to better objectify stigma associated with vitiligo.

A core outcome domain set to assess cutaneous neurofibromas related to neurofibromatosis type 1 in clinical trials.

BACKGROUND: Cutaneous neurofibromas (cNF) are considered one of the highest burdens of neurofibromatosis type 1 (NF1). To date, no medical treatment can cure cNF or prevent their development. In that context, there is an urgent need to prepare and standardize the methodology of future trials targeting cNF. OBJECTIVES: The objective was to develop a core outcome domain set suitable for all clinical trials targeting NF1-associated cNF. METHODS: The validated approach of this work consisted of a three-phase methodology: (i) generating the domains [systematic literature review (SLR) and qualitative studies]; (ii) agreeing (three-round international e-Delphi consensus process and working groups); and (iii) voting. RESULTS: (i) The SLR and the qualitative studies (three types of focus groups and a French e-survey with 234 participants) resulted in a preliminary list of 31 candidate items and their corresponding definitions. (ii) A total of 229 individuals from 29 countries participated in the first round of the e-Delphi process: 71 patients, relatives or representatives (31.0%), 130 healthcare professionals (HCPs, 56.8%) and 28 researchers, representatives of a drug regulatory authority, industry or pharmaceutical company representatives or journal editors (12.2%). The overall participation rate was 74%. After round 2, five candidate items were excluded. Between rounds 2 and 3, international workshops were held to better understand the disagreements among stakeholders. This phase led to the identification of 19 items as outcome subdomains. (iii) The items were fused to create four outcome domains ('clinical assessment', 'daily life impact', 'patient satisfaction' and 'perception of health') and prioritized. The seven items that did not reach consensus were marked for the research agenda. The final core outcome domain set reached 100% of the votes of the steering committee members. CONCLUSIONS: Although numerous outcomes can be explored in studies related to cNF in NF1, the present study offers four outcome domains that should be reported in all trial studies, agreed on by international patients, relatives and representatives of patients; HCPs; researchers, representatives of drug regulatory authorities or pharmaceutical companies and journal editors. The next step will include the development of a set of core outcome measurement instruments to further standardize how these outcomes should be assessed.

Impact of surgery after endoscopically resected high-risk T1 colorectal cancer: results of an emulated target trial.

BACKGROUND AND AIMS: We aimed to compare the long-term outcomes of patients with high-risk T1 colorectal cancer (CRC) resected endoscopically who received either additional surgery or surveillance. METHODS: We used data from routine care to emulate a target trial aimed at comparing 2 strategies after endoscopic resection of high-risk T1 CRC: surgery with lymph node dissection (treatment group) versus surveillance alone (control group). All patients from 14 tertiary centers who underwent an endoscopic resection for high-risk T1 CRC between March 2012 and August 2019 were included. The primary outcome was a composite outcome of cancer recurrence or death at 48 months. RESULTS: Of 197 patients included in the analysis, 107 were categorized in the treatment group and 90 were categorized in the control group. From baseline to 48 months, 4 of 107 patients (3.7%) died in the treatment group and 6 of 90 patients (6.7%) died in the control group. Four of 107 patients (3.7%) in the treatment group experienced a cancer recurrence and 4 of 90 patients (4.4%) in the control group experienced a cancer recurrence. After balancing the baseline covariates by inverse probability of treatment weighting, we found no significant difference in the rate of death and cancer recurrence between patients in the 2 groups (weighted hazard ratio, .95; 95% confidence interval, .52-1.75). CONCLUSIONS: Our study suggests that patients with high-risk T1 CRC initially treated with endoscopic resection may not benefit from additional surgery.

Assessment of US Food and Drug Administration-Approved Digital Medical Devices for Just-in-Time Interventions: A Systematic Review.

Importance: Just-in-time interventions (JITIs) are a type of digital therapeutic intervention that combines remote monitoring tools and algorithms to personalize the delivery of specific interventions at the right time. The US Food and Drug Administration (FDA) regulatory approval documents are often the only available source of information on the effectiveness of therapeutic interventions based on these devices. Objective: To systematically review the publicly available information from the FDA on all recently approved medical devices used in JITIs to (1) assess how they operate to deliver JITIs and (2) appraise the evidence supporting their performance and clinical effectiveness. Evidence Review: Two reviewers systematically searched the Premarket Notifications (510(k)), Premarket Approvals, De Novo, and Humanitarian Device Exemption databases from January 2019 to December 2021 for all entries associated with devices that monitored patients' data over time to personalize the delivery of interventions to treat, prevent, or mitigate health conditions or events. They assessed whether the product summaries (1) enabled an understanding of how the device operated to deliver a JITI (eg, the nature, type, and frequency of the monitoring, the nature of the decision algorithm, and the nature and intended receiver of the intervention); (2) informed about the performance and effectiveness of the JITI; and (3) included information on data security and ownership. Findings: In total, 38 devices were included in this review. These were mainly intended for cardiac conditions (12 [31.6%]), diabetes (10 [26.3%]), and neurological diseases (4 [10.5%]). Monitoring devices ranged from wearable (18 of 28 [64.4%]; eg, smartwatches) to implanted sensors (6 of 28 [21.4%]; eg, inserted electrocardiographic sensors). Only 10 of 38 product summaries (26.3%) allowed a full understanding of how the device operated to deliver a JITI. Similarly, only 12 of 28 (42.9%), 12 of 36 (33.3%), and 5 of 38 (13.2%) reported the assessment of the performance of the monitoring device, assessment of the decision algorithm, and results of clinical studies assessing the effectiveness of the JITI, respectively. Finally, 14 of 36 product summaries (38.9%) included some information on data security, but none included information on data ownership. Conclusion and Relevance: The results of this systematic review suggest that the information publicly available in the FDA databases on the performance and effectiveness of digital medical devices used in JITIs is heterogeneous.

A methodological framework allows the identification of personomic markers to consider when designing personalized interventions.

OBJECTIVES: To develop a methodological framework to identify and prioritize personomic markers (e.g., psychosocial situation, beliefs…) to consider for personalizing interventions and to test in smoking cessation interventions. STUDY DESIGN AND SETTING: (1) We identified potential personomic markers considered in protocols of personalized interventions, in reviews of predictors of smoking cessation, and in interviews with general practitioners. (2) Physicians, and patient smokers or former smokers selected the markers they considered most relevant during online paired comparison experiments. Data were analyzed with Bradley Terry Luce models. RESULTS: Thirty-six personomic markers were identified from research evidence. They were evaluated by 795 physicians (median age: 34, IQR [30-38]; 95% general practitioners) and 793 patients (median age: 54, IQR [42-64], 71.4% former smokers) during 11,963 paired comparisons. Physicians identified patients' motivation for quitting (e.g., Prochaska stages), patients' preferences, and patients' fears and beliefs (e.g., concerns about weight gain) as the most relevant elements to personalize smoking cessation. Patients considered their motivation for quitting, smoking behavior (e.g., smoking at home/at work), and tobacco dependence (e.g., Fagerström Test) as the most relevant elements to consider. CONCLUSION: We provide a methodological framework to prioritize which personomic markers should be considered when developing smoking cessation interventions.

cNF-Skindex in Adults Living with Neurofibromatosis 1: Severity Strata in France and Validation in United States Adults.

Cutaneous neurofibromas (cNF) contribute to the impairment of QOL in individuals with neurofibromatosis 1. The cNF-Skindex, validated in a French population, specifically assesses the cNF-related QOL. In this study, we first defined severity strata using an anchoring approach on the basis of patient's burden. In total, 209 patients answered the anchor question and the cNF-Skindex. We tested the agreement among the three strata, generated by all potential couples of cut-off values of the cNF-Skindex and the three strata defined in the anchor question. The cut-off values 12 and 49 provided the highest Kappa value (κ = 0.685, 95% confidence interval = 0.604-0.765). Second, we validated the score and the strata in a United States population using the answers provided by 220 French and 148 United States adults. In the multivariable linear regression analysis, the country of origin was not a factor associated with the score (P = 0.297). The number of cNF along the different severity strata was similar between the French and the United States populations. In conclusion, stratification constitutes a powerful tool to better interpret the cNF-Skindex in daily practice and in clinical trials. This study validates its use in two populations that together constitute a large cohort of patients willing to participate in clinical research.

Trajectories of the evolution of post-COVID-19 condition, up to two years after symptoms onset.

OBJECTIVES: We aimed to identify trajectories of the evolution of post-COVID-19 condition, up to 2 years after symptom onset. METHODS: The ComPaRe long COVID e-cohort is a prospective cohort of patients with symptoms lasting at least 2 months after SARS-CoV2 infection. We used trajectory modeling to identify different trajectories in the evolution of post-COVID-19 condition, based on symptoms collected every 60 days using the long COVID Symptom Tool. RESULTS: A total of 2197 patients were enrolled in the cohort between December 2020 and July 2022 when the Omicron variant was not dominant. Three trajectories of the evolution of post-COVID-19 condition were identified: "high persistent symptoms" (4%), "rapidly decreasing symptoms" (5%), and "slowly decreasing symptoms" (91%). Participants with highly persistent symptoms were older and more likely to report a history of systemic diseases. They often reported tachycardia, bradycardia, palpitations, and arrhythmia. Participants with rapidly decreasing symptoms were younger and more likely to report a confirmed infection. They often reported diarrhea and back pain. Participants with slowly decreasing symptoms were more likely to have a history of functional diseases. CONCLUSION: Most patients with post-COVID-19 condition improve slowly over time, while 5% have rapid improvement in the 2 years after symptom onset and 4% have a persistent condition.

Facial involvement is reflective of patients' global perception of vitiligo extent.

BACKGROUND: The involvement of visible areas in vitiligo has been found to be correlated with increased psychiatric morbidity. Although multiple tools have been developed to assess vitiligo, no cutoff for improvement or worsening of vitiligo from a patient's perspective has been established. OBJECTIVES: To determine the minimal clinically important difference (MCID) of the Self-Assessment Vitiligo Extent Score (SA-VES) in patients with vitiligo and to evaluate, from the patient's perspective, the importance of the change in the involvement of visible areas (face and hands) in patients' overall perception of disease worsening or improving. METHODS: This was a cross-sectional study in the context of the ComPaRe e-cohort. Adult patients with vitiligo were invited to answer online questionnaires. They completed the SA-VES twice, 1 year apart. In addition, patients answered a 5-point Likert anchor question aimed at assessing their perception of the evolution of the extent of their vitiligo. The MCID was calculated using distribution- and anchor-based approaches. Using ordinal logistic regression, the change of vitiliginous lesions on the face or hands was compared to the overall extent of vitiligo (patches on all body areas). RESULTS: In total, 244 patients with vitiligo were included in the analyses; 20 (8%) were found to have an improvement in their vitiligo. The MCID in worsened patients was equal to a 1.3% body surface area [95% confidence interval (CI) 1.01-1.43] increase in the SA-VES. For participants with improved vitiligo, the MCID was equal to a decrease in total SA-VES of 1.3% (95% CI 0.867-1.697). Patients' perceptions of change in their vitiligo was increased sevenfold when it affected the face vs. the rest of the body. CONCLUSIONS: Changes in the facial SA-VES were highly correlated with patients' impressions of the extent of vitiligo.

Efficacy of first dose of covid-19 vaccine versus no vaccination on symptoms of patients with long covid: target trial emulation based on ComPaRe e-cohort.

Objective: To evaluate the effect of covid-19 vaccination on the severity of symptoms in patients with long covid. Design: Target trial emulation based on ComPaRe e-cohort. Data source: ComPaRe long covid cohort, a nationwide e-cohort (ie, a cohort where recruitment and follow-up are performed online) of patients with long covid, in France. Methods: Adult patients (aged ≥18 years) enrolled in the ComPaRe cohort before 1 May 2021 were included in the study if they reported a confirmed or suspected SARS-CoV-2 infection, symptoms persistent for >3 weeks after onset, and at least one symptom attributable to long covid at baseline. Patients who received a first covid-19 vaccine injection were matched with an unvaccinated control group in a 1:1 ratio according to their propensity scores. Number of long covid symptoms, rate of complete remission of long covid, and proportion of patients reporting an unacceptable symptom state at 120 days were recorded. Results: 910 patients were included in the analyses (455 in the vaccinated group and 455 in the control group). By 120 days, vaccination had reduced the number of long covid symptoms (mean 13.0 (standard deviation 9.4) in the vaccinated group v 14.8 (9.8) in the control group; mean difference -1.8, 95% confidence interval -3.0 to -0.5) and doubled the rate of patients in remission (16.6% v 7.5%, hazard ratio 1.93, 95% confidence interval 1.18 to 3.14). Vaccination reduced the effect of long covid on patients' lives (mean score on the impact tool 24.3 (standard deviation 16.7) v 27.6 (16.7); mean difference -3.3, 95% confidence interval -5.7 to -1.0) and the proportion of patients with an unacceptable symptom state (38.9% v 46.4%, risk difference -7.4%, 95% confidence interval -14.5% to -0.3%). In the vaccinated group, two (0.4%) patients reported serious adverse events requiring admission to hospital. Conclusion: In this study, covid-19 vaccination reduced the severity of symptoms and the effect of long covid on patients' social, professional, and family lives at 120 days in those with persistent symptoms of infection.

Patients' Perspectives on How to Improve Endometriosis Care: A Large Qualitative Study Within the ComPaRe-Endometriosis e-Cohort.

Background: Endometriosis is a chronic gynecological condition that affects about 10% of women of reproductive age. Despite its prevalence, diagnosis is often delayed, misdiagnosis is common, and treatment options are poor. This study aimed at capturing ideas to improve endometriosis care from the patients' perspectives. Materials and Methods: We analyzed cross-sectional data from 1,000 adult patients in ComPaRe-Endometriosis (a French prospective e-cohort focused on endometriosis) who answered to the open-ended question: "If you had a magic wand, what would you change about your health care?". The free-text responses were analyzed by qualitative thematic analysis using an inductive approach. Results: Patients had a mean age of 34.1 years (standard deviation = 8.1); 56% and 42% had stage IV disease or deep endometriosis, respectively. They elicited 2,487 ideas to improve the management of endometriosis, which were categorized into 61 areas of improvement, further grouped into 14 themes. The top five areas of improvement were mentioned by >10% of the patients and were to (1) train caregivers to develop their knowledge on the disease, (2) provide better management of daily pain and pain attacks, (3) take patient-reported symptoms seriously, (4) standardize diagnostic processes to improve early detection, and (5) have caregivers listen more to the patients. Conclusions: We identified 61 areas for improvement in endometriosis care. These results reflect patients' expectations in terms of management of their disease and will be useful to design a better global care for endometriosis from the patients' perspectives.

A systematic scoping review of just-in-time, adaptive interventions finds limited automation and incomplete reporting.

OBJECTIVES: To describe the degree of automation in just-in-time, adaptive interventions (JITAIs) assessed in randomized controlled trials (RCTs) in any medical specialty, and to assess the completeness of intervention reporting. STUDY DESIGN AND SETTING: Systematic scoping review-we searched PubMed, PsycINFO, and Web of Science, from 1 January 2019 to 2 March 2021, for reports of RCTs assessing JITAIs. We assessed whether study reports included the minimum information required to replicate the interventions based on JITAI frameworks. We described JITAIs according to their automation level using an established framework (partially, highly, or fully automated), and care workload distribution (requiring work from patients, health care professionals [HCPs], both, or neither). RESULTS: We included 88 JITAIs (62%, n = 55 supported chronic illness management and 12%, n = 11 supported health behavior change). Overall, 77% (n = 68) of JITAIs were missing some information required to replicate the intervention (e.g., n = 38, 43% inadequately reported the algorithm used to select intervention components). Only fifteen (17%) JITAIs were fully automated and did not require additional work from HCPs nor patients. Of the remaining JITAIs, 36% required work from both patients and HCPs, and 47% required work from either patients or HCPs. CONCLUSION: Most JITAIs are not fully automated and require work from the HCPs and patients.

Important adverse events to be evaluated in antidepressant trials and meta-analyses in depression: a large international preference study including patients and healthcare professionals.

BACKGROUND: Non-serious adverse events (NSAEs) should be captured and reported because they can have a significant negative impact on patients and treatment adherence. However, the reporting of NSAEs in randomised controlled trials (RCTs) is limited. OBJECTIVE: To identify the most important NSAEs of antidepressants for patients and clinicians, to be evaluated in RCTs and meta-analyses. METHODS: We conducted online international surveys in English, German and French, including (1) adults prescribed an antidepressant for a depressive episode and (2) healthcare professionals (HCPs) prescribing antidepressants. Participants ranked the 30 most frequent NSAEs reported in the scientific literature. We fitted logit models for sets of ranked items and calculated for each AE the probability to be ranked higher than the least important AE. We also identified additional patient-important AEs not included in the ranking task via open-ended questions. FINDINGS: We included 1631 patients from 44 different countries (1290 (79.1%) women, mean age 39.4 (SD 13), 289 (37.1%) with severe depression (PHQ-9 score ≥20)) and 281 HCPs (224 (79.7%) psychiatrists). The most important NSAEs for patients were insomnia (95.9%, 95% CI 95.2% to 96.5%), anxiety (95.2%, 95% CI 94.3% to 95.9%) and fatigue (94.6%, 95% CI 93.6% to 95.4%). The most important NSAEs for HCPs were sexual dysfunction (99.2%, 95% CI 98.5% to 99.6%), weight gain (98.9%, 95% CI 97.7% to 99.4%) and erectile problems (98.8%, 95% CI 97.7% to 99.4%). Participants reported 66 additional NSAEs, including emotional numbing (8.6%), trouble with concentration (7.6%) and irritability (6%). CONCLUSIONS: These most important NSAEs should be systematically reported in antidepressant trials. CLINICAL IMPLICATIONS: The most important NSAEs should contribute to the core outcome set for harms in depression.

Course of post COVID-19 disease symptoms over time in the ComPaRe long COVID prospective e-cohort.

About 10% of people infected by severe acute respiratory syndrome coronavirus 2 experience post COVID-19 disease. We analysed data from 968 adult patients (5350 person-months) with a confirmed infection enroled in the ComPaRe long COVID cohort, a disease prevalent prospective e-cohort of such patients in France. Day-by-day prevalence of post COVID-19 symptoms was determined from patients' responses to the Long COVID Symptom Tool, a validated self-reported questionnaire assessing 53 symptoms. Among patients symptomatic after 2 months, 85% still reported symptoms one year after their symptom onset. Evolution of symptoms showed a decreasing prevalence over time for 27/53 symptoms (e.g., loss of taste/smell); a stable prevalence over time for 18/53 symptoms (e.g., dyspnoea), and an increasing prevalence over time for 8/53 symptoms (e.g., paraesthesia). The disease impact on patients' lives began increasing 6 months after onset. Our results are of importance to understand the natural history of post COVID-19 disease.

Patients' Perspectives on Transforming Clinical Trial Participation: Large Online Vignette-based Survey.

BACKGROUND: Patients' participation is crucial to the success of randomized controlled trials (RCTs). However, recruiting and retaining patients in trials remain a challenge. OBJECTIVE: This study aims to describe patients' preferences for the organization of RCTs (visits on- site or remotely) and evaluate the potential impact of fulfilling preferences on their willingness to participate in a clinical trial. METHODS: This was a vignette-based survey. Vignettes were case scenarios of real clinical trials assessing pharmacological treatments. These RCTs evaluated 6 prevalent chronic diseases (ie, osteoporosis, osteoarthritis, asthma, cardiovascular diseases, diabetes, and endometriosis). Each vignette described (1) the RCT and characteristics of the treatment tested (ie, doses, administration routes) and (2) the trial procedures and different options (on-site or remotely) for how the trial was organized for informed consent, follow-up visits, and communication of results when the trial was completed. We recruited 628 participants from ComPaRe (www.compare.aphp.fr), a French e-cohort of patients with chronic diseases. The outcomes were the participants' preferences for the way the trial was organized (on-site or remotely) and their willingness to participate in the trial. RESULTS: Of the 628 participants who answered the vignettes, 491 (78.2%) were female (median age 55 years), with different chronic diseases ranging from endometriosis in 59 of 491 (12%) patients to asthma in 133 of 628 (21.2%) patients. In addition, 38 (6.1%) participants wanted to provide informed consent and all trial visits on-site, 176 (28%) wished to participate in the trial entirely remotely, and 414 (65.9%) wanted to combine remote-based and hospital-based visits. Considering the trial as a whole, when the trial was organized in a way that the patients preferred, the median (Q1-Q3) likelihood of participation in the trial was 90% (80-100) versus 60% (30-80) if the trial followed the patients' nonpreferred model. Furthermore, 256 (40.8%) patients responded to open-ended questions expressing their experience with trial participation and visits to the hospital and providing suggestions for improvement. The patients emphasized the need to personalize the way a trial is organized according to each patient's needs and conditions. CONCLUSIONS: There was a significant diversity in the participants' preferences. Most participants preferred hybrid organization involving both on-site and remote visits. Participants were more likely to participate in a trial organized according to their preferences.