Sensitivity and Specificity of Using GPT-3.5 Turbo Models for Title and Abstract Screening in Systematic Reviews and Meta-analyses.

BACKGROUND: Systematic reviews are performed manually despite the exponential growth of scientific literature. OBJECTIVE: To investigate the sensitivity and specificity of GPT-3.5 Turbo, from OpenAI, as a single reviewer, for title and abstract screening in systematic reviews. DESIGN: Diagnostic test accuracy study. SETTING: Unannotated bibliographic databases from 5 systematic reviews representing 22 665 citations. PARTICIPANTS: None. MEASUREMENTS: A generic prompt framework to instruct GPT to perform title and abstract screening was designed. The output of the model was compared with decisions from authors under 2 rules. The first rule balanced sensitivity and specificity, for example, to act as a second reviewer. The second rule optimized sensitivity, for example, to reduce the number of citations to be manually screened. RESULTS: Under the balanced rule, sensitivities ranged from 81.1% to 96.5% and specificities ranged from 25.8% to 80.4%. Across all reviews, GPT identified 7 of 708 citations (1%) missed by humans that should have been included after full-text screening at the cost of 10 279 of 22 665 false-positive recommendations (45.3%) that would require reconciliation during the screening process. Under the sensitive rule, sensitivities ranged from 94.6% to 99.8% and specificities ranged from 2.2% to 46.6%. Limiting manual screening to citations not ruled out by GPT could reduce the number of citations to screen from 127 of 6334 (2%) to 1851 of 4077 (45.4%), at the cost of missing from 0 to 1 of 26 citations (3.8%) at the full-text level. LIMITATIONS: Time needed to fine-tune prompt. Retrospective nature of the study, convenient sample of 5 systematic reviews, and GPT performance sensitive to prompt development and time. CONCLUSION: The GPT-3.5 Turbo model may be used as a second reviewer for title and abstract screening, at the cost of additional work to reconcile added false positives. It also showed potential to reduce the number of citations before screening by humans, at the cost of missing some citations at the full-text level. PRIMARY FUNDING SOURCE: None.

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.

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.

Development and Validation of the Long Coronavirus Disease (COVID) Symptom and Impact Tools: A Set of Patient-Reported Instruments Constructed From Patients' Lived Experience.

BACKGROUND: To develop and validate patient-reported instruments, based on patients' lived experiences, for monitoring the symptoms and impact of long coronavirus disease (covid). METHODS: The long covid Symptom and Impact Tools (ST and IT) were constructed from the answers to a survey with open-ended questions to 492 patients with long COVID. Validation of the tools involved adult patients with suspected or confirmed coronavirus disease 2019 (COVID-19) and symptoms extending over 3 weeks after onset. Construct validity was assessed by examining the relations of the ST and IT scores with health-related quality of life (EQ-5D-5L), function (PCFS, post-COVID functional scale), and perceived health (MYMOP2, Measure yourself medical outcome profile 2). Reliability was determined by a test-retest. The "patient acceptable symptomatic state" (PASS) was determined by the percentile method. RESULTS: Validation involved 1022 participants (55% with confirmed COVID-19, 79% female, and 12.5% hospitalized for COVID-19). The long COVID ST and IT scores were strongly correlated with the EQ-5D-5L (rs = -0.45 and rs = -0.59, respectively), the PCFS (rs = -0.39 and rs = -0.55), and the MYMOP2 (rs = -0.40 and rs = -0.59). Reproducibility was excellent with an interclass correlation coefficient of 0.83 (95% confidence interval .80 to .86) for the ST score and 0.84 (.80 to .87) for the IT score. In total, 793 (77.5%) patients reported an unacceptable symptomatic state, thereby setting the PASS for the long covid IT score at 30 (28 to 33). CONCLUSIONS: The long covid ST and IT tools, constructed from patients' lived experiences, provide the first validated and reliable instruments for monitoring the symptoms and impact of long covid.

Important Issues to Severe Trauma Survivors: A Qualitative Study.

OBJECTIVE: Identify issues that are important to severe trauma survivors up to 3 years after the trauma. BACKGROUND: Severe trauma is the first cause of disability-adjusted life years worldwide, yet most attention has focused on acute care and the impact on long-term health is poorly evaluated. METHOD: We conducted a large-scale qualitative study based on semi-structured phone interviews. Qualitative research methods involve the systematic collection, organization, and interpretation of conversations or textual data with patients to explore the meaning of a phenomenon experienced by individuals themselves. We randomly selected severe trauma survivors (abbreviated injury score ≥3 in at least 1 body region) who were receiving care in 6 urban academic level-I trauma centers in France between March 2015 and March 2018. We conducted double independent thematic analysis. Issues reported by patients were grouped into overarching domains by a panel of 5 experts in trauma care. Point of data saturation was estimated with a mathematical model. RESULTS: We included 340 participants from 3 months to 3 years after the trauma [median age: 41 years (Q1-Q3 24-54), median injury severity score: 17 (Q1-Q3 11-22)]. We identified 97 common issues that we grouped into 5 overarching domains: body and neurological issues (29 issues elicited by 277 participants), biographical disruption (23 issues, 210 participants), psychological and personality issues (21 issues, 147 participants), burden of treatment (14 issues, 145 participants), and altered relationships (10 issues, 87 participants). Time elapsed because the trauma, injury location, or in-hospital trauma severity did not affect the distribution of these domains across participants' answers. CONCLUSIONS: This qualitative study explored trauma survivors' experiences of the long-term effect of their injury and allowed for identifying a set of issues that they consider important, including dimensions that seem overlooked in trauma research. Our findings confirm that trauma is a chronic medical condition that demands new approaches to post-discharge and long-term care.

Belief and adherence to COVID 19-lockdown restrictions in patients with asthma versus other chronic diseases: results from a cross-sectional survey nested in the ComPaRe e-cohort, in France.

BACKGROUND: Asthma patients are under-represented among patients with COVID-19. Their behavior during lockdown and associated restrictions is unknown, as well as whether it was influenced by coexistent cardiovascular conditions. METHODS: We conducted a cross-sectional survey in May 2020, in France, nested in ComPaRe, an e-cohort of adults with chronic diseases. A self-administered questionnaire was mailed to 10,859 people; 3701 fully completed questionnaires. The prevalence of self-reported asthma was 7%. Patients were classified in 4 categories: asthma with (n = 106) or without (n = 149) cardiovascular disease and other diseases with (n = 1186) or without (n = 2260) cardiovascular disease. RESULT: Adherence to movement restrictions during the lockdown was very strong: 89% of participants reported a frequency of outings of "less than once per week" and "once or twice per week" for errands and no family-related outings during the lockdown. This proportion and frequency of outings were similar whatever the chronic disease (p = 0.122). Most patients (96%) reported a high feeling of security during the lockdown, but 95% felt anxious or depressed, with no difference by disease. As compared with patients with controlled asthma, those with uncontrolled asthma more frequently reported complaints related to deteriorated medical follow-up, waived care, anxiety or depression. CONCLUSIONS: Behaviors during the lockdown in France among the asthma population did not differ from patients with other chronic diseases in this cohort, which strengthens hypotheses for specific disease-related susceptibility to explain the low representation of asthmatics among COVID-19 cases. Special attention should be paid to the subgroup of patients with uncontrolled asthma during lockdowns.

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.

Baseline Characteristics of a National French E-Cohort of Hidradenitis Suppurativa in ComPaRe and Comparison with Other Large Hidradenitis Suppurativa Cohorts.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition substantially impacting patients' quality of life; the pathogenesis remains unclear, and treatment is complex and not yet standardized. Observational data are increasingly being used to evaluate therapeutics in "real-life" interventions, and the development of e-cohorts is offering new tools for epidemiological studies at the population level. OBJECTIVE: The aim of this study was to describe the clinical characteristics and treatment history of HS participants in the Community of Patients for Research (ComPaRe) cohort and to compare these to other cohorts. METHODS: We performed a cross-sectional study of the baseline data of HS participants in ComPaRe, an e-cohort of patients with chronic diseases. Data were collected using patient-reported questionnaires about clinical-dem-ographic aspects, quality of life, and treatment history. RESULTS: A total of 396 participants (339 females, 57 males) were included (mean age 38 years); 83 (21%) had a family history of HS, 227 (57.3%) were current smokers, and 241 (60.9%) were overweight or obese. Most of the participants declared a Hurley stage II (n = 263, 66.4%) or III (n = 76, 20.3%). The breast was more frequently affected in women than men (37.5 vs. 5.3%, p < 0.0001), whereas the dorsal region was more frequently affected in men (39.5 vs. 10.9%, p < 0.0001). Increased disease stage was associated with obesity (25.9 vs. 33.8 vs. 51.3%, p = 0.02) and some HS localizations (genital [p < 0.005], pubis [p < 0.007], gluteal fold [p = 0.02], and groin [p < 0.0001]). The most frequently prescribed treatments were oral antibiotics (n = 362, 91.4%), especially amoxicillin-clavulanic acid and cyclins. Less than 10% of participants received biologics. Most of these results were consistent with previously published cohorts. CONCLUSION: Recruitment of participants by such a web platform can be a faster way to get relevant scientific data for a wide variety of patients that could be used for epidemiological studies and to evaluate therapeutics in "real-life" interventions.

Methods to Generate Innovative Research Ideas and Improve Patient and Public Involvement in Modern Epidemiological Research: Review, Patient Viewpoint, and Guidelines for Implementation of a Digital Cohort Study.

BACKGROUND: Patient and public involvement (PPI) in research aims to increase the quality and relevance of research by incorporating the perspective of those ultimately affected by the research. Despite these potential benefits, PPI is rarely included in epidemiology protocols. OBJECTIVE: The aim of this study is to provide an overview of methods used for PPI and offer practical recommendations for its efficient implementation in epidemiological research. METHODS: We conducted a review on PPI methods. We mirrored it with a patient advocate's viewpoint about PPI. We then identified key steps to optimize PPI in epidemiological research based on our review and the viewpoint of the patient advocate, taking into account the identification of barriers to, and facilitators of, PPI. From these, we provided practical recommendations to launch a patient-centered cohort study. We used the implementation of a new digital cohort study as an exemplary use case. RESULTS: We analyzed data from 97 studies, of which 58 (60%) were performed in the United Kingdom. The most common methods were workshops (47/97, 48%); surveys (33/97, 34%); meetings, events, or conferences (28/97, 29%); focus groups (25/97, 26%); interviews (23/97, 24%); consensus techniques (8/97, 8%); James Lind Alliance consensus technique (7/97, 7%); social media analysis (6/97, 6%); and experience-based co-design (3/97, 3%). The viewpoint of a patient advocate showed a strong interest in participating in research. The most usual PPI modalities were research ideas (60/97, 62%), co-design (42/97, 43%), defining priorities (31/97, 32%), and participation in data analysis (25/97, 26%). We identified 9 general recommendations and 32 key PPI-related steps that can serve as guidelines to increase the relevance of epidemiological studies. CONCLUSIONS: PPI is a project within a project that contributes to improving knowledge and increasing the relevance of research. PPI methods are mainly used for idea generation. On the basis of our review and case study, we recommend that PPI be included at an early stage and throughout the research cycle and that methods be combined for generation of new ideas. For e-cohorts, the use of digital tools is essential to scale up PPI. We encourage investigators to rely on our practical recommendations to extend PPI in future epidemiological studies.

Impact of an interactive web tool on patients' intention to receive COVID-19 vaccination: a before-and-after impact study among patients with chronic conditions in France.

OBJECTIVES: In France, about 30% of the population refuses COVID-19 vaccination outright, and 9 to 40% are hesitant. We developed and evaluated an interactive web tool providing transparent and reliable information on the benefits and risks of COVID-19 vaccination. METHODS: The most recent scientific data at the time of the study were implemented into an interactive web tool offering individualized information on the risks of COVID-19 infection-related events versus vaccination-related serious adverse events. The tool was evaluated during a before-and-after impact study nested in ComPaRe, a French e-cohort of adult patients with chronic conditions. Primary outcome was the proportion of patients intending to receive vaccination after using the tool, among those not intending to receive it at baseline. RESULTS: Between January 8 and 14, 2021, we enrolled 3152 patients in the study [mean age 55.2 (SD: 16.9), 52.9% women and 63% with ≥ 2 chronic conditions]. Before consulting the tool, 961 (30.5%) refused to be vaccinated until further data on efficacy/safety was obtained and 239 (7.5%) outright refused vaccination. Among these 1200 patients, 96 (8.0%, number needed to treat: 12.5) changed their mind after consulting the tool and would subsequently accept vaccination. CONCLUSIONS: Our interactive web tool represents a scalable method to help increase the intent to receive COVID-19 vaccination among patients with chronic conditions and address vaccine hesitancy. Since April 2021, our tool has been embedded on the official webpage of the French Government for COVID-19 information.

Use of wearable biometric monitoring devices to measure outcomes in randomized clinical trials: a methodological systematic review.

BACKGROUND: Wearable biometric monitoring devices (BMDs) have the potential to transform the conduct of randomized controlled trials (RCTs) by shifting the collection of outcome data from single measurements at predefined time points to dense continuous measurements. METHODS: Methodological systematic review to understand how recent RCTs used BMDs to measure outcomes and to describe the reporting of these RCTs. Electronic search was performed in the Cochrane Central Register of Controlled Trials, PubMed, and EMBASE and completed a page-by-page hand search in five leading medical journals between January 1, 2018, and December 31, 2018. Three reviewers independently extracted all primary and secondary outcomes collected using BMDs, and assessed (1) the definitions used to summarize BMD outcome data; (2) whether the validity, reliability, and responsiveness of sensors was reported; (3) the discrepancy with outcomes prespecified in public clinical trial registries; and (4) the methods used to manage missing and incomplete BMD outcome data. RESULTS: Of the 4562 records screened, 75 RCTs were eligible. Among them, 24% tested a pharmacological intervention and 57% used an inertial measurement sensor to measure physical activity. Included trials involved 464 outcomes (average of 6 [SD = 8] outcomes per trial). In total, 35 trials used a BMD to measure a primary outcome. Several issues affected the value and transparency of trials using BMDs to measure outcomes. First, the definition of outcomes used in the trials was highly heterogeneous (e.g., 21 diabetes trials had 266 outcomes and 153 had different unique definitions to measure diabetes control), which limited the combination and comparison of results. Second, information on the validity, reliability, and responsiveness of sensors used was lacking in 74% of trials. Third, half (53%) of the outcomes measured with BMDs had not been prespecified, with a high risk of outcome reporting bias. Finally, reporting on the management of incomplete outcome data (e.g., due to suboptimal compliance with the BMD) was absent in 68% of RCTs. CONCLUSIONS: Use of BMDs to measure outcomes is becoming the norm rather than the exception in many fields. Yet, trialists need to account for several methodological issues when specifying and conducting RCTs using these novel tools.

Identification of Patient Perceptions That Can Affect the Uptake of Interventions Using Biometric Monitoring Devices: Systematic Review of Randomized Controlled Trials.

BACKGROUND: Biometric monitoring devices (BMDs) are wearable or environmental trackers and devices with embedded sensors that can remotely collect high-frequency objective data on patients' physiological, biological, behavioral, and environmental contexts (for example, fitness trackers with accelerometer). The real-world effectiveness of interventions using biometric monitoring devices depends on patients' perceptions of these interventions. OBJECTIVE: We aimed to systematically review whether and how recent randomized controlled trials (RCTs) evaluating interventions using BMDs assessed patients' perceptions toward the intervention. METHODS: We systematically searched PubMed (MEDLINE) from January 1, 2017, to December 31, 2018, for RCTs evaluating interventions using BMDs. Two independent investigators extracted the following information: (1) whether the RCT collected information on patient perceptions toward the intervention using BMDs and (2) if so, what precisely was collected, based on items from questionnaires used and/or themes and subthemes identified from qualitative assessments. The two investigators then synthesized their findings in a schema of patient perceptions of interventions using BMDs. RESULTS: A total of 58 RCTs including 10,071 participants were included in the review (the median number of randomized participants was 60, IQR 37-133). BMDs used in interventions were accelerometers/pedometers (n=35, 60%), electrochemical biosensors (eg, continuous glucose monitoring; n=18, 31%), or ecological momentary assessment devices (eg, carbon monoxide monitors for smoking cessation; n=5, 9%). Overall, 26 (45%) trials collected information on patient perceptions toward the intervention using BMDs and allowed the identification of 76 unique aspects of patient perceptions that could affect the uptake of these interventions (eg, relevance of the information provided, alarm burden, privacy and data handling, impact on health outcomes, independence, interference with daily life). Patient perceptions were unevenly collected in trials. For example, only 5% (n=3) of trials assessed how patients felt about privacy and data handling aspects of the intervention using BMDs. CONCLUSIONS: Our review showed that less than half of RCTs evaluating interventions using BMDs assessed patients' perceptions toward interventions using BMDs. Trials that did assess perceptions often only assessed a fraction of them. This limits the extrapolation of the results of these RCTs to the real world. We thus provide a comprehensive schema of aspects of patient perceptions that may affect the uptake of interventions using BMDs and which should be considered in future trials. TRIAL REGISTRATION: PROSPERO CRD42018115522; https://tinyurl.com/y5h8fjgx.

Adaptation and validation of a Spanish version of the treatment burden questionnaire in patients with multiple sclerosis.

BACKGROUND: The Treatment Burden Questionnaire (TBQ) is a self-reported measure of the effect of treatment workload on patient wellbeing. We sought to validate the TBQ in Spanish and use it to estimate the burden of treatment in Argentinian patients with multiple sclerosis (MS). METHODS: The TBQ was forward-backward translated into Spanish. Two focus groups and 25 semi-structured interviews focused on wording and possible item exclusion. Validation was performed in 2 steps. First, 162 patients across a range of MS severity completed the questionnaire. Confirmatory factor analysis assessed the dimensional structure of the TBQ. Construct validity was assessed by studying correlations with fatigue and quality of life (QoL). Then, in a second cohort of 171 patients, we evaluated the association between TBQ scores and patients' sex, age, education level, employment status, type of MS, disease duration, comorbidities, EDSS, pharmacological treatment and medication adherence. RESULTS: The questionnaire presented a 3-factor structure in which burden was related to pharmacological treatment; comprehensive health assistance; and psycho-social-economic context. Composite reliability was > 0.8 for all factors. TBQ showed positive correlation with fatigue (rs = 0.467, p = 0.006), negative correlation with QoL (rs - 0.446, p = 0.009). For the second cohort, total TBQ score was 43 (SD 29). Lowest scores were observed on self-monitoring (0.53, SD 1.3) and highest for administrative load (4.2, SD 3.4). Inverse association was found between the TBQ score and medication adherence (r 0.243 p = 0.001). TBQ scores also correlated with daily patient pill/injection requirements (r 0.175 p = 0.020). Individuals receiving injectable treatment scored higher than patients on oral drugs (total TBQ 51 (SD 32) vs 39 (SD 27) p = 0.002). CONCLUSIONS: The TBQ in Spanish is a reliable instrument and showed adequate correlation with QoL and adherence scales in MS patients. TBQ may benefit health resources allocation and provide tailor therapeutic interventions to construct a minimally disruptive care.

Avoidable waste of research related to outcome planning and reporting in clinical trials.

BACKGROUND: Inadequate planning, selective reporting, and incomplete reporting of outcomes in randomized controlled trials (RCTs) contribute to the problem of waste of research. We aimed to describe such a waste and to examine to what extent this waste could be avoided. METHODS: This research-on-research study was based on RCTs included in Cochrane reviews with a summary of findings (SoF) table. We considered the outcomes reported in the SoF tables as surrogates for important outcomes for patients and other decision makers. We used a three-step approach. (1) First, in each review, we identified, for each important outcome, RCTs that were excluded from the corresponding meta-analysis. (2) Then, for these RCTs, we systematically searched for registrations and protocols to distinguish between inadequate planning (an important outcome was not reported in registries or protocols), selective reporting (an important outcome was reported in registries or protocols but not in publications), and incomplete reporting (an important outcome was incompletely reported in publications). (3) Finally, we assessed, with the consensus of five experts, the feasibility and cost of measuring the important outcomes that were not planned. We considered inadequately planned or selectively or incompletely reported important outcomes as avoidable waste if the outcome could have been easily measured at no additional cost based on expert evaluation. RESULTS: Of the 2711 RCTs included in the main comparison of 290 reviews, 2115 (78%) were excluded from at least one meta-analysis of important outcomes. Every trial contributed to 55%, on average, of the meta-analyses of important outcomes. Of the 310 RCTs published in 2010 or later, 156 were registered. Inadequate planning affected 79% of these RCTs, whereas incomplete and selective reporting affected 41% and 15%, respectively. For 63% of RCTs, we found at least one missing important outcome for which the waste was avoidable and for 30%, the waste was avoidable for all important outcomes. CONCLUSIONS: Most of the RCTs included in our sample did not contribute to all the important outcomes in meta-analyses, mostly because of inadequate planning or incomplete reporting. A large part of this waste of research seemed to be avoidable.

Frugal innovation in medicine for low resource settings.

Whilst it is clear that technology is crucial to advance healthcare: innovation in medicine is not just about high-tech tools, new procedures or genome discoveries. In constrained environments, healthcare providers often create unexpected solutions to provide adequate healthcare to patients. These inexpensive but effective frugal innovations may be imperfect, but they have the power to ensure that health is within reach of everyone. Frugal innovations are not limited to low-resource settings: ingenuous ideas can be adapted to offer simpler and disruptive alternatives to usual care all around the world, representing the concept of "reverse innovation". In this article, we discuss the different types of frugal innovations, illustrated with examples from the literature, and argue for the need to give voice to this neglected type of innovation in medicine.

Discordance Between Drug Adherence as Reported by Patients and Drug Importance as Assessed by Physicians.

PURPOSE: Among patients on long-term medical therapy, we compared (1) patient and physician assessments of drug adherence and of drug importance and (2) drug adherence reported by patients with drug importance as assessed by their physicians. METHODS: We recruited to the study patients receiving at least 1 long-term drug treatment from both hospital and ambulatory settings in France. We compared drug adherence reported by patients and drug importance assessed by physicians using Spearman correlation coefficients. Reasons for nonadherence were collected with open-ended questions and classified as intentional or unintentional. RESULTS: Between April and August 2014, we recruited 128 patients taking 498 drugs. Patients and physicians showed only weak agreement in their assessments of drug adherence (r = -0.25; 95% CI, -0.37 to -0.11) and drug importance (r = 0.07; 95% CI, 0.00 to 0.13). We did not find any correlation between physician-assessed drug importance and patient-reported drug adherence (r = -0.04; 95% CI, -0.14 to 0.06). In all, 94 (18.9%) of the drugs that physicians considered important were not correctly taken by patients. Patients intentionally did not adhere to 26 (48.1%) of the drugs for which they reported reasons for nonadherence. CONCLUSIONS: We found substantial discordance between patient and physician evaluations of drug adherence and drug importance. Nearly 20% of drugs considered important by physicians were not correctly taken by patients. These findings highlight the need for better patient-physician collaboration in drug treatment.