Clinical Trials For Treatment Research Articles

Use of patient-reported global assessment measures in clinical trials of chronic pain treatments: ACTTION systematic review and considerations.

Establishing clinically meaningful changes in pain experiences remains important for clinical trials of chronic pain treatments. Regulatory guidance and pain measurement initiatives have recommended including patient-reported global assessment measures (eg, Patient-Global Impression of Change [PGIC]) to aid interpretation of within-patient differences in domain-specific clinical trial outcomes (eg, pain intensity). The objectives of this systematic review were to determine the frequency of global assessment measures inclusion, types of measures, domains assessed, number and types of response options, and how measures were analyzed. Of 4172 abstracts screened across 6 pain specialty journals, we reviewed 96 clinical trials of chronic pain treatments. Fifty-two (54.2%) studies included a global assessment measure. The PGIC was most common (n = 28; 53.8%), with relatively infrequent use of other measures. The majority of studies that used a global assessment measure (n = 31; 59.6%) assessed change or improvement in an unspecified domain. Others assessed overall condition severity (n = 9; 17.3%), satisfaction (n = 8; 15.4%), or overall health status/recovery (n = 5; 9.6%). The number, range, and type of response options were variable and frequently not reported. Response options and reference periods even differed within the PGIC. Global assessment measures were most commonly analyzed as continuous variables (n = 24; 46.2%) or as dichotomous variables with positive categories combined to calculate the proportion of participants with a positive response to treatment (n = 18; 34.6%). This review highlights the substantial work necessary to clarify measurement and use of patient global assessment in chronic pain trials and provides short- and long-term considerations for measure selection, reporting and analysis, and measure development.

Treating epidermolytic ichthyosis and ichthyosis with confetti with epidermal autografts cultured from revertant skin.

No efficient treatment has been established yet for epidermolytic ichthyosis (EI) caused by pathogenic variants in KRT1 or KRT10. Patients with ichthyosis with confetti (IWC) show multiple normal-appearing spots, caused by the revertant somatic recombination of pathogenic variants that occurs at each spot independently. Additionally, some patients with EI have large areas of normal skin due to revertant postzygotic mosaicism. To assess the feasibility transplanting cultured epidermal autografts (CEAs) produced from revertant epidermal keratinocytes in patients with EI and IWC. We performed a clinical trial of treatment with CEAs produced from each patient's own revertant epidermal keratinocytes as a proof-of-concept study. This is a single-arm, open (masking not used), uncontrolled, single-assignment, treatment purpose study. The primary outcome was the rate of areas without the recurrence of ichthyosis lesions 4 weeks after the final transplant (%). The secondary outcome was the rate of areas without the recurrence of ichthyosis lesions 24 weeks after initial transplantation (%). We successfully produced CEAs from the genetically confirmed revertant skin of the two mosaic EI patients and one IWC patient and genetically confirmed that CEAs mainly consist of revertant wild-type cells by amplicon sequencing and droplet digital PCR analysis. Single-cell RNA sequencing analysis confirmed the normal proliferation and safety profiling of CEAs. CEAs were transplanted to desquamated lesional sites of the patients. Four weeks after this transplantation, the rate of areas without the recurrence of ichthyosis lesions in the three cases was 39.52%, 100.0%, and 100.0% respectively, although the recurrence of ichthyosis lesions was seen at the site of CEA transplantation in all three patients at 24 weeks after transplantation. CEAs from normal skin have the potential to be a safe and local treatment option for EI and IWC. jRCTb041190097.

Targeting gut microbiota for immunotherapy of diseases

Targeting gut microbiota for immunotherapy of diseases

A brief mindfulness-based intervention for stress, pain, emotion and attention regulation in military service members with mild traumatic brain injury.

The primary aim of this study was to conduct an open pilot clinical trial of a brief mindfulness-based intervention for persistent postconcussion symptoms that occur after mild traumatic brain injury in military service members. For many service members, operational tempo and other time constraints may prevent them from completing a standard mindfulness-based stress reduction course. Thus, this study sought to examine the effectiveness of a five-session intervention called mindfulness-based stress, pain, emotion, and attention regulation (MSPEAR). Participants were active duty service members with a history of mild traumatic brain injury (TBI) and persisting postconcussion symptoms, all of whom were recruited from an outpatient TBI rehabilitation program at a military treatment facility. Of the 38 service members that were initially enrolled, 25 completed the 5-session MSPEAR intervention, and 20 returned for a 5-week follow-up evaluation. Questionnaires assessing perceived stress, positive affect, pain interference and catastrophizing, sleep disturbances, perceived behavioral and attention regulation, self-efficacy and satisfaction with life were administered at preintervention, postintervention, and at 5-week follow-up intervals. Neuropsychological testing at preintervention and 5-week follow-up included performance validity measures, attention, working memory, and executive function measures. T-tests were run to compare for questionnaire measures at preintervention (Time 1) to postintervention (Time 2). Repeated analysis of variances were conducted to compare questionnaire and neuropsychological measures at Time 1, Time 2, and at Time 3 which is the 5-week follow-up. Improvements in perceived stress, positive affect, behavioral regulation, metacognition, sleep disturbance, self-efficacy, and satisfaction with life were found immediately after the MSPEAR intervention and were maintained at the 5-week follow-up. Magnification and helplessness aspects of pain catastrophizing improved when comparing preintervention to the 5-week follow-up. Pain interference was not significantly different across study assessment times. Neuropsychological testing revealed improvements in sustained attention, working memory, cognitive flexibility, and inhibitory control when comparing preintervention to the 5-week follow-up assessment. The MSPEAR intervention appears to show promise as a brief and effective therapy for specific postconcussion symptoms after mild traumatic brain injury in military service members. Each of the components of MSPEAR including stress, pain catastrophizing, emotion and attention regulation showed improvements in this study, and bears further investigation in a larger scale, preferably randomized controlled trial in those active duty military service members who experience persisting symptoms after a mild traumatic brain injury.

OCT analysis of preoperative foveal microstructure in recent-onset macula-off rhegmatogenous retinal detachment: visual acuity prognostic factors

BackgroundTo evaluate, in patients undergoing macula-off rhegmatogenous retinal detachment surgery (RRD), the correlation between preoperative optical coherence tomography (OCT) morphological features and postoperative visual acuity.MethodsRetrospective interventional non-randomised clinical trial on...

An open pilot trial of a behavioural intervention to reduce violence by young adults with early psychosis receiving treatment in an early intervention services setting: A protocol.

Despite the public health impact of violence among young adults with psychosis, behavioural interventions to reduce the risk of engaging in violence remain rare. For young adults with early psychosis, cognitive behavioural therapy (CBT)-based psychotherapy has efficacy in reducing impairment and improving functioning. However, no CBT-based intervention to reduce violence has been formally adapted for young adults with early psychosis. This protocol outlines the first clinical trial of a behavioural intervention to reduce violence for young adults with early psychosis. This study is set in an early intervention services (EIS) setting and seeks to adapt and pilot Psychological Intervention for Complex PTSD and Schizophrenia-Spectrum Disorder (PICASSO), a CBT-based intervention, through an iterative process utilizing mixed-methods assessments. All research will occur at OnTrackNY, the largest EIS program in the United States. This study will consist of an open pilot trial, with four EIS clinicians delivering the intervention to one to two EIS participants per round. In this mixed-methods study, both quantitative measures (acceptability, feasibility and hypothesized mediators of target outcome collected on a weekly basis) and qualitative interviews (with EIS clinicians at weeks 4, 8 and 12) will be conducted. Transcripts will be analyzed using thematic content analysis. Two to three rounds of iterative modifications are anticipated (n = 10-16 EIS participants total). Recruitment began in February 2024 and is expected to continue over a 9-12-month period. Because violent behaviour causes interpersonal disruptions such as incarceration and increased caregiver burden, an innovative intervention to reduce violence risk could have broader health impact for this vulnerable population. Adapting the PICASSO intervention to the EIS setting will optimize its acceptability and feasibility by the intended target population.

Abstract PO1-06-03: Efficacy of First-line Treatments for Hormone Receptor-positive, Human Epidermal Growth Factor Receptor 2-positive Metastatic Breast Cancer: A Systematic Literature Review and Network Meta-analysis Feasibility Assessment

Abstract Background: A comprehensive summary of clinical evidence for first-line (1L) treatments for hormone receptor-positive, human epidermal growth factor receptor 2-positive (HR+/HER2+) advanced or metastatic breast cancer (mBC) is needed to understand which treatments have been evaluated and the outcomes associated with different treatments. Understanding the available clinical evidence for HR+/HER2+ mBC 1L treatments can also inform the feasibility of network meta-analyses (NMAs) to estimate relative treatment effects where head-to-head trials are not available. The objective was to prepare a systematic summary of clinical trials of 1L treatments for HR+/HER2+ mBC and assess the feasibility of NMAs for key efficacy outcomes. Methods: A systematic literature review (SLR) was conducted per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Clinical trials evaluating 1L treatments for adults with HR+/HER2+ mBC published between January 2000 and January 2023 were identified via predefined searches of databases (Embase, MEDLINE, Cochrane Library), relevant congress proceedings, and ClinicalTrials.gov (updating a previous SLR covering January 2000 to December 2020). Study design characteristics, patient characteristics, and efficacy outcomes were extracted from identified trials. An NMA feasibility assessment that considered network connectivity and cross-study heterogeneity was conducted for four efficacy outcomes of interest: progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and clinical benefit rate (CBR). Results: After screening, 37 records reporting on 23 unique studies (11 randomized controlled trials [RCTs] and 12 single-arm trials; 35 study arms in total) were selected. Included trials were mostly phase II or phase III multi-country studies that evaluated a HR+ or HER2+ population, with outcomes being reported for the subgroup of patients with the HR+/HER2+ subtype. Treatments evaluated included one or two anti-HER2 therapies (AHTs) + endocrine therapy (ET) (5/35 study arms), AHTs + chemotherapy (CT) (20/35), AHTs + ET + CT (2/35), AHTs alone (5/35), and ET alone (3/35). For HR+/HER2+ patients, PFS and OS were reported by 17/23 and 10/23 studies, respectively. Reported median PFS and OS ranged from 2.4-23.7 months and 23.9-66.7 months, respectively. Among the 11 included RCTs, hazard ratios and/or Kaplan-Meier curves, which were considered a requirement for NMAs for time to event outcomes, were reported for PFS and OS by 9 and 6 studies, respectively. Among these studies, reported median PFS and OS ranged from 2.4-19.2 months and 23.9-57.9 months, respectively. For HR+/HER2+ patients, ORR and CBR were reported by 13/23 and 6/23 studies, respectively. Assuming all CTs could be considered equivalent treatments and all ETs could be considered equivalent treatments, NMAs involving networks of 9, 6, 6, and 3 treatments were feasible for PFS, OS, ORR, and CBR, respectively. Some patient characteristics including time since mBC diagnosis and proportion with bone metastases were not reported consistently across trials. However, included studies were broadly comparable based on study design characteristics, outcome definitions and other reported patient characteristics such as age and Eastern Cooperative Oncology Group performance status. Conclusion: Clinical trials in 1L HR+/HER2+ mBC have evaluated various combinations of AHTs, CTs, and ETs, with most study arms being AHTs + CT. Although efficacy outcomes of interest were not consistently reported across trials, NMAs were found to be feasible for PFS, OS, ORR, and CBR based on available data. Citation Format: Priyanka Sharma, Chau Dang, Christopher Drudge, Amrita Debnath, Manvir Rai, Eric Gauthier, Edward Broughton. Efficacy of First-line Treatments for Hormone Receptor-positive, Human Epidermal Growth Factor Receptor 2-positive Metastatic Breast Cancer: A Systematic Literature Review and Network Meta-analysis Feasibility Assessment [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-06-03.

Abstract PO3-27-08: Geographic Distribution and Accessibility of Clinical Trials for Advanced-Stage Breast Cancer in the United States: A Focus on Rural and Minority Health Disparities

Abstract Background: Our research examines the geographical distribution and accessibility of clinical trials for metastatic breast cancer patients in the U.S., spotlighting the challenges faced by rural communities and minority groups. Prior research indicated nearly half of these patients would have to commute over an hour to reach a trial site. [1] Our study provides a refreshed perspective on this issue, offering a more comprehensive analysis. Methods: Utilizing the ClinicalTrials.gov portal, we identified active interventional clinical trials for metastatic breast cancer patients as of November 25, 2022. We obtained distinct zip codes linked to these trials and, using 2020 census data, estimated the proportion of the U.S. populace residing within specific distances from these sites. Our analysis encompassed ethnicity, and other socio-economic parameters. Using GIS software, we also developed illustrative maps to visually represent the U.S. clinical trial accessibility landscape. Results: The majority of Americans diagnosed with metastatic breast cancer have clinical trials within their reach. A significant 81.8% of the U.S. populace resides within a 30-mile radius of a relevant clinical trial site. However, there is significant variation among ethnic groups, especially among American Indians, where 56.5% live within 30 miles of a clinical trial site. Conclusions: While a commendable 81.8% of the U.S. population resides within 30 miles of a metastatic breast cancer clinical trial site, our data underscores the uneven geographical spread of these trials. Our findings underscore the need for strategic initiatives to ensure clinical trials are within reach for every individual, irrespective of their location or background. Reference: 1. Galsky MD, Stensland KD, McBride RB, Latif A, Moshier E, Oh WK, Wisnivesky J. Geographic accessibility to clinical trials for advanced cancer in the United States. JAMA Intern Med. 2015 Feb;175(2):293-5. PMID: 25437434. Map of 30-, 60-, and 120-mile buffers from clinical trial sites open to patients with metastatic breast cancer. The U.S. Population living withing 30-, 60-, and 120-miles of an open clinical trial site for patients with metastatic breast cancer. Citation Format: Emily Westergard, Abigail Swenson, Zachary Schroeder, Wade Swenson. Geographic Distribution and Accessibility of Clinical Trials for Advanced-Stage Breast Cancer in the United States: A Focus on Rural and Minority Health Disparities [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-27-08.

73. Preliminary Efficacy Findings for a Placebo Controlled Randomized Clinical Trial of a Novel Executive Working Memory Training Intervention for Adolescents With ADHD

73. Preliminary Efficacy Findings for a Placebo Controlled Randomized Clinical Trial of a Novel Executive Working Memory Training Intervention for Adolescents With ADHD

Arginine vasopressin deficiency: diagnosis, management and the relevance of oxytocin deficiency.

Polyuria-polydipsia syndrome can be caused by central diabetes insipidus, nephrogenic diabetes insipidus or primary polydipsia. To avoid confusion with diabetes mellitus, the name 'central diabetes insipidus' was changed in 2022 to arginine vasopressin (AVP) deficiency and 'nephrogenic diabetes insipidus' was renamed as AVP resistance. To differentiate the three entities, various osmotic and non-osmotic copeptin-based stimulation tests have been introduced in the past decade. The hypertonic saline test plus plasma copeptin measurement emerged as the test with highest diagnostic accuracy, replacing the water deprivation test as the gold standard in differential diagnosis of the polyuria-polydipsia syndrome. The mainstay of treatment for AVP deficiency is AVP replacement with desmopressin, a synthetic analogue of AVP specific forAVP receptor 2 (AVPR2), which usually leads to rapid improvements in polyuria and polydipsia. The main adverse effect of desmopressin is dilutional hyponatraemia, which can be reduced by regularly performing the so-called desmopressin escape method. Evidence from the past few years suggests an additional oxytocin deficiency in patients with AVP deficiency. This potential deficiency should be further evaluated in future studies, including feasible provocation tests for clinical practice and interventional trials with oxytocin substitution.

Regulatory gaps and research waste in clinical trials involving women with metastatic breast cancer in Germany

Background Non-publication, incomplete publication and excessively slow publication of clinical trial outcomes contribute to research waste and can harm patients. While research waste in German academic trials is well documented, research waste in Germany related to a specific disease area across non-commercial and commercial sponsors has not previously been assessed. Methods In this cohort study, we used public records from three clinical trial registries to identify 70 completed or terminated clinical trials involving women with metastatic breast cancer with trial sites in Germany. We then searched registries and the literature for trial outcomes and contacted sponsors about unreported studies. Results We found that 66/70 trials (94.3%) had made their results public. Only 13/70 (18.6%) trials had reported results within one year of completion as recommended by the World Health Organisation (WHO). The outcomes of 4/70 trials (5.7%) had not been made public at all, but only one of those trials had recruited a significant number of patients. Conclusions Discussions about research waste in clinical trials commonly focus on weakly designed or unreported trials. We believe that late reporting of results is another important form of research waste. In addition, a discussion regarding the appropriate ethical and legal rules for reporting the results of terminated trials might add value. German legislation now requires sponsors to upload the results of some clinical trials onto a trial registry within one year of trial completion, but these laws only cover around half of all trials. Our findings highlight the potential benefits of extending the scope of national legislation to cover all interventional clinical trials involving German patients.

A sirtuin 6 activator in the pipeline: New perspectives in depressive disorder treatment

Major Depressive Disorder (MDD) is among the most prevalent mental illnesses worldwide. Its symptoms include persistent feelings of sadness, loss of interest in previously enjoyed activities, and a lack of motivation for daily tasks. While FDA-approved medications are available, they often come with side effects, especially those targeting monoamine neurotransmitters like SSRIs and SNRIs. Thus, there is a need for innovative medications with different mechanisms of action. Sp-624, a derivative of griseofulvin, is currently undergoing clinical trials for MDD treatment. It acts as a sirtuin 6 (SIRT6) activator, offering a novel approach to treating this disorder. This article discusses the biochemical aspects related to the mechanism of action of sp-624, provides a brief overview of related patents, and highlights ongoing clinical trials involving this substance.

DNA-PK participates in pre-rRNA biogenesis independent of DNA double-strand break repair.

Although DNA-PK inhibitors (DNA-PK-i) have been applied in clinical trials for cancer treatment, the biomarkers and mechanism of action of DNA-PK-i in tumor cell suppression remain unclear. Here, we observed that a low dose of DNA-PK-i and PARP inhibitor (PARP-i) synthetically suppresses BRCA-deficient tumor cells without inducing DNA double-strand breaks (DSBs). Instead, we found that a fraction of DNA-PK localized inside of nucleoli, where we did not observe obvious DSBs. Moreover, the Ku proteins recognize pre-rRNA that facilitates DNA-PKcs autophosphorylation independent of DNA damage. Ribosomal proteins are also phosphorylated by DNA-PK, which regulates pre-rRNA biogenesis. In addition, DNA-PK-i acts together with PARP-i to suppress pre-rRNA biogenesis and tumor cell growth. Collectively, our studies reveal a DNA damage repair-independent role of DNA-PK-i in tumor suppression.

Unveiling Pharmacokinetics and Drug Interaction of Linagliptin and Pioglitazone HCl in Rat Plasma Using LC-MS/MS.

The linagliptin (LIN) and pioglitazone HCl (PIO) combination, currently undergoing phase III clinical trials for diabetes mellitus treatment, demonstrated significant improvements in glycemic control. However, the absence of an analytical method for simultaneous determination in biological fluids highlights a crucial gap. This underscores the pressing need for sensitive bioanalytical methods, emphasizing the paramount importance of developing such tools to advance diabetes management strategies and enhance patient care. Herein, a sensitive reverse-phase high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry method was developed for simultaneous determination of LIN and PIO in rat plasma using alogliptin as an internal standard. Chromatographic separation was performed on an Agilent Eclipse Plus C18 (4.6 × 100 mm, 3.5 μm) using an isocratic mobile phase system consisting of ammonium formate (pH 4.5) and methanol using an acetonitrile-induced protein precipitation technique for sample preparation. Multiple reaction monitoring in positive ion mode was used for quantitation of the precursor to production at m/z 473.2 → 419.9 for LIN, 357.1 → 134.2 for PIO, and 340.3 → 116.1 for ALO. The linearity range was 0.5 to 100 and 1 to 2000 ng/mL for LIN and PIO, respectively. The developed method was validated as per US-FDA guidelines and successfully applied to clinical pharmacokinetic and drug-drug interaction studies with a single oral administration of LIN and PIO in rat plasma. Pharmacokinetic parameters of LIN were significantly influenced by the concomitant administration of PIO and vice versa. Molecular modeling revealed the significant interaction of LIN and PIO with P-glycoprotein. Therefore, the drug-drug interaction between LIN and PIO deserves further study to improve drug therapy and prevent dangerous adverse effects.

COVID-19 clinical trial participation and awareness in Texas

ABSTRACT The COVID-19 pandemic required the rapid development of COVID-19 vaccines and treatments, necessitating quick yet representative clinical trial enrollment to evaluate these preventive measures. However, misinformation around the COVID-19 pandemic and general concerns about clinical trial participation in the U.S. hindered clinical trial enrollment. This study assessed awareness of, willingness to participate in, and enrollment in COVID-19 vaccine and treatment clinical trials in Texas. A quota sample of 1,089 Texas residents was collected online from June – July 2022. Respondents were asked if they were aware of, willing to participate in, and had enrolled in clinical trials for COVID-19 vaccines or treatments. Overall, 45.8% of respondents reported being aware of clinical trials for COVID-19 treatments or vaccines, but only 21.7% knew how to enroll and only 13.2% had enrolled in a COVID-19 clinical trial. Respondents with bachelor’s or graduate degrees were more likely to be aware of clinical trials, more likely to have enrolled in trials, and more willing to participate in treatment trials. Women were less willing to participate and less likely to have enrolled in COVID-19 clinical trials than men. Respondents aged 55 years and older were more willing to participate, but less likely to have enrolled in COVID-19 clinical trials than 18-to-24-year-olds. Common reasons given for not participating in clinical trials included concerns that COVID-19 treatments may not be safe, government distrust, and uncertainty about what clinical trial participation would entail. Substantial progress is needed to build community awareness and increase enrollment in clinical trials.

Hope

Duchenne muscular dystrophy (DMD) is a life-shortening genetic condition involving progressive muscular wasting for which there is no hope of recovery at present. The lives of people with DMD, cherished by their families, are systematically marginalised and undervalued by healthcare bureaucracies while enrolment in clinical trials of new treatments offers possibilities of longer-term biomedical solutions. How is hope preserved under such circumstances and what activities can promote a full and meaningful life for those with DMD Ethnographic research within the DMD community in Aotearoa New Zealand provided a basis for addressing these questions and for understanding different concepts of hope and social suffering, the value of life in DMD and disability studies, and how these are shaped by regimes of governmentality.

A qualitative study of using nicotine products for smoking cessation after discharge from residential drug and alcohol treatment in Australia.

Tobacco smoking is highly prevalent among alcohol and other drugs (AOD) service clients and, despite interest in quitting, abstinence is rarely sustained. Nicotine products may assist after discharge from residential treatment services, but little is known about client receptivity to them. This study examined AOD withdrawal service clients' experiences of two types of nicotine products for smoking cessation post-discharge, combination nicotine replacement therapy (cNRT) and nicotine vaping products (NVP). We held semi-structured telephone interviews with 31 Australian AOD service clients in a clinical trial of a 12-week smoking cessation intervention using Quitline support plus cNRT or NVP delivered post-discharge from a smoke-free residential service. We asked about health and social factors, nicotine cravings, Quitline experience, and barriers and facilitators to cNRT or NVP, then thematically analysed data. cNRT and NVP were described by participants as feasible and acceptable for smoking cessation. For most participants, cost limited cNRT access post study, as did difficulty navigating NVP prescription access. Quitline support was valued, but not consistently used, with participants noting low assistance with NVP-facilitated cessation. Participants considered both cessation methods acceptable and socially supported, and sought information on decreasing nicotine use via NVP. AOD service clients highly valued receiving cNRT or NVP with behavioural support for smoking reduction or abstinence. Both interventions were acceptable to service clients. Findings suggest a potential need to examine both whether NVP use should be permitted in this context, and guidance on the individual suitability of cNRT or NVP.

MyTrack+: Human-centered design of an mHealth app to support long-term weight loss maintenance.

A growing body of research has focused on the utility of adaptive intervention models for promoting long-term weight loss maintenance; however, evaluation of these interventions often requires customized smartphone applications. Building such an app from scratch can be resource-intensive. To support a novel clinical trial of an adaptive intervention for weight loss maintenance, we developed a companion app, MyTrack+, to pair with a main commercial app, FatSecret (FS), leveraging a user-centered design process for rapid prototyping and reducing software engineering efforts. MyTrack+ seamlessly integrates data from FS and the BodyTrace smart scale, enabling participants to log and self-monitor their health data, while also incorporating customized questionnaires and timestamps to enhance data collection for the trial. We iteratively refined the app by first developing initial mockups and incorporating feedback from a usability study with 17 university students. We further improved the app based on an in-the-wild pilot study with 33 participants in the target population, emphasizing acceptance, simplicity, customization options, and dual app usage. Our work highlights the potential of using an iterative human-centered design process to build a companion app that complements a commercial app for rapid prototyping, reducing costs, and enabling efficient research progress.

Reporting of interventional clinical trial results in an academic center: a survey of completed studies

BackgroundThe dissemination of clinical trial results is an important scientific and ethical endeavour. This survey of completed interventional studies in a French academic center describes their reporting status.MethodsWe explored all interventional studies sponsored by Rennes University Hospital identified on the French Open Science Monitor which tracks trials registered on EUCTR or clinicaltrials.gov, and provides an automatic assessment of the reporting of results. For each study, we ascertained the actual reporting of results using systematic searches on the hospital internal database, bibliographic databases (Google Scholar, PubMed), and by contacting all principal investigators (PIs). We describe several features (including total budget and numbers of trial participants) of the studies that did not report any results.ResultsThe French Open Science Monitor identified 93 interventional studies, among which 10 (11%) reported results. In contrast, our survey identified 36 studies (39%) reporting primary analysis results and an additional 18 (19%) reporting results for secondary analyses (without results for their primary analysis). The overall budget for studies that did not report any results was estimated to be €5,051,253 for a total of 6,735 trial participants. The most frequent reasons for the absence of results reported by PIs were lack of time for 18 (42%), and logistic difficulties (e.g. delay in obtaining results or another blocking factor) for 12 (28%). An association was found between non-publication and negative results (adjusted Odds Ratio = 4.70, 95% Confidence Interval [1.67;14.11]).ConclusionsEven allowing for the fact that automatic searches underestimate the number of studies with published results, the level of reporting was disappointingly low. This amounts to a waste of trial participants' implication and money. Corrective actions are needed.Trial registrationhttps://osf.io/q5hcs

Placebo Control and Blinding in Randomized Trials of Procedural Interventions

Unlike medications, procedural interventions are rarely trialed against placebo prior to becoming accepted in clinical practice. When placebo-controlled trials are eventually conducted, procedural interventions may be less effective than previously believed. To investigate the importance of including a placebo arm in trials of surgical and interventional procedures by comparing effect sizes from trials of the same procedure that do and do not include a placebo arm. Searches of MEDLINE and Embase identified all placebo-controlled trials for procedural interventions in any specialty of medicine and surgery from inception to March 31, 2019. A secondary search identified randomized clinical trials assessing the same intervention, condition, and end point but without a placebo arm for paired comparison. Placebo-controlled trials of anatomically site-specific procedures requiring skin incision or endoscopic techniques were eligible for inclusion; these were then matched to trials without placebo control that fell within prespecified limits of heterogeneity. Random-effects meta-regression, with placebo and blinding as a fixed effect and intervention and end point grouping as random effects, was used to calculate the impact of placebo control for each end point. Data were analyzed from March 2019 to March 2020. End points were examined in prespecified subgroups: patient-reported or health care professional-assessed outcomes, quality of life, pain, blood pressure, exercise-related outcomes, recurrent bleeding, and all-cause mortality. Ninety-seven end points were matched from 72 blinded, placebo-controlled trials (hereafter, blinded) and 55 unblinded trials without placebo control (hereafter, unblinded), including 111 500 individual patient end points. Unblinded trials had larger standardized effect sizes than blinded trials for exercise-related outcomes (standardized mean difference [SMD], 0.59; 95% CI, 0.29 to 0.89; P < .001) and quality-of-life (SMD, 0.32; 95% CI, 0.11 to 0.53; P = .003) and health care professional-assessed end points (SMD, 0.40; 95% CI, 0.18 to 0.61; P < .001). The placebo effect accounted for 88.1%, 55.2%, and 61.3% of the observed unblinded effect size for these end points, respectively. There was no significant difference between unblinded and blinded trials for patient-reported end points (SMD, 0.31; 95% CI, -0.02 to 0.64; P = .07), blood pressure (SMD, 0.26; 95% CI, -0.10 to 0.62; P = .15), all-cause mortality (odds ratio [OR], 0.23; 95% CI, -0.26 to 0.72; P = .36), pain (SMD, 0.03; 95% CI, -0.52 to 0.57; P = .91), or recurrent bleeding events (OR, -0.12; 95% CI, -1.11 to 0.88; P = .88). The magnitude of the placebo effect found in this systematic review and meta-regression was dependent on the end point. Placebo control in trials of procedural interventions had the greatest impact on exercise-related, quality-of-life, and health care professional-assessed end points. Randomized clinical trials of procedural interventions may consider placebo control accordingly.