Outcome Measure In Clinical Trials Research Articles

Data collection methods for patient-reported outcome measures in cancer randomised controlled trials: a protocol for a rapid scoping review

BackgroundThere are different modes and ways to assess patient-reported outcomes (PROs) in clinical trials. However, there is little systematic information on how often different modes of assessment (MOA) are used...

Language use predicts symptoms of fragile X-associated tremor/ataxia syndrome in men and women with the FMR1 premutation

Fragile X-associated tremor/ataxia syndrome (FXTAS) is an age-related neurodegenerative disorder caused by a premutation of the FMR1 gene on the X chromosome. Despite the pervasive physical and cognitive effects of FXTAS, no studies have examined language in symptomatic males and females, limiting utility as an outcome measure in clinical trials of FXTAS. The goal of this work is to determine (a) the extent to which male and female FMR1 premutation carriers with FXTAS symptoms differ in their language use and (b) whether language production predicts FXTAS symptoms. Thirty-one individuals with the FMR1 premutation (21M, 10F), ages 58–85 years with some symptoms of FXTAS, were recruited from a larger cross-sectional study. Participants completed a five-minute monologic language sample. Language transcripts were assessed for rate of dysfluencies, lexical-semantics, syntax, and speech rate. Multivariable linear and ordinal regressions were used to predict FXTAS-associated symptoms, cognitive functioning, and executive functioning. Males and females did not differ in their language use. Language production predicted FXTAS symptom severity, cognitive functioning, and executive functioning. Language production difficulties may co-occur with FXTAS-associated symptoms and may be a viable outcome measure in future clinical trials, with future research needed.

Symptoms across the phases of the migraine cycle from the patient's perspective: Results of the MiCOAS qualitative study.

To better understand the breadth and frequency of symptoms across the phases of the migraine cycle using data captured from qualitative patient interviews conducted through the Migraine Clinical Outcome Assessment System (MiCOAS) project. People living with migraine experience a range of symptoms across the pre-headache, headache, post-headache, and interictal phases of the migraine cycle. Although clinical diagnostic criteria and clinical trial endpoints focus largely on cardinal symptoms or monthly migraine days, migraine symptom profiles are far more complex. As a part of the MiCOAS project, semi-structured qualitative interviews were undertaken to better understand the migraine-related symptomology from the patient's viewpoint. This concept elicitation study used iterative purposeful sampling to select 40 people with self-reported medical diagnosis of migraine for interviews that were conducted via audio-only web conferencing. Key topics related to migraine symptoms, including mood/emotion symptoms, were identified using content analysis. Interview transcripts were also coded to reflect the phase of migraine under discussion, so that patient experiences could be compared by phase. Forty participants (50%, n = 20 episodic migraine; 50%, n = 20 chronic migraine), aged from 21 to 70 years old reported a total of 60 unique symptoms, which were categorized into 30 broader symptom categories. Participants reported between 7 and 22 unique symptom categories across all phases. During pre-headache and headache, participants reported a median of 7.5 (interquartile range [IQR] = 5.5) and 8 (IQR = 4.0) different symptom categories compared to 4 (IQR = 3.0) and 1.5 (IQR = 2.5) for the post-headache and interictal periods, respectively. Head pain during the headache phase was the only universally reported symptom (100%, n = 40). Pooling across all phases, the next most reported symptoms were light sensitivity (93%, n = 37), nausea (88%, n = 35), irritability/impatience (83%, n = 24), sound sensitivity (80%, n = 32), and fatigue/exhaustion (80%, n = 32). One or more interictal symptoms were reported by 73% (n = 29) of participants and included mood/emotion symptoms, such as anxiety (30%, n = 12), depression (18%, n = 7), and anger (15%, n = 6), as well as cardinal symptoms, such as light sensitivity (13%, n = 5) and nausea (13%, n = 5). Patients experience a range of symptoms across the phases of the migraine cycle. Results often aligned with clinical expectations, but non-cardinal migraine-related symptoms were reported both inside and outside the headache phase, including between attacks. These discoveries highlight the importance of assessing a range of symptoms and timing when developing patient-reported outcome measures for migraine clinical trials.

Validating New Symptom Emergence as a Patient-Centric Outcome Measure for PD Clinical Trials

IntroductionTracking of emergent symptoms (ES) in de novo Parkinson Disease (PD) patients using Parts Ib and II of the MDS-UPDRS rating scale has been proposed as an outcome measure for PD clinical trials, based on observations in the Safety, Tolerability and Efficacy Assessment of Isradipine for PD (STEADY-PD3) clinical trial. MethodsIndividual item-level data was extracted from the SURE-PD3 study (coded as “PD-1018” in the C-path pooled dataset). We sought to confirm the observations made in the STEADY-PD3 dataset by analyzing data from a different Phase 3 clinical trial, the Phase 3 Study of Urate Elevation in Parkinson Disease (SURE-PD3), in which MDS-UPDRS was assessed more frequently than the 12-month intervals in STEADY-PD3, using similar methodology. ResultsWe were able to broadly validate results that demonstrated the frequency of ES, lack of impact of the introduction of symptomatic medications, and in the reduction in sample size required to demonstrate slowing of disease progression at a group level compared with the traditional total MDS-UPDRS summed score scoring methods. Counts of ES generally correlated modestly with summed MDS-UPRDS scores, both for the various sub-parts and for the overall scale as well. However, instability of individual item responses, especially during the first 6 months of observation complicated the assessment of the temporal evolution and stability of ES over time in the course of the SURE-PD3 study. ConclusionFurther validation using data sets with frequent administration of MDS-UPDRS is necessary to assess value of this approach as an outcome measure in PD clinical trials.

A Comparison of Optical Coherence Tomography Angiography Metrics and Artifacts on Scans of Different Sizes in Diabetic Macular Ischemia: The effect of different size scans on DMI evaluation

PURPOSEChanges in the foveal avascular zone (FAZ) metrics over time are key outcome measures for clinical trials in diabetic macular ischemia (DMI). However, artifacts and automatically delineated FAZ measurements may influence the results. We aimed to compare the artifact frequency and FAZ metrics on 3 × 3 versus 6 × 6 mm optical coherence tomography angiography (OCTA) macular scans in patients with DMI. DESIGNProspective, comparative image quality analysis with one-year follow-up. METHODSPatients with diabetic retinopathy (DR) were recruited if they presented with OCTA evidence of DMI, defined as an automated FAZ (aFAZ) ≥0.5 mm2 or parafoveal capillary nonperfusion (CNP) ≥1 quadrant if the aFAZ <0.5 mm2. Only those who had both size scans were included in the analysis. The types of artifacts and FAZ delineation errors were graded before manual correction. After excluding scans with poor quality, the aFAZ, corrected FAZ (cFAZ), whole image superficial vessel density (wiSVD), and whole image deep vessel density (wiDVD) were compared on both size scans. RESULTSFifty-seven patients (81 eyes) with paired OCTA 3 × 3 and 6 × 6 mm scans at baseline were included in the image quality analysis. The 6 × 6 mm scan presented with more severe motion artifact (P = .02). Conversely, the 3 × 3 mm scans were more susceptible to mild decentration (P = .009). After removing all the poor-quality images, 55 eyes with both size scans entered the longitudinal analysis. The 3 × 3 mm FAZ was significantly larger than the 6 × 6 mm FAZ using either aFAZ or cFAZ (both P < .05). In contrast, the 6 × 6 mm wiSVD and wiDVD were remarkably higher than those on the 3 × 3 mm scans (both P < .001). There was a steady increase in cFAZ over one year on both size scans (both P < .01). However, the 3 × 3 mm aFAZ decreased numerically at 52 weeks (P = .02). After reviewing all the scans, poor identification of parafoveal CNP was the most common reason for erroneous aFAZ delineation. CONCLUSIONSIn DMI, the FAZ metrics are best evaluated on the 3 × 3 scan due to better resolution. However, manual correction of the FAZ margin is needed. The frequency of artifacts and aFAZ delineation errors suggest that further technical refinement is required.

Leveraging Artificial Intelligence to Optimize Transcranial Direct Current Stimulation for Long COVID Management: A Forward-Looking Perspective.

Long COVID (Coronavirus disease), affecting millions globally, presents unprecedented challenges to healthcare systems due to its complex, multifaceted nature and the lack of effective treatments. This perspective review explores the potential of artificial intelligence (AI)-guided transcranial direct current stimulation (tDCS) as an innovative approach to address the urgent need for effective Long COVID management. The authors examine how AI could optimize tDCS protocols, enhance clinical trial design, and facilitate personalized treatment for the heterogeneous manifestations of Long COVID. Key areas discussed include AI-driven personalization of tDCS parameters based on individual patient characteristics and real-time symptom fluctuations, the use of machine learning for patient stratification, and the development of more sensitive outcome measures in clinical trials. This perspective addresses ethical considerations surrounding data privacy, algorithmic bias, and equitable access to AI-enhanced treatments. It also explores challenges and opportunities for implementing AI-guided tDCS across diverse healthcare settings globally. Future research directions are outlined, including the need for large-scale validation studies and investigations of long-term efficacy and safety. The authors argue that while AI-guided tDCS shows promise for addressing the complex nature of Long COVID, significant technical, ethical, and practical challenges remain. They emphasize the importance of interdisciplinary collaboration, patient-centered approaches, and a commitment to global health equity in realizing the potential of this technology. This perspective article provides a roadmap for researchers, clinicians, and policymakers involved in developing and implementing AI-guided neuromodulation therapies for Long COVID and potentially other neurological and psychiatric conditions.

Exploration of alive-and-ventilator free days as an outcome measure for clinical trials of Resuscitative interventions.

Outcome selection is a critically important aspect of clinical trial design. Alive-and-ventilator free days is an outcome measure commonly used in critical care clinical trials, but has not been fully explored in resuscitation science. A simulation study was performed to explore approaches to the definition and analysis of alive-and-ventilator free days in cardiac arrest populations. Data from an in-hospital cardiac arrest observational cohort and from the Pragmatic Airway Resuscitation Trial were used to inform and conduct the simulations and validate approaches to alive-and-ventilator free days measurement and analysis. Alive-and-ventilator-free days is a flexible outcome measure in cardiac arrest populations. An approach to alive-and-ventilator free days that assigns -1 days when return of spontaneous circulation is not achieved provides a wider distribution of the outcome and improves statistical power. The optimal approach to the analysis of alive-and-ventilator free days varies based on the expected impact of the intervention under study on rates of return of spontaneous circulation, survival, and ventilator-free survival. Alive-and-ventilator free days adds to the armamentarium of clinical trialists in the field of resuscitation science.

Cross-sectional survey study of the natural history of LAMA2-related dystrophy

BackgroundLAMA2-related dystrophies (LAMA2-RD) are a rare group of neuromuscular disorders with a broad spectrum of phenotype severity, ranging from mild to severe. We performed a cross-sectional study of LAMA2-RD through motor function and pulmonary tests to establish the disease's natural history. MethodsForty-four individuals with LAMA2-RD were included and evaluated once through functional outcome measures including Motor Function Measure 32 (MFM32), Revised Upper Limb Module (RULM), goniometry, and Forced Vital Capacity (FVC). Fixed Effect Regression Model (ERM) and Kaplan-Meier curve were used for calculating the rate of the disease progression ResultsPatients were between 2 and 25 years old (mean 11.4), the most frequent phenotype presentation was non-ambulant (N=36, 81.8%) while eight patients (18,2 %) were ambulant. The non-ambulant group presented a more severe progression of the disease. Non-ambulant patients had a 1.85 % decrease in FVC/year against 1.32 %/year among ambulant patients. In the non-ambulant group, there was a 4.2 % drop/year in the MFM32-D2 domain (p<0.00001), a 2.6 % drop/year in the D3 domain (p<0.0001), and a 2.7 % drop/year in the MFM32 global assessment (p<0.0001). However, the non-ambulant group's evaluation of upper limb function through the RULM scale did not show a statistically significant reduction. In the non-ambulant group, elbow and knee retractions worsened 3.22 degrees/year (p=0.00087) and 1.92 degrees/year, respectively. While in those patients who acquired gait, elbow and knee retractions worsened 2.45 degrees/year (p=0.0003) and 1.73 degrees/year (p=0.01), respectively. ConclusionThis study confirmed the progressive nature of LAMA2-RD, both in ambulant and non-ambulant patients. MFM32, FVC, and goniometry were identified as promising outcome measures for natural history studies and clinical trials in LAMA2-RD.

Psychometric properties of MG-ADL items and MG-ADL score: An assessment of distributional characteristics, validity and factor structure in two large datasets

BackgroundThe Myasthenia Gravis–Activities of Daily Living scale (MG-ADL) is an 8-item outcome measure to assess symptoms and functional limitations in myasthenia gravis (MG) patients. The MG-ADL score is an equally weighted level sum score that is used as primary outcome measures in clinical trials, in clinical practice, and as an end-point in health economic evaluation. This data analysis aims to obtain detailed knowledge of measurement properties of MG-ADL items and the MG-ADL score. MethodsCross-sectional data from a real-world prospective study (MRW) were combined with longitudinal data from the ADAPT trial. Outcome measures included were MG-ADL, Quantitative Myasthenia Gravis score (QMG), MG 15-item Quality of Life (MG-QOL15r) and EQ-5D-5L. Patients were categorized by their Myasthenia Gravis Foundation of America (MGFA) clinical classification. The following measurement properties were assessed: distributional characteristics, inter-item correlation, convergent, known groups and construct validity and internal factor structure. ResultsCorrelations of items within MG-ADL dimensions were moderate, while MG-ADL correlations between comparable MG-QOL15r and QMG items were mixed. Known groups validity for the MG-ADL score was demonstrated for MGFA class. Mean MG-ADL item level scores by MGFA class demonstrated construct validity. PCA, including all four outcome measures, resulted in a nine factor solution. DiscussionPsychometric properties of individual MG-ADL items were moderate to good. This study showed that the MG-ADL adequately captures the multidimensional heterogeneous nature of MG. This is, however, accompanied by mixed psychometric performance of the MG-ADL score, which may complicate health economic modelling.Registration: MyRealWorld-MG was registered on November 25, 2019, with registration numberNCT04176211. The ADAPT randomized clinical trial is registered atClinicalTrials.gov(NCT03669588).

Development of a measuring app for systemic sclerosis-related digital ulceration (SALVE: Scleroderma App for Lesion VErification).

To test the hypothesis that photographs (in addition to self-reported data) can be collected daily by patients with systemic sclerosis (SSc) using a smartphone app designed specifically for digital lesions, and could provide an objective outcome measure for use in clinical trials. An app was developed to collect images and patient reported outcome measures (PROMS) including Pain score and the Hand Disability in Systemic Sclerosis-Digital Ulcers (HDISS-DU) questionnaire. Participants photographed their lesion(s) each day for 30 days and uploaded images to a secure repository. Lesions were analysed both manually and automatically, using a machine learning approach. 25 patients with SSc-related digital lesions consented of whom 19 completed the 30-day study, with evaluable data from 27 lesions. Mean (standard deviation [SD]) baseline Pain score was 5.7 (2.4) and HDISS-DU 2.2 (0.9), indicating high lesion and disease-related morbidity. 506 images were used in the analysis (mean number of used images per lesion 18.7, SD 8.3). Mean (SD) manual and automated lesion areas at day 1 were 11.6 (16.0) and 13.9 (16.7) mm2 respectively. Manual area decreased by 0.08mm2 per day (2.4mm2 over 30 days) and automated area by 0.1mm2 (3.0mm2 over 30 days). Average gradients of manual and automated measurements over 30 days correlated strongly (r = 0.81). Manual measurements were on average 40% lower than automated, with wide limits of agreement. Even patients with significant hand disability were able to use the app. Automated measurement of finger lesions could be valuable as an outcome measure in clinical trials.

Application of Digital Tools and Artificial Intelligence to the Myasthenia Gravis Core Examination.

Advances in video image analysis and artificial intelligence provide the opportunity to transform the approach to patient evaluation through objective digital evaluation. We assessed ability to quantitate Zoom video recordings of a standardized neurological examination the myasthenia gravis core examination (MG-CE), which had been designed for telemedicine evaluations. We used Zoom (Zoom Video Communications) videos of patients with myasthenia gravis undergoing the MG-CE. Computer vision in combination with artificial intelligence methods were used to build algorithms to analyze videos with a focus on eye or body motions. For the assessment of examinations involving vocalization, signal processing methods were developed, including natural language processing. A series of algorithms were built that could automatically compute the metrics of the MG-CE. Fifty-one patients with MG with videos recorded twice on separate days and 15 control subjects were assessed once. We were successful in quantitating lid, eye, and arm positions and as well as well as develop respiratory metrics using breath counts. Cheek puff exercise was found to be of limited value for quantitation. Technical limitations included variations in illumination, bandwidth, and recording being done on the examiner side, not the patient. Several aspects of the MG-CE can be quantitated to produce continuous measures via standard Zoom video recordings. Further development of the technology offer the ability for trained, non-physician, health care providers to perform precise examination of patients with MG outside the clinic, including for clinical trials. Advances in video image analysis and artificial intelligence provide the opportunity to transform the approach to patient evaluation. Here, we asked whether video recordings of the typical telemedicine examination for the patient with myasthenia gravis be used to quantitate examination findings? Despite recordings not made for purpose, we were able to develop and apply computer vision and artificial intelligence to Zoom recorded videos to successfully quantitate eye muscle, facial muscle, and limb fatigue. The analysis also pointed out limitations of human assessments of bulbar and respiratory assessments. The neuromuscular examination can be enhanced by advance technologies, which have the promise to improve clinical trial outcome measures as well as standard care.

The use of digital tools in rare neurological diseases towards a new care model: a narrative review

AbstractRare neurological diseases as a whole share peculiar features as motor and/or cognitive impairment, an elevated disability burden, a frequently chronic course and, in present times, scarcity of therapeutic options. The rarity of those conditions hampers both the identification of significant prognostic outcome measures, and the development of novel therapeutic approaches and clinical trials. Collection of objective clinical data through digital devices can support diagnosis, care, and therapeutic research. We provide an overview on recent developments in the field of digital tools applied to rare neurological diseases, both in the care setting and as providers of outcome measures in clinical trials in a representative subgroup of conditions, including ataxias, hereditary spastic paraplegias, motoneuron diseases and myopathies.

Contrast agent-free functional magnetic resonance imaging with matrix pencil decomposition to quantify abnormalities in lung perfusion and ventilation in patients with cystic fibrosis.

Previous studies showed that contrast-enhanced (CE) morpho-functional magnetic resonance imaging (MRI) detects abnormalities in lung morphology and perfusion in patients with cystic fibrosis (CF). Novel matrix pencil decomposition MRI (MP-MRI) enables quantification of lung perfusion and ventilation without intravenous contrast agent administration. To compare MP-MRI with established morpho-functional MRI and spirometry in patients with CF. Thirty-nine clinically stable patients with CF (mean age 21.6 ± 10.7 years, range 8-45 years) prospectively underwent morpho-functional MRI including CE perfusion MRI, MP-MRI and spirometry. Two blinded chest radiologists assessed morpho-functional MRI and MP-MRI employing the validated chest MRI score. In addition, MP-MRI data were processed by automated software calculating perfusion defect percentage (QDP) and ventilation defect percentage (VDP). MP perfusion score and QDP correlated strongly with the CE perfusion score (both r = 0.81; p < 0.01). MP ventilation score and VDP showed strong inverse correlations with percent predicted FEV1 (r = -0.75 and r = -0.83; p < 0.01). The comparison of visual and automated parameters showed that both MP perfusion score and QDP, and MP ventilation score and VDP were strongly correlated (r = 0.74 and r = 0.78; both p < 0.01). Further, the MP perfusion score and MP ventilation score, as well as QDP and VDP were strongly correlated (r = 0.88 and r = 0.86; both p < 0.01). MP-MRI detects abnormalities in lung perfusion and ventilation in patients with CF without intravenous or inhaled contrast agent application, and correlates strongly with the well-established CE perfusion MRI score and spirometry. Automated analysis of MP-MRI may serve as quantitative noninvasive outcome measure for diagnostic monitoring and clinical trials.

Dysarthria and dysphagia in patients with mitochondrial diseases

BackgroundInformation about dysarthria and dysphagia in mitochondrial diseases (MD) is scarce. However, this knowledge is needed to identify speech and swallowing problems early, to monitor the disease course, and to develop and offer optimal treatment and support. This study therefore aims to examine the prevalence and severity of dysarthria and dysphagia in patients with MD and its relation to clinical phenotype and disease severity. Secondary aim is to determine clinically relevant outcome measures for natural history studies and clinical trials. MethodsThis retrospective cross-sectional medical record study includes adults (age ≥ 18 years) diagnosed with genetically confirmed MD who participated in a multidisciplinary admission within the Radboud center for mitochondrial medicine between January 2015 and April 2023. Dysarthria and dysphagia were examined by administering the Radboud dysarthria assessment, swallowing speed, dysphagia limit, test of mastication and swallowing solids (TOMASS), and 6-min mastication test (6MMT). The disease severity was assessed using the Newcastle mitochondrial disease scale for adults (NMDAS). ResultsThe study included 224 patients with MD with a median age of 42 years of whom 37.5% were male. The pooled prevalence of dysarthria was 33.8% and of dysphagia 35%. Patients with MD showed a negative deviation from the norm on swallowing speed, TOMASS (total time) and the 6MMT. Furthermore, a significant moderate relation was found between the presence of dysarthria and the clinical phenotypes. There was a statistically significant difference in total time on the TOMASS between the clinical phenotypes. Finally, disease severity showed a significant moderate relation with the severity of dysarthria and a significant weak relation with the severity of dysphagia. ConclusionDysarthria and dysphagia occur in about one-third of patients with MD. It is important for treating physicians to pay attention to this subject because of the influence of both disorders on social participation and wellbeing. Referral to a speech and language therapist should therefore be considered, especially in patients with a more severe clinical phenotype. The swallowing speed, TOMASS and 6MMT are the most clinically relevant tests to administer.

P166 Utility of lung clearance index (LCI2.5) as an outcome measure in cystic fibrosis clinical trials – perspectives of people with cystic fibrosis and LCI2.5 operators

P166 Utility of lung clearance index (LCI2.5) as an outcome measure in cystic fibrosis clinical trials – perspectives of people with cystic fibrosis and LCI2.5 operators

Composite outcome measures in high-impact critical care randomised controlled trials: a systematic review

BackgroundThe use of composite outcome measures (COM) in clinical trials is increasing. Whilst their use is associated with benefits, several limitations have been highlighted and there is limited literature exploring their use within critical care. The primary aim of this study was to evaluate the use of COM in high-impact critical care trials, and compare study parameters (including sample size, statistical significance, and consistency of effect estimates) in trials using composite versus non-composite outcomes.MethodsA systematic review of 16 high-impact journals was conducted. Randomised controlled trials published between 2012 and 2022 reporting a patient important outcome and involving critical care patients, were included.Results8271 trials were screened, and 194 included. 39.1% of all trials used a COM and this increased over time. Of those using a COM, only 52.6% explicitly described the outcome as composite. The median number of components was 2 (IQR 2–3). Trials using a COM recruited fewer participants (409 (198.8–851.5) vs 584 (300–1566, p = 0.004), and their use was not associated with increased rates of statistical significance (19.7% vs 17.8%, p = 0.380). Predicted effect sizes were overestimated in all but 6 trials. For studies using a COM the effect estimates were consistent across all components in 43.4% of trials. 93% of COM included components that were not patient important.ConclusionsCOM are increasingly used in critical care trials; however effect estimates are frequently inconsistent across COM components confounding outcome interpretations. The use of COM was associated with smaller sample sizes, and no increased likelihood of statistically significant results. Many of the limitations inherent to the use of COM are relevant to critical care research.

American College of Rheumatology and Food and Drug Administration Summit: Summary of the Meeting, May 17-18, 2022.

The American College of Rheumatology and the US Food and Drug Administration co-sponsored a public meeting in May 2022 about challenges in the clinical development of drugs for rheumatoid arthritis (RA) and psoriatic arthritis (PsA), focusing on innovative clinical trial designs, outcome measures, and data collection methods. Recommendations include early dose-ranging studies and use of active comparators. Challenges and opportunities in assessing long-term safety by leveraging real-world data from electronic health records (EHRs) and claims data are discussed, along with insights from European registries and the evolving role of real-world evidence and artificial intelligence in regulatory evaluations. Endpoints for assessing disease activity and outcome measures used in RA and PsA trials are explored, emphasizing challenges in defining remission, assessing clinical response, and evaluating structural progression. The need for outcome measures that better reflect treatment targets and the potential of advanced imaging in future trials are highlighted. Challenges with placebo-controlled trials in RA are discussed and use of non-inferiority clinical trial design, in which new drugs are evaluated with active comparators, is proposed. Pragmatic trials in RA and PsA, employing decentralized approaches, are highlighted for their real-world relevance and administrative efficiencies. Strategies for identifying at-risk populations for RA and the challenges of using EHRs and insurance claims data in drug development are discussed. Registry data and digital health technologies show promise in bridging the gap between clinical trials and real-world effectiveness.

Quantitative muscle magnetic resonance imaging in limb-girdle muscular dystrophy type R1 (LGMDR1): A prospective longitudinal cohort study.

Limb-girdle muscular dystrophy (LGMD) type R1 (LGMDR1) is the most common subtype of LGMD in Europe. Prospective longitudinal data, including clinical assessments and new biomarkers such as quantitative magnetic resonance imaging (qMRI), are needed to evaluate the natural course of the disease and therapeutic options. We evaluated eight thigh and seven leg muscles of 13 LGMDR1 patients (seven females, mean age 36.7 years, body mass index 23.9 kg/m2) and 13 healthy age- and gender-matched controls in a prospective longitudinal design over 1 year. Clinical assessment included testing for muscle strength with quick motor function measure (QMFM), gait analysis and patient questionnaires (neuromuscular symptom score, activity limitation [ACTIVLIM]). MRI scans were performed on a 3-T MRI scanner, including a Dixon-based sequence, T2 mapping and diffusion tensor imaging. The qMRI values of fat fraction (FF), water T2 relaxation time (T2), fractional anisotropy, mean diffusivity, axial diffusivity and radial diffusivity were analysed. Within the clinical outcome measures, significant deterioration between baseline and follow-up was found for ACTIVLIM (p= 0.029), QMFM (p= 0.012). Analysis of qMRI parameters of the patient group revealed differences between time points for both FF and T2 when analysing all muscles (FF: p< 0.001; T2: p= 0.016). The highest increase of fat replacement was found in muscles with an FF of between 10% and 50% at baseline. T2 in muscles with low-fat replacement increased significantly. No significant differences were found for the diffusion metrics. Significant correlations between qMRI metrics and clinical assessments were found at baseline and follow-up, while only T2 changes in thigh muscles correlated with changes in ACTIVLIM over time (ρ = -0.621, p< 0.05). Clinical assessments can show deterioration of the general condition of LGMDR1 patients. qMRI measures can give additional information about underlying pathophysiology. Further research is needed to establish qMRI outcome measures for clinical trials.

The importance of including Long COVID outcomes when developing novel treatments for acute COVID-19.

The ongoing COVID-19 pandemic continues to present surges in infections demonstrating the persistent threat posed by COVID-19. Amidst efforts to develop effective treatments for acute COVID-19, there is a growing recognition of the need to address Long COVID. This manuscript reviews the current landscape of acute COVID-19 treatments and highlights the opportunity to incorporate Long COVID as a key outcome measure in clinical trials. Our analysis includes a review of current US clinical trials investigating acute COVID-19 treatments. Of the 19 studies that met our inclusion criteria, only one study currently incorporates Long COVID measurements. In our review, we argue there are 7 compelling reasons to include Long Covid measurements, including: (1) Long COVID is not rare (2) Long COVID is debilitating to individuals and has a high societal cost (3) Those at high risk of severe COVID-19 are also at higher risk of developing Long COVID if they are infected with COVID-19 (4) Treatments for acute COVID-19 may reduce the risk of Long COVID (5) Measures exist to track Long COVID (6) Long COVID considerations are potentially important for acute COVID-19 treatment decision-making (7) Deaths and hospitalizations due to COVID-19 are increasingly rare, creating an opportunity for other important clinical endpoints to be considered In conclusion, while not every trial needs to include assessments of Long COVID, it is worth the research burden to include assessments where possible as this could facilitate the uptake of acute COVID-19 treatments that lessen the societal burden of Long COVID.

Application of Patient-Reported Outcome Measurements in Adult Tumor Clinical Trials in China: Cross-Sectional Study.

International health policies and researchers have emphasized the value of evaluating patient-reported outcomes (PROs) in clinical studies. However, the characteristics of PROs in adult tumor clinical trials in China remain insufficiently elucidated. This study aims to assess the application and characteristics of PRO instruments as primary or secondary outcomes in adult randomized clinical trials related to tumors in China. This cross-sectional study identified tumor-focused randomized clinical trials conducted in China between January 1, 2010, and June 30, 2022. The ClinicalTrials.gov database and the Chinese Clinical Trial Registry were selected as the databases. Trials were classified into four groups based on the use of PRO instruments: (1) trials listing PRO instruments as primary outcomes, (2) trials listing PRO instruments as secondary outcomes, (3) trials listing PRO instruments as coprimary outcomes, and (4) trials without any mention of PRO instruments. Pertinent data, including study phase, settings, geographic regions, centers, participant demographics (age and sex), funding sources, intervention types, target diseases, and the names of PRO instruments, were extracted from these trials. The target diseases involved in the trials were grouped according to the American Joint Committee on Cancer Staging Manual, 8th Edition. Among the 6445 trials examined, 2390 (37.08%) incorporated PRO instruments as part of their outcomes. Within this subset, 26.82% (641/2390) listed PRO instruments as primary outcomes, 52.72% (1260/2390) as secondary outcomes, and 20.46% (489/2390) as coprimary outcomes. Among the 2,155,306 participants included in these trials, PRO instruments were used to collect data from 613,648 (28.47%) patients as primary or secondary outcomes and from 74,287 (3.45%) patients as coprimary outcomes. The most common conditions explicitly using specified PRO instruments included thorax tumors (217/1280, 16.95%), breast tumors (176/1280, 13.75%), and lower gastrointestinal tract tumors (173/1280, 13.52%). Frequently used PRO instruments included the European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire-30, the visual analog scale, the numeric rating scale, the Traditional Chinese Medicine Symptom Scale, and the Pittsburgh Sleep Quality Index. Over recent years, the incorporation of PROs has demonstrated an upward trajectory in adult randomized clinical trials on tumors in China. Nonetheless, the infrequent measurement of the patient's voice remains noteworthy. Disease-specific PRO instruments should be more effectively incorporated into various tumor disease categories in clinical trials, and there is room for improvement in the inclusion of PRO instruments as clinical trial end points.