Patient-reported outcomes in NAFLD/NASH clinical trials: A blind spot that needs addressing.
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ABSTRACT:
SUBMITTER: Sena E
PROVIDER: S-EPMC9758425 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
Publications
Patient-reported outcomes in NAFLD/NASH clinical trials: A blind spot that needs addressing.
Sena Elena E Manzano-Nunez Ramiro R Rivera-Esteban Jesus J Pericas Juan M JM
JHEP reports : innovation in hepatology 20220922 1
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Project description:To optimize the use of patient-reported outcomes (PROs) in clinical research, it is first necessary to review the current use of these outcomes in clinical trials to determine under what circumstances they are most useful, and to reveal current limitations.To investigate current patterns of use of PROs in clinical trials.We conducted a systematic literature review of all double-blind, placebo-controlled, randomized clinical trials using one or more PROs as a study outcome from 2004 to 2006. Data were abstracted and analyzed with descriptive statistics and logistic regression to characterize the use of PROs in clinical trials.The 180 clinical trials that met the study inclusion criteria used 173 unique instruments to measure a total of 466 PROs. Most PRO measurements were obtained using relatively few PRO instruments, with one-third of PRO instruments applied in more than 1 trial. In multivariable analysis, tests of statistical significance were more often reported for PROs used as primary trial outcomes. Statistically significant PRO outcomes (P<0.05) were more likely among disease-specific PROs compared with general PROs, PROs with a discussion of minimally important difference, and larger trials.PRO instruments may be improved through efforts to provide centralized electronic administration, cross-validation, and standardized interpretation of clinically relevant outcomes. The majority of PROs used in current clinical trials come from relatively few, commonly used disease-specific PRO instruments within major therapeutic areas.
| S-EPMC3682647 | biostudies-literature
Project description:IntroductionQuantitative patient-reported outcome (PRO) measures ideally are analyzed on their original scales and responder analyses are used to aid the interpretation of those primary analyses. As stated in the FDA PRO Guidance for Medical Product Development (2009), one way to lend meaning and interpretation to such a PRO measure is to dichotomize between values where within-patient changes are considered clinically important and those that are not. But even a PRO scale with a cutoff score that discriminates well between responder and non-responders is fraught with some misclassification.MethodsUsing estimates of sensitivity and specificity on classification of responder status from a PRO instrument, formulas are provided to correct for such responder misclassification under the assumption of no treatment misclassification. Two case studies from sexual medicine illustrate the methodology.ResultsAdjustment formulas on cell counts for responder misclassification are a direct extension of correction formulas for misclassification on disease from a two-way cross-classification table of disease (yes, no) and exposure (yes, no). Unadjusted and adjusted estimates of treatment effect are compared in terms of odds ratio, response ratio, and response difference. In the two case studies, there was considerable underestimation of treatment effect.Discussion and conclusionsThe methodology can be applied to different therapeutic areas. Limitations of the methodology, such as when adjusted cell estimates become negative, are highlighted. The role of anchor-based methodology is discussed for obtaining estimates of sensitivity and specificity on responder classification. Correction for treatment effect bias from misclassification of responder status on PRO measures can lead to more trustworthy interpretation and effective decision-making. Clinicaltrials.gov: NCT00343200.
| S-EPMC8332587 | biostudies-literature
Project description:Patient-reported outcomes (PROs) are reports of a person's health status that provide a global perspective of patient well-being. PROs can be classified into 4 primary domains: global, mental, physical, and social health. In this descriptive review, we focus on how PROs can be used in cardiac clinical trials, with an emphasis on cardiac surgical trials for patients with coronary heart disease and heart failure. We also highlight ongoing challenges and provide specific suggestions and novel opportunities to advance cardiac clinical trials. Current challenges include the long-term measurement of PROs in clinical trials beyond 1 year, inconsistency in the choice of the outcome measures among studies, and the lack of measurement of PROs across multiple domains. Opportunities for advancement include measuring PROs using consumer health informatics tools, including returning information back to participants in formats that they can understand using visualization. Future opportunities include quantifying cohort-specific minimal clinically important differences for PROs.
| S-EPMC8487900 | biostudies-literature
Project description:Global prevalence of non-alcoholic fatty liver disease (NAFLD) has been growing in the last decades, especially in western countries, due to increased prevalence of diabetes, obesity or other components of metabolic syndrome. NAFLD recently became an important cause of hepatocellular carcinoma (HCC), even in non-cirrhotic patients. Patients with HCC-NAFLD are usually older, with more morbidities (especially cardiovascular diseases and metabolic disorders) and have advanced disease at the diagnosis due to the absence of surveillance, which is considered not cost-effective in patients without advanced fibrosis/cirrhosis, given the large prevalence of NAFLD in the general population. For these reasons, patients with HCC-NAFLD unlikely underwent curative treatments, and have been reported to have lower overall survival (OS) compared to individuals with HCC related to other aetiologies. However, this difference is not confirmed by data of patient subgroups who received curative treatment. In our review, we selected studies published over the past 8 years that analyse characteristics and outcomes of HCC-NAFLD patients who underwent surgery with the aim of identifying features that could predict outcomes and potential selection criteria. All the studies confirm that patients with HCC-NAFLD are older, with many comorbidities and that HCC occurs frequently even in non-cirrhotic livers. There is no agreement about intraoperative and perioperative complications. Regarding outcomes, all papers agree that patients with HCC in NAFLD who undergo surgery have a better OS compared to other aetiologies. Summarizing, surgery is a good curative option for patients with HCC-NAFLD, perhaps even better than transplantation in terms of OS. In this group of patients, it seems to be essential to evaluate cardio-pulmonary and general operative risk, in addition to the normal risk assessment related to liver function to avoid an underestimation, especially for patients without severe underlying fibrosis.
| S-EPMC7398743 | biostudies-literature
Project description:(1) The study evaluated correlations between multi-frequency vibrometry (MF-V) and the measure of chemotherapy-induced peripheral neuropathy developed by the European Organization for the Research and Treatment of Cancer (CIPN18). (2) Patients with cancer scheduled to undergo treatment with capecitabine and oxaliplatin (CAPOX) or carboplatin and paclitaxel (Carbo-Tax) were recruited in a prospective, observational study with MF-V and the CIPN18 from baseline to one year after end of treatment. (3) The study recruited 31 evaluable patients. All MF-V measurements correlated significantly with the CIPN18 scores (r = 0.25−0.48, p > 0.003), with a low frequency (32 Hz) from metatarsals showing the best correlation coefficients (0.059 Z-score per CIPN18 point change, r = 0.48, CI-95 = [0.32; 0.60], p > 0.0001). The largest change in MF-V scores from baseline was seen in low-frequency VPTs taken from metatarsals at 8 Hz three months after end of treatment (from −0.26, CI-95 [−0.85, 0.38] to 1.15, CI-95 [0.53, 1.84]) for patients treated with oxaliplatin and at 32 Hz one year after end of treatment (from 0.09, CI-95 [−0.56, 0.77] to 0.88, CI-95 [0.34, 1.47]) for patients treated with paclitaxel. (4) Low-frequency vibration perception thresholds (8 and 32 Hz) correlated better with CIPN18 scores than high-frequency ones (128 and 250 Hz). If validated, this finding will advance CIPN pathophysiological understanding and inform the development of assessment methods.
| S-EPMC8999713 | biostudies-literature
Project description:Background: Non-alcoholic steatohepatitis (NASH) is a chronic liver disease with severe complications and without approved therapies. Currently, there is limited data on the overall burden of the disease for patients or on patient needs and preferences. This study investigates patient preferences in relation to potential future therapies for NASH. In addition, the factors that are relevant to patients and their importance in relation to future treatment options are explored. Method: Telephone in-depth interviews (TDIs) preceded an online 30-min quantitative survey. The online survey included (1) multiple choice questions (MCQs) on NASH diagnosis and disease background. (2) An exercise to determine patients' satisfaction levels with information provided at diagnosis, and to explore symptomatology in detail. (3) Exercises to evaluate potential new products and product attributes, including a "drag and drop" ranking exercise, and an adaptive choice-based conjoint exercise (ACBC). (4) The EQ-5D-5L questionnaire and the Visual Analog Scale (VAS), which measures patients' health status. (5) Collection of socio-demographic data, and (6) Questions to measure patient satisfaction with the survey. Results: There were 166 patients included in this study from Canada [n = 36], Germany [n = 50], the UK [n = 30], and USA [n = 50]. Fifty seven percent of patients [n = 94] had had a liver biopsy for confirmation of NASH. Patients were often unable to link their symptoms to NASH or other conditions. ACBC results showed that efficacy, defined as "impact on liver status" was the single most important attribute of a potential future NASH therapy. Other attributes considered to have secondary importance included impact on weight, symptom control and the presence of side effects. The EQ-5D utility score was 0.81 and VAS = 67.2. Conclusion: "Impact on liver status" is the primary outcome sought. Patients demonstrate a general lack of understanding of their disease and appeared to be unfamiliar with longer-term consequences of NASH. It is necessary to improve patient understanding of NASH and its progressive nature, and there is a need for improving confirmatory diagnosis and monitoring.
| S-EPMC6457207 | biostudies-literature
Project description:BackgroundLymphoma treatment can lead to long-term consequences such as fatigue, infertility and organ damage. In clinical trials, survival outcomes, clinical response and toxicity are extensively reported while the assessment of treatment on quality of life (QoL) and symptoms is often lacking.ObjectiveWe evaluated the use and frequency of patient-reported outcome (PRO) instruments used in randomized controlled trials (RCTs) for Hodgkin lymphoma (HL) and their consistency of reporting.MethodsMEDLINE, CENTRAL and trial registries for RCTs investigating HL were systematically searched from 01/01/2016 to 31/05/2022. Following trial selection, trial, patient characteristics and outcome data on the use of PRO measures (PROMs) and reporting of PROs using a pre-defined extraction form were extracted. To assess reporting consistency, trial registries, protocols and publications were compared.ResultsWe identified 4,222 records. Following screening, a total of 317 reports were eligible for full-text evaluation. One hundred sixty-six reports of 51 ongoing/completed trials were included, of which 41% of trials were completed and 49% were ongoing based on registry entries. Full-text or abstract were available for 33 trials. Seventy percent of trials were conducted in the newly diagnosed disease setting, the majority with advanced HL. In 32 trials with published follow-up data, the median follow-up was 5.2 years. Eighteen (35%) completed/ongoing trials had mentioned PRO assessment in registry entries, protocol or publications. Twelve trials (67%) had published results and only 6 trials (50%) reported on PROs in part with the exception of 1 trial where PROs were evaluated as secondary/exploratory outcome. The most referenced global PROM was the EORTC-QLQ-C30 (12 studies), the EQ-5D (3 studies) and the FACT-Neurotoxicity (3 studies). FACT-Lymphoma, a disease-specific PROM for non-HL was mentioned in one ongoing trial. None of the trials referenced the EORTC QLQ-HL27, another disease-specific PROM developed specifically for HL patient's QoL assessment.DiscussionsOnly one-third of RCTs in HL report PROs as an outcome and only half present the outcome in subsequent publications, showcasing the underreporting of PROs in trials. Disease-specific PROMs are underutilized in the assessment of QoL in HL patients. Guidance on the assessment of PROs is needed to inform on comprehensive outcomes important to patients.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=391552, identifier CRD42023391552.
| S-EPMC10965683 | biostudies-literature
Project description: Not available
| S-EPMC5362349 | biostudies-literature
Project description:Investigators of clinical trials in which the list of outcomes include patient-reported outcomes (PROs) - usually labeled quality of life (QoL) - have a large number of instruments from which to choose. The extent and manner in which PRO instruments are used in clinical trials can be assessed using data from clinical trial registries. Most medical journals now require a clinical trial be registered before its results are considered for publication. This requirement is intended to discourage publication bias, such as the reporting of tests of hypotheses different from those stipulated at the start of the trial and selective reporting of partial results.To assess the usage of PRO instruments in registered trials by various trial characteristics and to determine if the instruments are adequately identified in the registry.A local copy of the ClinicalTrials.gov database was made in September 2007. The outcomes of all interventional trials registered since September 2004 were assessed for usage of a PRO instrument. Odds ratios of PRO usage were estimated by a logistic regression model.Of 17,704 interventional trials, 2481 (14.0%) used at least one PRO instrument. However, less than half of those trials (41.0%) identified the instrument to be used. PRO usage is positively associated with phase (III), randomization type (randomized), intervention type (behavior) and sponsorship type (university/research organization).PRO instruments are used in a significant percentage but minority of clinical trials. Trial registries should require that all PRO instruments be identified, including the concepts or outcomes they are intended to measure.
| S-EPMC2683916 | biostudies-other
Project description:BackgroundSymptoms are common among patients enrolled in phase I trials. We assessed the validity of Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) items in relation to previously validated assessments of quality of life and psychological distress. We used data from a randomized trial testing a palliative care support intervention for patients enrolled on phase I trials.MethodsPatients (n = 479) were accrued to the parent study prior to initiating a phase I clinical trial with data collected at baseline, 4, and 12 weeks. We determined the correlation of PRO-CTCAE with distress level, Functional Assessment of Cancer Therapy - General (FACT-G) total, and subscale domain scores.ResultsPatients were predominantly female (56.8%) and older than age 60 years, and 30.7% were from minority populations. The correlation coefficient for distress level for all PRO-CTCAE items was small to moderate (Pearson r = 0.33-0.46). Pearson correlation coefficient for FACT-G total was moderate (r = -0.45 to -0.69). Stronger associations were noted for mood items of the PRO-CTCAE only (with distress level, r = 0.55-0.6; with FACT-G, r = -0.54 to -0.6). PRO-CTCAE symptom interference scores had the strongest correlation with distress level (Pearson r = 0.46) and FACT-G total (Pearson r = -0.69). Correlations between PRO-CTCAE items and corresponding FACT-G (total and subscales) and distress levels reached statistical significance for all items (P <.001).ConclusionEvidence demonstrates validity of PRO-CTCAE in a heterogeneous US sample of patients undergoing cancer treatment on phase I trials, with small to moderate correlations with distress level for all PRO-CTCAE items and moderate correlations with quality of life as measured by FACT-G total.
| S-EPMC7768928 | biostudies-literature