Summary Objective To develop the conceptual framework for an MLTC-specific patient-reported outcome measure (PROM), the Symptom Burden Questionnaire™ for MLTC (SBQ™-MLTC). Design Mixed-methods study: (1) symptom list generation; (2) assessment of list face validity; and (3) construction of a conceptual framework. Setting Concept elicitation and conceptual framework development using existing PROMs identified through the Mapi Research Trust PROQOLID eCOA database and AI-generated symptom lists. Participants Fifty-one condition-specific PROMs with evidence of patient involvement during concept elicitation were included for symptom extraction. ChatGPT-4 generated symptom lists for 24 conditions prevalent in MLTC. Seventeen healthcare practitioners reviewed symptom relevance and contributed to refinement of the conceptual framework. Main outcome measures Identification, refinement, and organisation of relevant MLTC symptoms into body system and functional domains, and development of the SBQ™-MLTC's conceptual framework. Results ePROVIDE searches in July and August 2023 identified 51 condition-specific PROMs for 24 conditions prevalent in MLTC. ChatGPT-4 was prompted to generate a list of 75 symptoms for each condition. A merged list of 2202 symptoms was iteratively reduced to 190 symptoms for healthcare practitioner review. The final conceptual framework included 151 symptoms spanning 18 body system and functional domains. Conclusions This study represents the first phase in the development of an MLTC-specific PROM of symptom burden. Generative AI output triangulated with content from existing PROMs and healthcare practitioner review proved a feasible approach to concept elicitation. Planned cognitive debriefing will confirm content validity of the SBQ™-MLTC for people with lived experience. In the future, the SBQ™-MLTC could support integrated, symptom-led approaches for clinical management of MLTC.

Background: The high prevalence of long COVID globally necessitates investigation into its self-management, especially given the absence of definitive and effective treatments and uneven access to healthcare services. Methods: This study surveyed the use of over-the-counter (OTC) medicines, supplements, remedies, and other non-prescription therapies for managing long COVID symptoms in the UK. It aimed to identify the range of treatments used for self-management, explore the sources of these treatments, factors influencing treatment choices, and associated out-of-pocket expenses. A cross-sectional electronic survey was provided to individuals experiencing long COVID. It included questions on the use of OTC medications, supplements, and other therapies, where they were sourced, decision-making influences, and financial costs. Descriptive statistics and thematic analysis were applied to analyse the data. Results: Among the 193 surveyed participants, significant use of vitamins, minerals, and herbal treatments (88.8%), and analgesics (73.6%) was reported, with 42% exceeding recommended dosages. Some participants sought relief through alternative therapies such as physiotherapy and acupuncture, often incurring significant personal expenses. Choices about self-management were influenced by medical professionals, family, friends, and online sources, including support groups and social media. Conclusions: People with long COVID may access a wide range of OTC medicines, dietary supplements, herbal remedies, and non-pharmacological therapies to self-manage symptoms. Healthcare providers should be aware of the use of non-prescribed therapies among long COVID sufferers and consider these in their treatment plans. Public health policies should focus on providing accurate information and guidance for patients self-managing long COVID symptoms.

There is widespread interest among patients, clinicians, regulators and other constituents in post-treatment patient-reported cancer data. Side effect bother is a patient-reported outcome (PRO) that can capture an important aspect of tolerability. In this study, we examined side effect bother at cancer treatment discontinuation and post-discontinuation in commercial cancer trials. We sought to understand completion rates, the extent of bother and its association with other PROs. Data were evaluated from three trials in patients with solid tumours (renal cell carcinoma and breast cancer). Side effect bother was measured with the Functional Assessment of Chronic Illness Therapy (FACIT) GP5 item. Symptom items were drawn from FACIT and function items were drawn from the EQ-5D-3L. FACIT items, including the GP5, are on a 0–4 scale (higher = worse symptoms/bother), and were dichotomised as 0–1 (“low”) vs 2–4 (“moderate”). EQ-5D-3L items were characterised as no problems (1) and some problems (2–3). Descriptive and correlation analyses were conducted separately for each trial. Among patients who received treatment, completion rates at discontinuation for most items were at least 70

Patient-reported outcomes can provide valuable evidence on the efficacy and tolerability of treatments throughout the drug development pipeline supporting regulatory decision-making, reimbursement and patient-centred care. Use of international guidelines and tools can optimise assessment and data quality and maximise impact. Calvert et al. highlight how patient-reported outcomes (PROs) provide critical evidence for drug regulation, reimbursement, and clinical care. They advocate for using international guidelines and tools to enhance data quality and maximize the impact of these data to support decision-making and patient-centred care.

To describe the humanistic burden and economic impact among informal caregivers of individuals with sickle cell disease (SCD) and recurrent vaso-occlusive (VOCs) across North America and Europe. A mixed-methods study was conducted with qualitative interviews in the US and UK and an online survey in the US, Canada, UK, France, Germany, Italy, Spain, and the Netherlands. The survey included CarerQoL-7D, WPAI:CG, and explored time spent providing informal care, out-of-pocket expenses, and health inequity. Interviews were analyzed using the Framework Method and survey data with descriptive analyses. Monetary values were standardized to US dollars. Interviews with 10 caregivers identified five key themes: (1) Need for a strong support network; (2) Providing constant care/attention; (3) Ensuring optimal care; (4) Major lifestyle adjustments; and (5) Impact on caregiver’s emotional and physical wellbeing. 173 caregivers completed the survey. The CarerQoL indicated adverse impacts on health-related quality of life (HRQoL) with > 70

To describe the humanistic and economic burden among informal caregivers of individuals with transfusion-dependent β-thalassemia (TDT) across the US and Europe. A mixed-methods study was conducted with qualitative interviews in the US and UK and an online survey in the US, UK, France, Italy, and the Netherlands. The survey included CarerQoL-7D, ZBI-12, and WPAI: CG and captured time spent providing informal care and out-of-pocket (OOP) expenses. Interviews were analyzed using the Framework Method, and survey data with descriptive analyses. Monetary values were standardized to US dollars (2025 USD). Interviews with 10 caregivers revealed five key themes: (1) Need for a strong support network; (2) Burden of disease management and constant care; (3) Barriers and facilitators to optimal care; (4) Impact on caregivers’ daily life, work, and aspirations; and (5) Emotional distress and impacts on well-being. Seventy caregivers completed the survey. The CarerQoL-7D indicated adverse impacts on quality of life (QoL), with > 60

BACKGROUND:There is growing recognition of the importance of patient-reported tolerability in complementing traditional clinician-reported safety evaluation of cancer therapies. Recent regulatory guidance listed the evaluation of overall side effect impact as a core patient-reported outcome in oncology clinical trials. A single item ('GP5') that asks about side effect bother is included in the Functional Assessment of Chronic Illness Therapy and has been used to capture overall side effect impact. This paper sought to expand the evidence base for GP5 by examining its association with clinician-reported treatment-emergent adverse events and patient-reported global health. METHODS:We examined six commercial cancer clinical trials that collected GP5. The patient population was drawn from the safety population and the analysis focused on the first on-treatment assessment. Clinician-reported adverse events were classified as symptomatic if such adverse events were considered amenable to patient self-reporting (e.g. nausea). Chi-square tests and Pearson's correlation were used to examine associations. We considered adverse event grade and frequency, both for symptomatic adverse events and any type of adverse events. Global health was measured using the visual analogue scale of the EuroQol-5 Dimensions-3 Levels measure. 'Moderate-severe' bother was characterised as scores of 2-4 on a 0-4 point scale for GP5, and 'severe' bother was characterised as scores of 3-4. Analyses were conducted separately for each trial. RESULTS:Data from 3,557 patients were included. Across the trials, most (71.7%-94.2%) patients had an adverse event of some kind, but fewer (17.1%-44.4%) had an adverse event of grade 3 or higher. In general, fewer than 50% of patients (20.6%-44.2%) reported moderate-severe bother and 5.8%-17.% reported severe bother. There were consistent, albeit not always statistically significant, associations between GP5 and adverse events, and GP5/global health correlations ranged from -0.17 to -0.41. DISCUSSION:GP5 is associated with both clinician- and patient-reported symptoms, suggesting its validity and usefulness as part of comprehensive tolerability assessment of cancer trials.

Abstract Objectives To explore methods for collection, reporting and analysis of patient-reported outcome (PRO) data in health technology assessment (HTA) in England, France, and Germany, and understand the impact and challenges associated with using PRO data in HTA. Methods A targeted literature review (TLR) was conducted in November 2023 to identify PRO-related data specifications for HTA in European markets and inform an interview discussion guide. Qualitative, semi-structured 60-minute interviews with key opinion leaders (KOLs) with HTA- and PRO-related expertise in England, France and Germany were conducted to gain expert perspectives on PRO and HTA practices, and to identify opportunities for HTA harmonization across European markets. The interview transcripts were analyzed using content analysis methods and key results extracted by a single analyst into Microsoft® Excel. Results KOLs from England (n = 4), France (n = 3) and Germany (n = 5) were interviewed. Availability of guidance on PRO data collection, analysis and reporting in HTA varies between the HTA bodies included. Guidance, where available, is country specific, and therefore lacks harmonization across included markets. In terms of the perceived impact of PRO data on HTA decision making, KOLs from Germany gave a high rating, while KOLs from England and France gave ratings of low to high impact and moderate to high impact, respectively. It was reported by KOLs in all markets that PROs are expected for submissions in highly symptomatic and burdensome conditions, and that the relative importance of PRO to HTA outcomes varies by disease. KOLs cited challenges with using PRO data in HTA. Commonly cited challenges were related to methodological considerations and included: ‘no/suboptimal PRO data collection/submission (e.g., due to value perceptions)’ and ‘selected instruments not fit-for-purpose/PRO benefits not adequately represented in models’. Adding to the challenges with using PRO data in HTA, there are inconsistencies between Joint Clinical Assessment (JCA) guidance and PRO data requirements for HTA in included markets. Conclusions There is a lack of transparency and harmonization in terms of the requirements for PRO data collection, analysis and reporting for HTA in England, Germany and France. Enhanced transparency of HTA requirements will facilitate harmonization efforts and may be supported by JCA.

Epidemiological research studies into Long Covid, currently defined by prolonged symptoms after SARS-CoV-2 infection, have reported widely varying prevalence estimates. As well as rapidly evolving scientific knowledge of Long Covid, these differences are partly driven by substantial methodological heterogeneity between studies, including the outcome definition of Long Covid; duration of follow-up; study design, period and population; sampling frame; data source; and the statistical techniques employed. Having a robust understanding of the prevalence of and risk factors for Long Covid is essential for informing treatment pathways, service provision and policy decisions. In preparation for the public health response to future epidemics and pandemics, this review outlines key epidemiological and statistical considerations and recommendations when designing studies of emerging post-acute infection syndromes, focussing on Long Covid as a case study.

Advanced therapy medicinal products (ATMPs) are increasingly evaluated in early-phase clinical trials, where understanding patient-reported symptoms, tolerability, and health-related quality of life is critical. Electronic patient-reported outcome (ePRO) systems offer potential advantages over paper-based methods, but evidence on their feasibility and acceptability in ATMP trials remains limited. To assess the feasibility and acceptability of the PROmics ePRO system when deployed within a phase II, multi-disease ATMP clinical trial involving patients with immune-mediated inflammatory diseases. A qualitative interview-based feasibility study was embedded within the POLARISE trial, a multicentre phase II ATMP basket trial investigating ORBCEL-C™ in patients with rheumatoid arthritis, primary sclerosing cholangitis, Crohn’s disease, and lupus nephritis. Semi-structured interviews were conducted with trial participants and research and clinical staff who used the PROmics system. Interviews explored experiences of training, usability, questionnaire burden, real-time alerts, and integration within trial workflows. Transcripts were thematically analysed using the framework method. Fourteen participants were interviewed (seven patients and seven staff). Overall, the PROmics system was perceived as acceptable, intuitive, and easy to use by both patients and staff. Automated reminders and real-time alerts were key facilitators of engagement and provided reassurance to patients that their symptoms were actively monitored. However, several feasibility challenges were identified, including technical issues, uncertainty around support pathways, questionnaire burden, and the workload associated with managing alerts. Staff turnover and limitations in clinical dashboard usability and system integration further increased implementation burden. The PROmics ePRO system was acceptable and valued by patients and staff in the context of an ATMP trial, but successful implementation requires careful attention to technical stability, user support, questionnaire scheduling, and alert management within existing trial infrastructure. Addressing these issues is essential to maximise the feasibility, sustainability, and value of digital PROM collection in future ATMP clinical trials. n/a RR2-10.1136/bmjopen-2022-063199

Objectives Patient-reported outcomes (PROs) are essential for understanding how cancer treatments affect individuals’ symptoms, daily functioning and quality of life. This study examined how PRO data from pivotal clinical trials in breast cancer (BC), gastrointestinal (GI) cancers and non-small cell lung cancer (NSCLC) are reflected in regulatory drug labels and public-facing communications such as American Society of Clinical Oncology daily news. The goal was to identify gaps in the communication of these data, particularly in formats accessible to non-technical audiences and to highlight opportunities for improvement.Methods and analysis We conducted a targeted review of oncology drugs approved between 2014 and 2024 by the US Food and Drug Administration and the European Medicines Agency. For each product, we assessed pivotal trials for PRO endpoints and reviewed regulatory labels for PRO claims. Public-facing materials—including sponsor websites, medical society platforms and patient advocacy content—were evaluated for the presence, clarity and visibility of PRO messaging. Messaging strength was internally rated as low, medium or high.Results Among 128 pivotal trials (28 BC, 34 GI, 66 NSCLC), 105 (82%) included PROs—84 as secondary and 40 as exploratory endpoints. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item (EORTC QLQ-C30) was used in 83 trials (79.0%), and EuroQol Group in 72 (68.6%). Only 10 products included PRO content in their regulatory labelling. Of 16 BC drugs, all had PRO data, but only 4 had regulatory PRO claims. Most sponsor websites lacked PRO content; only seven products across all indications included healthcare professional-facing PRO narratives and only two on patient-facing websites. No product achieved a high messaging strength rating; 53 of 64 rated products were categorised as low (limited or no PRO communication).Conclusions Despite widespread PRO data collection, integration into labelling and public communication remains limited. While label inclusion supports compliant dissemination, some PRO findings appear in public materials without formal claims. Advancing both methodological rigour and clear regulatory guidance is essential to promote balanced, patient-relevant communication in oncology.

STUDY OBJECTIVE:Patient-reported outcome measures (PROMs) provide valuable data to inform regulatory decision making, health technology assessment and routine clinical care. We aimed to develop a feasibility item checklist for PROMs and their selection, beyond their psychometric properties (FACTOR3). METHODS:We followed a five-stage method to select parameters for PROM evaluation. 1) A scoping literature review identified candidate items for consideration; 2) round 1 modified Delphi was used to select items for inclusion or exclusion, conducted by the design group (n = 14); 3) feedback on the checklist was provided by representatives from the European Medicines Agency and National Institute for Health and Care Excellence; 4) round 2 modified Delphi was used to finalise item selection, conducted by the clinical domains group (n = 21) and 5) evaluation of the feasibility item checklist using a selection of PROMS (EQ5D-5L, HeartQOL, the Oxford Hip Score, The EORTC Core Questionnaire QLQ-C30, Re-QOL-10 and NEI-VFQ-25) (Fig. 1). RESULTS:The scoping review identified 13 items relating to the intrinsic feasibility of using PROMs which were considered in the modified Delphi. The final FACTOR3 checklist included eight unique candidate items: price; licensing, comprehensibility, duration, coverage, translations, electronic device compatibility; and minimal important difference. Of the six PROMS evaluated, the intraclass correlation coefficient was 0.81, suggesting good reliability. CONCLUSIONS:FACTOR3 is a feasibility item checklist to assess the implementation characteristics of PROMs in research, regulation and routine clinical care. It may be used in conjunction with existing psychometric evaluation and user guides for PROMS to facilitate their use in health care.

Transparent and accurate reporting in early phase dose-finding (EPDF) clinical trials is crucial for informing subsequent larger trials. The SPIRIT statement, designed for trial protocol content, does not adequately cover the distinctive features of EPDF trials. Recent findings indicate that the protocol contents in past EPDF trials frequently lacked completeness and clarity. To address this gap, the international consensus-driven SPIRIT-DEFINE checklist was developed through a robust methodological framework for guideline development, with the aim to improve completeness and clarity in EPDF trial protocols. The checklist builds on the SPIRIT statement, adding 17 new items and modifying 15 existing ones.The SPIRIT-DEFINE explanation and elaboration (E&E) document provides comprehensive information to enhance understanding and usability of the SPIRIT-DEFINE checklist when writing an EPDF trial protocol. Each new or modified checklist item is accompanied by a detailed description, its rationale with supportive evidence, and examples of good reporting curated from EPDF trial protocols covering a range of therapeutic areas and interventions. We recommend utilising this paper alongside the SPIRIT statement, and any relevant extensions, to enhance the development and review of EPDF trial protocols.By facilitating adoption of the SPIRIT-DEFINE statement for EPDF trials, this E&E document can promote enhancement of methodological rigour, patient safety, transparency, and facilitate the generation of high-quality, reproducible evidence that will strengthen the foundation of early phase research and ultimately improve patient outcomes. Funding This work is a further extension of the SPIRIT-DEFINE study, which obtained no external funding. The principal investigator (CY) used internal staff resources, together with additional resources from external partners, to conduct this study. The SPIRIT-DEFINE study is a component of the DEFINE project, which also developed the MRC/NIHR funded CONSORT-DEFINE guidance. ICR-CTSU receives programmatic infrastructure funding from Cancer Research UK (C1491/A25351; CTUQQR-Dec22/100004), which has contributed to accelerating the advancement and successful completion of this work.

The global evidence on the risk of symptoms of Long Covid in general populations infected with SARS-CoV-2 compared to uninfected comparator/control populations remains unknown. We conducted a systematic literature search using multiple electronic databases from January 1, 2022, to August 1, 2024. Included studies had ≥100 people with confirmed or self-reported COVID-19 at ≥28 days following infection onset, and an uninfected comparator/control group. Results were summarised descriptively and meta-analyses were conducted to derive pooled risk ratio estimates. 50 studies totaling 14,661,595 people were included. In all populations combined, there was an increased risk of a wide range of 39 out of 40 symptoms in those infected with SARS‑CoV‑2 compared to uninfected controls. The symptoms with the highest pooled relative risks were loss of smell (RR 4.31; 95% CI 2.66, 6.99), loss of taste (RR 3.71; 95% CI 2.22, 7.26), poor concentration (RR 2.68; 95% CI 1.66, 4.33), impaired memory (RR 2.53; 95% CI 1.82, 3.52), and hair loss/alopecia (RR 2.38; 95% CI 1.69, 3.33). This evidence synthesis, of 50 controlled studies with a cumulative participant count exceeding 14 million people, highlights a significant risk of diverse long-term symptoms in individuals infected with SARS-CoV-2, especially among those who were hospitalised.