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Jennifer Dine,1 Yanfen Guan,2 Mirline Milien,1 Claire Ervin,1 Dana D Byrne,2 Michelle L Brown,2 Carisa De Anda,2 Josephine M Norquist2 1RTI Health Solutions, Research Triangle Park, Durham, NC, USA; 2Merck & Co., Inc., Rahway, NJ, USACorrespondence: Jennifer Dine, Patient-Centered Outcomes Assessment, RTI Health Solutions, 3040 E Cornwallis Road, Research Triangle Park, Durham, NC, 27709, USA, Email jdine@rti.orgIntroduction: The COVID-19 Symptoms Daily Diary (CSDD) is a patient-reported outcome measure designed to assess the severity of core COVID-19 symptoms in clinical trials. The preliminary version of the CSDD was developed based on regulatory guidance and the hallmark COVID-19 symptoms identified by the CDC. This study aimed to evaluate CSDD content validity, to determine whether it is fit for the purpose of supporting efficacy endpoints in clinical trials of treatments for COVID-19. This research also sought to evaluate the appropriateness of a newly developed Pre–COVID-19 Symptoms Questionnaire.Methods: A targeted literature review was completed to evaluate the relevance of concepts included in the diary and to identify any important symptoms that may have been missing. Hybrid (concept elicitation and cognitive debriefing) semistructured qualitative interviews were then conducted across 3 iterative rounds with 30 adults in the United States recently diagnosed with COVID-19.Results: The CSDD included concepts that were most frequently reported by interview participants, including those identified as most bothersome and most important to treat. During cognitive debriefing, participants described the diary concepts as salient and reported the instructions, recall period, and response options as clear and appropriate. Only 2 of 15 CSDD items were modified across 3 interview rounds; specifically, definitions for the vomiting and diarrhea frequency items were clarified for consistent interpretation and response. Interview participants also reported general ease in understanding and responding to the Pre–COVID-19 questionnaire, with feedback resulting in only minor changes to the reference period and instructions.Conclusion: The findings of the current study provide strong evidence for the content validity of the CSDD and the appropriateness of each of the items assessed. This rigorous evaluation (aligned with regulatory guidance) indicates that the CSDD is fit for the purpose of supporting efficacy endpoints in planned clinical trials evaluating medications for COVID-19 treatment.Keywords: patient-reported outcome measures, COVID-19, qualitative, symptom burden

Introduction: Niacin is underutilised because of flushing. Lack of a quantitative tool to assess niacin-induced flushing has precluded the objective evaluation of flushing associated with extended-release (ER) niacin formulations. We developed the Flushing Symptom Questionnaire© (FSQ), a quantitative tool to assess patient-reported flushing, and assessed its ability to characterise ER niacin-induced flushing. Methods: This study focused on the responses to one question in the FSQ, the Global Flushing Severity Score (GFSS), reported on a 0–10 scale (none = 0, mild = 1–3, moderate = 4–6, severe = 7–9 and extreme = 10) to assess flushing during ER niacin initiation (week 1) and maintenance (weeks 2–8). Results: Flushing severity with ER niacin was greatest during week 1 and remained greater than placebo for the study duration. During weeks 2–8, 40% of patients on ER niacin vs. 8% of those on placebo had > 1 day/week with ‘moderate or greater’ GFSS. Conclusions: In conclusion, the GFSS component of the FSQ was a sensitive and responsive quantitative measure of ER niacin-induced flushing that will aid in the objective comparison of novel strategies intended to improve tolerability and adherence to niacin, an agent proven to reduce cardiovascular risk. [ABSTRACT FROM AUTHOR]

Abstract Background The literature on changes in health-related quality of life (HRQOL) in weight loss studies is inconsistent, and few studies use more than one type of measure. The purpose of the current study was to compare one-year changes in HRQOL as a function of weight change using three different measures: a weight-related measure (Impact of Weight on Quality of Life-Lite [IWQOL-Lite)]) and two generic measures (SF-36; EQ-5D). Methods Data were obtained from 926 participants (mean Body Mass Index (BMI) (kg/m2) = 35.4; 84% female; mean age = 49.5 years) in a placebo-controlled randomized trial for weight loss. At baseline and one-year, participants completed all three HRQOL measures. HRQOL was compared across weight change categories (≥ 5% and 0–4.9% gain, 0–4.9%, 5.0–9.9% and ≥ 10% loss), using effect sizes. Results The weight-related measure of HRQOL exhibited greater improvements with one-year weight loss than either of the generic instruments, with effect sizes ranging from 0.24 to 0.62 for 5–9.9% weight reductions and 0.44 to 0.95 for ≥ 10% reductions. IWQOL-Lite Self-Esteem also showed a small improvement with weight gain. Changes in the two generic measures of HRQOL were inconsistent with each other, and in the case of the SF-36, variable across domains. For participants gaining ≥ 5% of weight, the greatest reductions in HRQOL occurred with respect to SF-36 Mental Health, MCS, and Vitality, with effect sizes of -0.82, -0.70, and -0.63 respectively. Conclusion This study found differences between weight-related and generic measures of health-related quality of life in a one-year weight loss trial, reflecting the potential value of using more than one measure in a trial. Although weight loss was generally associated with improved IWQOL-Lite, physical SF-36 subscale and EQ-5D scores, a small amount of weight gain was associated with a slight improvement on weight-specific HRQOL and almost no change on the EQ-5D, suggesting the need for further research to more fully study these relationships. We believe our findings have relevance for weight loss patients and obesity clinicians/researchers in informing them of likely HRQOL outcomes associated with varying amounts of weight loss or gain.

Background: Respiratory syncytial virus (RSV) causes significant morbidity and mortality in older adults. Despite a number of RSV vaccine candidates in clinical trials, there are no existing disease-specific, self-reported measures that assess the symptoms and severity of RSV infection from the perspective of adult patients with acute RSV. The objective of this study was to describe the initial conceptualization and development of the RSV Infection, Intensity and Impact Questionnaire (RSV-iiiQ), a new patient-reported outcome measure., Methods: A targeted review of the literature identified relevant existing measures, symptoms, and impacts of RSV. A draft version of the RSV-iiiQ was developed based on the Influenza Intensity and Impact Questionnaire (Flu-iiQ) with expert input. Qualitative interviews (N = 20) were conducted with participants to optimize the RSV-iiiQ conceptual model and confirm the content validity of the RSV-iiiQ. Interviews included concept elicitation and a cognitive debriefing assessment. A draft conceptual framework was developed, and the electronic clinical outcome assessment was piloted. All steps of instrument development followed Food and Drug Administration guidance for patient-reported outcomes., Results: In-depth concept elicitation interviews followed by cognitive debriefings demonstrated that the content of the items was comprehensive, covered the breadth of RSV symptoms and impacts, and was relevant to the experiences of individuals with RSV. Both the paper and electronic versions of the RSV-iiiQ were easily completed. Minor refinements were made to some items based on participant feedback, and the draft conceptual framework was refined., Conclusions: The RSV-iiiQ was developed for use in clinical trials to measure the symptom intensity and impact of acute RSV infection from the perspective of adult patients. The tool was developed in accordance with current regulatory guidance and is useful to support patient-focused drug development., (© 2023. Merck & Co., Inc., Rahway, NJ, USA and its affiliates.)

Objectives: To assess health-related quality of life (HRQoL) with first-line pembrolizumab, pembrolizumab-chemotherapy, or cetuximab-chemotherapy in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) in the phase 3 KEYNOTE-048 trial (NCT02358031)., Materials and Methods: HRQoL was measured using the European Organisation for Research and Treatment of Cancer 30-question quality-of-life (EORTC QLQ-C30), the EORTC 35-question quality-of-life head and neck cancer-specific module (EORTC QLQ-H&N35), and the EuroQol 5-dimension 3-level instruments (EQ-5D-3L). Secondary endpoints included mean change from baseline in EORTC QLQ-C30 global health status/quality of life (GHS/QoL) at week 15 and time to deterioration (TTD) in EORTC QLQ-C30 GHS/QoL and EORTC QLQ-H&N35 pain and swallowing., Results: Of 882 enrolled participants, 844 received ≥ 1 dose of study treatment and completed ≥ 1 HRQoL assessment; adherence was ≥ 79% at week 15 across treatment groups. At week 15, EORTC QLQ-C30 GHS/QoL scores remained stable; no clinically meaningful between-group differences were observed (least squares mean difference, pembrolizumab vs cetuximab-chemotherapy, 0.24; 95% CI, -3.34 to 3.82; pembrolizumab-chemotherapy vs cetuximab-chemotherapy, 0.40; 95% CI, -3.46 to 4.26). Median TTD in EORTC QLQ-C30 GHS/QoL and EORTC QLQ-H&N35 pain and swallowing scores was not reached over 51 weeks across groups, showing stable HRQoL. TTD was similar between groups for EORTC QLQ-C30 GHS/QoL (pembrolizumab vs cetuximab-chemotherapy: HR, 1.38; 95% CI, 0.95-2.00; pembrolizumab-chemotherapy vs cetuximab-chemotherapy: HR, 1.37; 95% CI, 0.94-2.00), as was TTD in EORTC QLQ-H&N35 pain and swallowing scores., Conclusions: Pembrolizumab monotherapy and pembrolizumab-chemotherapy extended OS while maintaining HRQoL, further supporting first-line use for R/M HNSCC., (Copyright © 2022 Merck Sharp & Dohme Corp, The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: In the phase III KEYNOTE-181 study (NCT02564263) of patients with advanced esophageal cancer (EC), pembrolizumab monotherapy prolonged overall survival versus chemotherapy as second-line therapy in patients with programmed death ligand 1 combined positive score (CPS) ≥ 10. We present the results of the prespecified health-related quality-of-life (HRQoL) analyses of the squamous cell carcinoma (SCC), CPS ≥ 10, and CPS ≥ 10 SCC populations., Patients and Methods: HRQoL was measured using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30), EORTC QLQ EC questionnaire (OES18), and EuroQol 5-dimension questionnaire (EQ-5D). Data were analyzed in patients who received ≥ 1 dose of study treatment and completed ≥ 1 HRQoL assessment. Key analyses included baseline to week 9 least squares mean change in global health status/quality of life, functional or symptom subscales, and time to deterioration (≥ 10-point deterioration) for specific subscales., Results: The HRQoL population included 387 patients with SCC. Compliance and completion rates for all three questionnaires were similar in both treatment groups at baseline and week 9. No clinically meaningful differences in global health status/quality of life scores were observed between treatment groups from baseline to week 9 (least squares mean difference, 2.80; 95% CI, -1.48 to 7.08); patients in both treatment groups generally exhibited stable functioning and symptom scores of the QLQ-C30 and QLQ-OES18 from baseline to week 9. Time to deterioration for pain (hazard ratio [HR], 1.22; 95% CI, 0.79 to 1.89), reflux (HR, 2.38; 95% CI, 1.33 to 4.25), and dysphagia (HR, 1.53; 95% CI, 1.02 to 2.31) subscales were similar between treatment groups. These findings were generally similar in the CPS ≥ 10 (n = 218) and CPS ≥ 10 SCC (n = 166) subgroups., Conclusion: In patients with advanced EC, pembrolizumab monotherapy and chemotherapy maintained HRQoL in patients with SCC, CPS ≥ 10, and CPS ≥ 10 SCC., Competing Interests: Antoine AdenisHonoraria: Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc, Kenilworth, NJ, Bristol Myers SquibbConsulting or Advisory Role: Bristol Myers Squibb, Merck, Merck SeronoResearch Funding: Bayer (Inst)Travel, Accommodations, Expenses: Bristol Myers Squibb, Merck Amit S. KulkarniEmployment: MerckStock and Other Ownership Interests: Merck Gustavo C. GirottoConsulting or Advisory Role: MSDSpeakers' Bureau: MSDResearch Funding: MSD (Inst) Christelle de la FouchardiereHonoraria: Merck Serono, RocheConsulting or Advisory Role: Lilly, Bayer, Amgen, Bristol Myers Squibb, Servier, Roche¸ Pierre Fabre OncologyResearch Funding: Roche (Inst)Travel, Accommodations, Expenses: Roche, Celgene, Amgen, Bristol Myers Squibb, Servier, RocheOther Relationship: Incyte, MSD Hanneke W. M. van LaarhovenConsulting or Advisory Role: Nordic Pharma, Lilly, Bristol Myers Squibb, Servier, MSDResearch Funding: Bristol Myers Squibb (Inst), Bayer (Inst), Lilly (Inst), Nordic Pharma (Inst), MSD, Servier (Inst) Wasat MansoorHonoraria: BMS, ServierConsulting or Advisory Role: BMS, Servier Raed Al-RajabiHonoraria: AstraZeneca, BayerSpeakers' Bureau: Sirtex Josephine NorquistEmployment: MerckStock and Other Ownership Interests: Merck Mayur AmonkarEmployment: Merck Shailaja SuryawanshiEmployment: Merck Pooja BhagiaEmployment: Merck Jean-Philippe MetgesHonoraria: BMS, Bayer, MSDNo other potential conflicts of interest were reported.

Background: In the randomised phase III KEYNOTE-062 study, pembrolizumab was non-inferior to chemotherapy for overall survival in patients with programmed death-ligand 1 (PD-L1)-positive [combined positive score (CPS) ≥1] advanced gastric/gastroesophageal junction (GEJ) cancer. We present findings of prespecified health-related quality-of-life (HRQOL) analyses for pembrolizumab versus chemotherapy in this population., Materials and Methods: HRQOL, a secondary endpoint, was measured in patients who received ≥1 dose of study treatment and completed ≥1 HRQOL questionnaire [European Organisation for the Research and Treatment of Cancer (EORTC) 30-question quality-of-life (QLQ-C30), EORTC 22-question quality-of-life gastric-cancer-specific module (QLQ-STO22)]. Least squares mean (LSM) change (baseline to week 18) in global health status/quality of life (GHS/QOL; EORTC QLQ-C30) and time to deterioration (TTD) in GHS/QOL, nausea/vomiting and appetite loss scores (EORTC QLQ-C30) and abdominal pain/discomfort scores (EORTC QLQ-STO22) were evaluated., Results: The HRQOL population comprised 495 patients with CPS ≥1 (pembrolizumab, 252; chemotherapy, 243). Compliance rates at week 18 were similar for pembrolizumab and chemotherapy (EORTC QLQ-C30, 87.9% and 81.9%; EORTC QLQ-STO22, 87.9% and 81.3%, respectively). There was no between-arm difference in LSM score change in GHS/QOL [-0.16; 95% confidence interval (CI) -5.01 to 4.69; P = 0.948]. The LSM score change for most subscales showed comparable worsening in both arms. TTD for GHS/QOL [hazard ratio (HR), 0.96; 95% CI, 0.67-1.38; P = 0.826], appetite loss (HR, 0.83; 95% CI, 0.58-1.20; P = 0.314) and pain (HR, 1.22; 95% CI, 0.78-1.91; P = 0.381) were similar between arms. Longer TTD was observed for pembrolizumab versus chemotherapy for nausea/vomiting (HR, 0.61; 95% CI, 0.44-0.85; P = 0.003)., Conclusions: HRQOL was maintained with first-line treatment with pembrolizumab in patients with PD-L1-positive advanced gastric/GEJ cancer and was similar between pembrolizumab and chemotherapy in this population., Competing Interests: Disclosure EVC reports advisory/consultancy fees from Array, AstraZeneca, Bayer, BioPharma, Bristol Myers Squibb, Celgene, Halozyme, Lilly, Merck KGaA, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Novartis, Roche and Servier; and researching grant/funding (institution) from Amgen, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Ipsen, Lilly, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA., Merck KGaA, Novartis, Roche and Servier. AV is an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Y-JB reports consulting/advisory role for Astellas, AstraZeneca, Bayer, BeiGene, Bristol Myers Squibb, Daichii-Sankyo, Eli Lilly, Genentech/Roche, Genexine, Green Cross, Hanmi, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Merck Serono, Novartis, Samyang Biopharmaceuticals and Taiho; and grants (to the institution for clinical trials) from Astellas, AstraZeneca, Bayer, BeiGene, Bristol Myers Squibb, Boehringer Ingelheim, Boston Biomedical, CKD Pharma, Curis, Daiichi Sankyo, Eli Lilly, Five Prime, Genentech/Roche, Genexine, Green Cross, GSK, MacroGenics, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Merck Serono, Novartis, Ono, Pfizer, Taiho and Takeda. CSF reports consulting role for Agios, Amylin Pharmaceuticals, Bain Capital, CytomX Therapeutics, Daiichi Sankyo, Eli Lilly, Entrinsic Health, EvolveImmune Therapeutics, Genentech, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Taiho and Unum Therapeutics. He also serves as a director for CytomX Therapeutics and owns unexercised stock options for CytomX and Entrinsic Health. He is a co-founder of EvolveImmune Therapeutics and has equity in this private company. KS reports grants and personal fees from Astellas Pharma, Eli Lilly and Company, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Ono Pharmaceutical and Taiho Pharmaceutical; personal fees from AbbVie, Bristol Myers Squibb, GlaxoSmithKline, Novartis, Pfizer Inc., Takeda Pharmaceuticals and Yakult; and grants from Chugai Pharma, Daiichi Sankyo, Dainippon Sumitomo Pharma and Medi Science. YYJ reports advisory fees from Bristol Myers Squibb, Lilly, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Merck Serono and Pfizer; and research expenses from Amgen, Bayer, Boehringer Ingelheim, Genentech, Lilly and Roche. VS reports research funding from Bristol Myers Squibb, EMD-Serono and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. SSt reports advisory/consultancy role for Bayer, Bristol Myers Squibb, Exelixis, Genentech, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and QED. JMN is an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. UK is an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. SSh is an employee and a stockholder of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. MA reports scientific consultancy role for Bristol Myers Squibb, Lilly, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Servier; and honoraria for speaking for Bristol Myers Squibb, Lilly, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Servier. All other authors have declared no conflicts of interest., (Copyright © 2021. Published by Elsevier Ltd.)

Patient-reported outcomes (PROs) are used in clinical trials to provide valuable evidence on the impact of disease and treatment on patients' symptoms, function and quality of life. High-quality PRO data from trials can inform shared decision-making, regulatory and economic analyses and health policy. Recent evidence suggests the PRO content of past trial protocols was often incomplete or unclear, leading to research waste. To address this issue, international, consensus-based, PRO-specific guidelines were developed: the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT)-PRO Extension. The SPIRIT-PRO Extension is a 16-item checklist which aims to improve the content and quality of aspects of clinical trial protocols relating to PRO data collection to minimise research waste, and ultimately better inform patient-centred care. This SPIRIT-PRO explanation and elaboration (E&E) paper provides information to promote understanding and facilitate uptake of the recommended checklist items, including a comprehensive protocol template. For each SPIRIT-PRO item, we provide a detailed description, one or more examples from existing trial protocols and supporting empirical evidence of the item's importance. We recommend this paper and protocol template be used alongside the SPIRIT 2013 and SPIRIT-PRO Extension paper to optimise the transparent development and review of trial protocols with PROs., Competing Interests: Competing interests: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and declare: SPIRIT-PRO group members were reimbursed for travel/subsistence at the consensus meeting. MC is Director of the Birmingham Health Partners Centre for Regulatory Science and Innovation, Director of the Centre for the Centre for Patient Reported Outcomes Research and is a National Institute for Health Research (NIHR) Senior Investigator. MC has received personal fees from Astellas, Takeda, Merck, Daiichi Sankyo, Glaukos, GSK and the Patient-Centred Outcomes Research Institute (PCORI) outside the submitted work. RM-B reports non-financial support from University of Birmingham. OA, DK and ARet report grants from NIHR. OA and DK report grants from Birmingham Biomedical Research Centre (BRC). OA reports grants from UCB Pharma and also receives funding from the Health Foundation and declares personal fees from Gilead Sciences Ltd. DK and ARet report grants from Innovate UK and Macmillan Cancer Support. DK reports grants from Kidney Research UK, NIHR SRMRC at the University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, personal fees from Merck, GSK. EB declares personal fees from Navigating Cancer, Sivan Healthcare, CareVive Systems and AstraZeneca. Bell reports other from AstraZeneca, is an employee with stock ownership and/or stock options in the company. JCC reports other from Pfizer Inc., and is an employee and a stockholder of Pfizer Inc. IG is a fully paid employee of Boehringer Ingelheim International GmbH. CE is Chair of the Government of Canada Interagency Advisory Panel on Research Ethics. LM reports non-financial support from Daiichi-Sankyo and Cell & Gene Therapy Catapult. Morel reports other from UCB. LN reports other from GlaxoSmithKline, including employment and ownership of stock in GSK. RS reports personal fees from BioMed Central and Pfizer, other from NHS England, NHSx, NDC, NCRI, NIHR, MRC CTU, GeL, Glasgow CTU, UCLH, LSHTM, Cancer Research UK, Macmillan, Warwick University, Warwick CTU and University of Birmingham. AW reports grants from NIHR and Innovate UK. All other authors have completed the ICMJE uniform disclosure form and declare no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous 3 years, no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: Patient-reported outcome (PRO) data from clinical trials can provide valuable evidence to inform shared decision making, labeling claims, clinical guidelines, and health policy; however, the PRO content of clinical trial protocols is often suboptimal. The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) statement was published in 2013 and aims to improve the completeness of trial protocols by providing evidence-based recommendations for the minimum set of items to be addressed, but it does not provide PRO-specific guidance., Objective: To develop international, consensus-based, PRO-specific protocol guidance (the SPIRIT-PRO Extension)., Design, Setting, and Participants: The SPIRIT-PRO Extension was developed following the Enhancing Quality and Transparency of Health Research (EQUATOR) Network's methodological framework for guideline development. This included (1) a systematic review of existing PRO-specific protocol guidance to generate a list of potential PRO-specific protocol items (published in 2014); (2) refinements to the list and removal of duplicate items by the International Society for Quality of Life Research (ISOQOL) Protocol Checklist Taskforce; (3) an international stakeholder survey of clinical trial research personnel, PRO methodologists, health economists, psychometricians, patient advocates, funders, industry representatives, journal editors, policy makers, ethicists, and researchers responsible for evidence synthesis (distributed by 38 international partner organizations in October 2016); (4) an international Delphi exercise (n = 137 invited; October 2016 to February 2017); and (5) consensus meeting (n = 30 invited; May 2017). Prior to voting, consensus meeting participants were informed of the results of the Delphi exercise and given data from structured reviews evaluating the PRO protocol content of 3 defined samples of trial protocols., Results: The systematic review identified 162 PRO-specific protocol recommendations from 54 sources. The ISOQOL Taskforce (n = 21) reduced this to 56 items, which were considered by 138 international stakeholder survey participants and 99 Delphi panelists. The final wording of the SPIRIT-PRO Extension was agreed on at a consensus meeting (n = 29 participants) and reviewed by external group of experts during a consultation period. Eleven extensions and 5 elaborations to the SPIRIT 2013 checklist were recommended for inclusion in clinical trial protocols in which PROs are a primary or key secondary outcome. Extension items focused on PRO-specific issues relating to the trial rationale, objectives, eligibility criteria, concepts used to evaluate the intervention, time points for assessment, PRO instrument selection and measurement properties, data collection plan, translation to other languages, proxy completion, strategies to minimize missing data, and whether PRO data will be monitored during the study to inform clinical care., Conclusions and Relevance: The SPIRIT-PRO guidelines provide recommendations for items that should be addressed and included in clinical trial protocols in which PROs are a primary or key secondary outcome. Improved design of clinical trials including PROs could help ensure high-quality data that may inform patient-centered care.

Background: The sublingual immunotherapy (SLIT) Report Card was developed to capture patient-reported local reactions from the administration of SLIT, based on the World Allergy Organization side-effect grading system. The objective was to evaluate understandability, usability, and translatability of the paper and electronic versions of the SLIT Report Card., Methods: Adults (aged 18+ years), adolescents (aged 12-17 years), and parents/caregivers and their children (aged 5-11 years) participated in two rounds of interviews, testing the paper version in Round 1, and both the paper and electronic versions in Round 2. Interviews assessed comprehension and usability by subjects. Translatability identified potential issues related to translation or cultural relevance., Results: Ten adults, ten adolescents, and ten parent/child dyads were interviewed. In general, subjects demonstrated a clear understanding of the instrument's content. However, some subjects were uncertain of or suggested clarifying the meaning of certain terms, including tablet, ulcer, taste alteration, uvula, nausea, and itching in the ear. The translatability assessment also identified uvula and nausea as potentially problematic for translation. Subjects could use the electronic device and found navigation 'easy', with only a few minor suggestions made to improve usability. Some wording and formatting changes were made based on subjects' feedback and the translatability assessment., Conclusion: The SLIT Report Card was refined following best practices for instrument development, including cognitive interviewing, usability, and translatability assessment. The refined SLIT Report Card is appropriate for comprehensively and systematically collecting SLIT-related local reactions directly from subjects in a clinical trial setting, taking into account the World Allergy Organization grading system.

Background: Patient-reported outcome (PRO) instruments are important tools for monitoring disease activity and response to treatment in clinical trials and clinical practice. In recent years, there have been movements away from traditional pen-and-paper PROs towards electronic administration. When using electronic PROs (ePROs), evidence that respondents complete ePROs in a similar way to their paper counterparts provides assurance that the two modes of administration are comparable or equivalent. The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 item (EORTC QLQ-C30) and associated disease-specific modules are among the most widely used PROs in oncology. Although studies have evaluated the comparability and equivalence of electronic and original paper versions of the EORTC QLQ-C30, no such studies have been conducted to date for the head and neck cancer specific module (EORTC QLQ-H&N35)., Objective: This study aimed to qualitatively assess the comparability of paper and electronic versions of the EORTC QLQ-H&N35., Methods: Ten head and neck cancer patients in the United States underwent structured cognitive debriefing and usability interviews. An open randomized crossover design was used in which participants completed the two modes of administration allocated in a randomized order. Using a "think-aloud" process, participants were asked to speak their thoughts aloud while completing the EORTC QLQ-H&N35. They were thoroughly debriefed on their responses to determine consistency in interpretation and cognitive process when completing the instrument in both paper and electronic format., Results: Participants reported that the EORTC QLQ-H&N35 demonstrated excellent qualitative comparability between modes of administration. The proportion of noncomparable responses (ie, where the thought process used by participants for selecting responses appeared to be different) observed in the study was low (11/350 response pairs [35 items x 10 participants]; 3.1%). Evidence of noncomparability was observed for 9 of the 35 items of the EORTC QLQ-H&N35 and in no more than 2 participants per item. In addition, there were no apparent differences in level of comparability between individual participants or between modes of administration., Conclusions: Mode of administration does not affect participants' response to, or interpretation of, items in the EORTC QLQ-H&N35. The findings from this study add to the existing evidence supporting the use of electronic versions of the EORTC instruments when migrated to electronic platforms according to best practice guidelines., (©Josephine Norquist, Diana Chirovsky, Teja Munshi, Chloe Tolley, Charlotte Panter, Adam Gater. Originally published in JMIR Cancer (http://cancer.jmir.org), 12.05.2017.)

Objective: Treatments and their mode of administration may represent a burden for patients and can therefore impact their health-related quality of life (HRQL) or treatment/health satisfaction. Patients with type 2 diabetes mellitus (T2DM) can be treated with oral hypoglycemic agents (OHAs), injectable medications (such as insulin), or a combination of agents. This review aimed to identify patient-reported outcome (PRO) instruments measuring HRQL and/or satisfaction that could differentiate between oral medications based on medication related attributes such as efficacy, tolerability, weight loss, dosing frequency and pill burden., Research Design and Methods: Medline, Embase, PsycINFO, Cochrane Library and the Patient-Reported Outcome and Quality of Life Questionnaires (PROQOLID) biomedical databases were searched to identify instruments and document their development methodology, content and psychometric properties (i.e. validity, reliability), responsiveness and ability to detect changes between treatments., Results: Nineteen instruments were retained based on their potential to differentiate between OHAs. Ten instruments assessed HRQL, amongst which the Audit of Diabetes Dependent Quality of Life, Diabetes 39, Diabetes Health Profile and Impact of Weight on Quality of Life displayed good psychometric properties in T2DM populations and comprehensive HRQL content. Nine instruments assessed satisfaction. Both the Oral Hypoglycemic Agent Questionnaire (OHAQ) and Diabetes Medication Satisfaction (DiabMedSat) Questionnaire have highly relevant content regarding drug attributes. The OHAQ is specific to oral treatment and the DiabMedSat includes HRQL items. The Diabetes Treatment Satisfaction Questionnaire is a standard instrument that is extensively used and provides conclusive results in studies of patients with T2DM., Conclusions: Very few of the existing PRO instruments are specific to OHAs. Despite satisfaction instruments being recommended to differentiate between OHAs in studies of T2DM based on medication attributes, we find that none of the existing instruments appear to be useful in detecting differences between treatments, therefore limiting their use in clinical and observational research.