Critical Comments by Food and Drug Administration Reviewers on Patient-Reported Outcomes in Food and Drug Administration Regulatory Submissions (2018-2021).

OBJECTIVES: This article examined the inclusion of patient-reported outcome (PRO) data in new drug applications (NDAs) submitted to the Food and Drug Administration (FDA) and approved from 2018 to 2021. The importance of assessing PROs, which capture patients' perspectives on the disease and treatment experience, has been underscored by many stakeholders, including regulatory authorities. Despite the increasing inclusion of PRO assessments in registration trials, inclusion of language related to PRO results in approved product labeling varies widely. METHODS: This study examined FDA submission packages for NDAs approved by the FDA from 2018 to 2021 to identify critical reviewer comments related to PROs. Comments were identified and categorized by the type of criticism. Reviewers considered both oncology and nononcology indications. RESULTS: Assessment of PROs was included in 66.2% of the 210 submissions reviewed. Critical comments were identified in 45.3% of these applications; comments most commonly related to statistical analysis considerations, fit for purpose, and study design. Other categories of critical comment included data quality, lack of treatment benefit, administrative considerations, and miscellaneous issues. Differences were observed between oncology and nononcology NDAs with regard to the number and type of comments included in each of these categories. The findings highlight the importance of planning statistical analyses, establishing content validity, carefully considering study design, maximizing data quality, and demonstrating treatment benefit, among other issues. CONCLUSIONS: Overall, this study offers insight into the landscape of PRO data included in recently approved NDAs, along with recommendations for improving the quality and reporting of PROs in clinical trials.

Recommendations to address respondent burden associated with patient-reported outcome assessment.

Patient-reported outcomes (PROs) are increasingly used in healthcare research to provide evidence of the benefits and risks of interventions from the patient perspective and to inform regulatory decisions and health policy. The use of PROs in clinical practice can facilitate symptom monitoring, tailor care to individual needs, aid clinical decision-making and inform value-based healthcare initiatives. Despite their benefits, there are concerns that the potential burden on respondents may reduce their willingness to complete PROs, with potential impact on the completeness and quality of the data for decision-making. We therefore conducted an initial literature review to generate a list of candidate recommendations aimed at reducing respondent burden. This was followed by a two-stage Delphi survey by an international multi-stakeholder group. A consensus meeting was held to finalize the recommendations. The final consensus statement includes 19 recommendations to address PRO respondent burden in healthcare research and clinical practice. If implemented, these recommendations may reduce PRO respondent burden.

Assessment of Patient-Reported Outcomes in Industry-Sponsored Phase I Oncology Studies: Considerations for Translating Theory Into Practice.

An increasing interest in the identification of optimal dosage for oncology therapies has prompted key opinion leaders and regulators to encourage the integration of patient-reported outcome (PRO) assessments in phase I oncology clinical trials. Although the potential benefits of assessing PROs in early-phase studies have been acknowledged, the difficulties that arise from such a radical shift have been largely overlooked in the public discussion. In this commentary, the authors provide insight into the challenges that industry sponsors face in integrating PRO assessments into phase I oncology trials, with the ultimate goal of facilitating conversations that may help to resolve some of these issues.

A Review of Patient-Reported Outcome Considerations in Oncologic Drugs Advisory Committee Meetings (2016-2021).

PURPOSE: The purpose of this project was to gain insight into the role of patient-reported outcome (PRO) data in US Food and Drug Administration (FDA) Oncologic Drugs Advisory Committee (ODAC) reviews and recommendations by documenting PRO-related considerations that appear in transcripts of ODAC meetings over a 6-year period (2016-2021). METHODS: ODAC meeting transcripts were reviewed for any mention of PRO-related concepts. Meetings that reviewed biosimilars and meetings that discussed conceptual matters were excluded. For each identified transcript, the meeting date, brand and generic names of the drug, and indication were collected from the meeting minutes. Comments by ODAC members, FDA reviewers, and study sponsors on PRO data were captured during the review. Qualitative review of transcripts included both reading and searching for key terms, including PROs, quality of life, and health-related quality of life. Discussion of PRO-related topics was captured verbatim, organized thematically, and analyzed by two independent reviewers. RESULTS: Twenty-seven transcripts of reviews were identified for 2016-2021. Topics related to PROs were included in 12 of those 27 reviews. The ODAC was satisfied with PROs included in 2 of those 12 reviews. Reasons for dissatisfaction in 10 of the 12 reviews included key concepts not assessed (5/12), missing data (5/12), and disagreement with sponsors' interpretation (3/12). The ODAC also expressed dissatisfaction with the lack of PRO data in 6 of 15 reviews that did not include PROs. CONCLUSION: Less than half of ODAC reviews in 2016-2021 included PROs, and reviewers expressed frustration at the lack of PRO data. Even when included, evidence on the basis of PROs was rarely deemed adequate for benefit-risk assessments.

A Review of Labeling Based on Patient-Reported Outcome Endpoints for New Oncology Drugs Approved by the European Medicines Agency (2017-2021).

OBJECTIVE: A review of new oncology indications approved by the European Medicines Agency (EMA) for 2012-2016 showed that 33% of new drugs had labeling based on patient-reported outcomes (PROs). We reviewed labeling text based on PRO endpoints for new oncology indications approved during 2017-2021. METHODS: New oncology drugs approved by EMA to treat indications of cancers during 2017-2021 were identified from the EMA website. PRO-related language reported in EMA summaries of product characteristics (SmPCs) were summarized and compared with similar findings reported for oncology indications approved during 2012-2016. RESULTS: Review documents by the EMA during 2017-2021 were available for 49 new oncology drugs for 70 cancer indications. Submissions for 52 (74.3%) of the 70 indications included PRO data for EMA review. Of all submissions, 14 (20.0%) approvals contained PRO-related language in the SmPC. Broad concepts such as health-related quality of life were most common and found in 8 of 14 (57.1%) PRO-related labels. CONCLUSION: PRO-related language appeared in SmPCs for 20% of all indications of new oncology drugs approved by EMA during 2017-2021 compared with approximately 33% of EMA approvals during 2012-2016. PRO-related labeling during the same periods showed a greater decline (from 47% to 27%) for indications of new oncology drugs that also included PRO data. One possible reason for this decline may be the increase in open-label studies from 62% between 2012 and 2016 to approximately 79% between 2017 and 2021.

Quality of life improvements following one year of setmelanotide in children and adult patients with Bardet-Biedl syndrome: phase 3 trial results.

BACKGROUND: Bardet-Biedl syndrome is a rare genetic disease associated with hyperphagia and early-onset, severe obesity. There is limited evidence on how hyperphagia and obesity affect health-related quality of life in patients with Bardet-Biedl syndrome, and on how management of these symptoms may influence disease burden. This analysis evaluated changes in health-related quality of life in adults and children with Bardet-Biedl syndrome in a Phase 3 trial following 1 year of setmelanotide treatment (ClinicalTrials.gov identifier: NCT03746522). METHODS: Patients with Bardet-Biedl syndrome and obesity received 52 weeks of treatment with setmelanotide and completed various self-reported health-related quality of life measures. Patients aged < 18 years or their caregiver completed the Pediatric Quality of Life Inventory (PedsQL; meaningful improvement, 4.4-point change); adults aged ≥ 18 years completed the Impact of Weight on Quality of Life Questionnaire-Lite (IWQOL-Lite; meaningful improvement range, 7.7-12-point change). Descriptive outcomes were reported in patients with data both at active treatment baseline and after 52 weeks of treatment. RESULTS: Twenty patients (< 18 years, n = 9; ≥ 18 years, n = 11) reported health-related quality of life at baseline and 52 weeks. For children and adolescents, PedsQL score mean change from baseline after 52 weeks was + 11.2; all patients with PedsQL impairment at baseline (n = 4) experienced clinically meaningful improvement. In adults, IWQOL-Lite score mean change from baseline was + 12.0. Of adults with IWQOL-Lite impairment at baseline (n = 8), 62.5% experienced clinically meaningful improvement. In adults, IWQOL-Lite score was significantly correlated with changes in percent body weight (P = 0.0037) and body mass index (P = 0.0098). CONCLUSIONS: After 1 year of setmelanotide, patients reported clinically meaningful improvements across multiple health-related quality of life measures. This study highlights the need to address the impaired health-related quality of life in Bardet-Biedl syndrome, and supports utility of setmelanotide for reducing this burden. Trial Registration NCT03746522. Registered November 19, 2018, https://clinicaltrials.gov/ct2/show/NCT03746522 .

A review of patient-reported outcome assessments in registration trials of FDA-approved new oncology drugs (2014-2018).

The Food and Drug Administration (FDA) encourages the assessment of patient-reported outcomes (PROs) in oncology clinical trials. A 2015 review showed that approximately 26% of industry-sponsored oncology trials included assessment of PROs. However, the proportion of recent trials that supported new oncology drug approvals and assessed PROs is unknown. This review found that assessment of PROs was included in about 75% of registration trials that supported 55 new FDA drug approvals during 2014-2018. Patient-reported outcome assessment was included more in randomized controlled trials than in open-label trials (88% vs. 69%, respectively) and more in phase 3 than in phase 2 trials (89% vs. 66%, respectively).

Patient experiences with patient-reported outcome measures in metastatic breast cancer trials: qualitative interviews.

BACKGROUND: Patient-reported outcome (PRO) measures are critical for assessing treatment benefit of anticancer treatments. Although PRO measures have been developed with the intention of capturing patient-centric concepts, a gap exists in understanding the patient experience with these tools. We characterized the experience of patients with metastatic breast cancer (mBC) with PRO measures in an oncology clinical trial setting to determine the importance, relevance, barriers, and facilitators for PRO completion. METHODS: The multicenter, qualitative design included semistructured interviews with 18 women with mBC who completed PRO measures in a clinical trial setting within 1 year of screening. Interviews began with concept elicitation to understand symptom characterization, decision to participate in a clinical trial, pre-trial expectations, and thoughts on study-related questionnaires. Cognitive debriefing was conducted to determine if items in a commonly used PRO instrument were relevant to the patient experience. Qualitative data were analyzed using a constant comparative approach. RESULTS: Participants described the need for detailed explanation of PRO measures at study start, including information about how the PRO data will likely be used to support drug development. Respondents who felt connected to clinical trial research were more likely to feel as if the measures adequately captured their experiences. Items that were deemed irrelevant or out of date to the patient experience may cause a respondent to feel marginalized and adds to the overall burden of PRO measure completion. Mode of PRO measure administration (electronic/paper) was important to some, but placement of the instrument completion within a study visit appeared to influence respondent willingness to fully engage with the measures. A lack of any type of feedback loop to allow respondents to learn from the captured PRO data was noted as important but missing from the patient experience. CONCLUSIONS: PRO measures need to include content that is relevant to the patient experience over the course of the clinical trial period to be considered meaningful to respondents, and administration techniques also impact engagement. Robust communication strategies that socialize the intent, use, and results of PRO data may enrich the patient experience and support greater adherence to PRO completion in future studies.

Ethical Considerations for the Inclusion of Patient-Reported Outcomes in Clinical Research: The PRO Ethics Guidelines.

Importance: Patient-reported outcomes (PROs) can inform health care decisions, regulatory decisions, and health care policy. They also can be used for audit/benchmarking and monitoring symptoms to provide timely care tailored to individual needs. However, several ethical issues have been raised in relation to PRO use. Objective: To develop international, consensus-based, PRO-specific ethical guidelines for clinical research. Evidence Review: The PRO ethics guidelines were developed following the Enhancing the Quality and Transparency of Health Research (EQUATOR) Network's guideline development framework. This included a systematic review of the ethical implications of PROs in clinical research. The databases MEDLINE (Ovid), Embase, AMED, and CINAHL were searched from inception until March 2020. The keywords patient reported outcome* and ethic* were used to search the databases. Two reviewers independently conducted title and abstract screening before full-text screening to determine eligibility. The review was supplemented by the SPIRIT-PRO Extension recommendations for trial protocol. Subsequently, a 2-round international Delphi process (n = 96 participants; May and August 2021) and a consensus meeting (n = 25 international participants; October 2021) were held. Prior to voting, consensus meeting participants were provided with a summary of the Delphi process results and information on whether the items aligned with existing ethical guidance. Findings: Twenty-three items were considered in the first round of the Delphi process: 6 relevant candidate items from the systematic review and 17 additional items drawn from the SPIRIT-PRO Extension. Ninety-six international participants voted on the relevant importance of each item for inclusion in ethical guidelines and 12 additional items were recommended for inclusion in round 2 of the Delphi (35 items in total). Fourteen items were recommended for inclusion at the consensus meeting (n = 25 participants). The final wording of the PRO ethical guidelines was agreed on by consensus meeting participants with input from 6 additional individuals. Included items focused on PRO-specific ethical issues relating to research rationale, objectives, eligibility requirements, PRO concepts and domains, PRO assessment schedules, sample size, PRO data monitoring, barriers to PRO completion, participant acceptability and burden, administration of PRO questionnaires for participants who are unable to self-report PRO data, input on PRO strategy by patient partners or members of the public, avoiding missing data, and dissemination plans. Conclusions and Relevance: The PRO ethics guidelines provide recommendations for ethical issues that should be addressed in PRO clinical research. Addressing ethical issues of PRO clinical research has the potential to ensure high-quality PRO data while minimizing participant risk, burden, and harm and protecting participant and researcher welfare.

A Review of Patient-Reported Outcome Labeling of FDA-Approved New Drugs (2016-2020): Counts, Categories, and Comprehensibility.

OBJECTIVES: A review of new drug approvals (NDAs) by the US Food and Drug Administration (FDA) for 2006 to 2015 showed that approximately 20% of new drugs had labeling based on patient-reported outcomes (PROs). The purpose of this study was to review labeling text based on PRO endpoints for NDAs from 2016 to 2020, with a special focus on the comprehensibility of such statements when included. METHODS: We reviewed drug approval reports on the Drugs@FDA web page of the FDA website to determine the number of NDAs from 2016 to 2020. For all identified NDAs, drug approval package and product labels were reviewed. NDAs from 2016 to 2020 were grouped by disease category as per International Classification of Diseases 10th Revision. Data were summarized for diseases that traditionally rely on PROs for evaluating treatment benefit (PRO dependent) and for diseases that traditionally do not rely on PROs (non-PRO dependent). Results were compared with NDAs from 2006 to 2010. RESULTS: NDAs amounting to 228 were identified from 2016 to 2020, 26.3% of which had labeling statements based on PRO endpoints. From 2006 to 2015 and from 2016 to 2020, PRO labeling statements were included in 46.5% (46 of 99) and 50.0% (47 of 94), respectively, of NDAs for PRO-dependent new molecular entities and in 6.0% (12 of 199) and 9.7% (13 of 199), respectively, of NDAs for non-PRO-dependent new molecular entities. Comprehensibility of labeling statements based on PRO endpoints was judged to be complex in 56.7% of product labels. CONCLUSIONS: The increase in labeling text based on PRO endpoints in product labels is encouraging. However, there is room for improvement on the comprehensibility of labeling statements based on PRO endpoints.

Quality of life outcomes in two phase 3 trials of setmelanotide in patients with obesity due to LEPR or POMC deficiency.

INTRODUCTION: Individuals with proopiomelanocortin (POMC) or leptin receptor (LEPR) deficiency are young and experience severe obesity, hyperphagia, and comorbidities, which can impair quality of life (QOL). METHODS: Two pivotal Phase 3 trials explored the effect of setmelanotide on body weight and hunger in individuals with obesity due to POMC (NCT02896192) or LEPR (NCT03287960) deficiency. QOL and depression were investigated in parallel using the disease-specific, age-appropriate Impact of Weight on Quality of Life-Lite (IWQOL-Lite), Pediatric Quality of Life Inventory (PedsQL), and Patient Health Questionnaire-9 (PHQ-9). RESULTS: In total, the POMC and LEPR trials enrolled 21 patients. Adults (≥ 18 years old; n = 7) had moderate-to-severe impairment in QOL at baseline, with mean (standard deviation [SD]) IWQOL-Lite total score 60.3 (13.2; maximum IWQOL-Lite total score = 100). The effect of setmelanotide on IWQOL-Lite total score was observed as soon as Week 5. Among those with scores at Week 52, 5 of 6 adults experienced a clinically meaningful improvement, with mean (SD) total scores increased from baseline by 24.2 (12.1) points. Children (6-12 years old; n = 2) and adolescents (13-17 years old; n = 4) had impaired QOL at baseline, with mean (SD) self-reported PedsQL total scores 53.3 (6.2) and 63.3 (29.1), respectively (maximum PedsQL total score = 100). Three of 5 patients experienced clinically meaningful improvement in PedsQL, with 2 children whose PedsQL total score increased by 28.3 and 3.3 points and 3 adolescents whose mean (SD) total score increased from baseline by 5.8 (18.3) points. Baseline mean (SD) PHQ-9 score (in those ≥ 12 years old) was 5.3 (3.8) and was generally maintained through Week 52. CONCLUSIONS: Patients with POMC or LEPR deficiency had impaired, and in some cases severely impaired, QOL before setmelanotide treatment. Setmelanotide improved QOL in patients as early as Week 5, with some patients no longer experiencing impaired QOL at Week 52. Improvements in QOL may be related to a reduction in hunger and body weight associated with setmelanotide. Because of the highly complex psychological consequences of rare genetic diseases of obesity, some patients may require a long period of treatment to improve QOL and benefit from interdisciplinary care.

Health-Related Quality of Life, Symptoms, and Tolerability of Loncastuximab Tesirine in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma.

BACKGROUND: Loncastuximab tesirine has shown antitumor activity with an acceptable toxicity profile in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who were relapsed or refractory after ≥2 prior therapies, including activity in patients with high-risk disease characteristics. This analysis examined health-related quality of life (HRQoL), symptoms, and tolerability in patients receiving loncastuximab tesirine for relapsed or refractory DLBCL. PATIENTS AND METHODS: The single-arm, open-label phase II LOTIS-2 study (ADCT-402-201; NCT03589469) enrolled 145 patients aged ≥18 years. Patients received loncastuximab tesirine as a 30-minute intravenous infusion on day 1 of each 3-week treatment cycle. Patient-reported outcomes were measured using EQ-5D and FACT-Lym at baseline, day 1 of each cycle, and the end-of-treatment visit. RESULTS: During the course of treatment, EQ VAS overall health score was improved over time. The adjusted improvement was 0.65 per cycle (95% CI, 0.26-1.04; P = .001), and the adjusted mean change from baseline score was 5.00 (95% CI, 1.75-8.25; P = .003) at cycle 9, day 1. FACT-Lym total scores remained stable during treatment. More patients reported improvement compared to baseline in pain, lumps/swelling, and losing weight for a majority of visits. More than 60% of patients reported being "not at all" or "a little bit" bothered by treatment side effects for all treatment visits. Findings in elderly patients were similar to the population as whole. CONCLUSION: The findings on HRQoL, symptoms, and tolerability further support the clinical use of loncastuximab tesirine for the treatment of relapsed or refractory DLBCL. FUNDING: This work was funded by ADC Therapeutics SA. Authors affiliated with ADC Therapeutics SA participated in designing the study; in collecting, analyzing, and interpreting the data; in writing the report; and in the decision to submit the article for publication.

Use of Patient and Investigator Global Impression Scales: A Review of Food and Drug Administration-Approved Labeling, 2009 to 2019.

OBJECTIVE: Identify disease categories in which single-item global impression (GI) scales were included in product labeling of new drugs approved by the US Food and Drug Administration (FDA) in January 2009-December 2019 and review the characteristics of GIs included in product labeling of new FDA-approved drugs (January 2017-December 2019). METHODS: FDA Clinical Outcome Assessment (COA) Compendium was reviewed for drug labels that included GIs for drugs approved in 2009-2016. The indication, year of approval, ICD-10 code, and GI respondent were noted. A manual review of labels of FDA-approved drugs (2017-2019) was undertaken to identify GIs included in the labels. Corresponding drug approval packages were reviewed to identify details of any regulatory reviewer comments related to GIs. GI characteristics were noted from the drug label or the review documents, including the respondent, type of measure (static or dynamic), item wording, concept assessed, and response options. RESULTS: Product labeling containing GIs was most common in diseases related to the skin, nervous system, behavioral disorders, and the musculoskeletal system. GIs were included in 30/77 (39.0%) drug labels in the four disease categories. CONCLUSION: In the past 10 years, GIs have been included as endpoint measures in confirmatory clinical trials and have generated evidence of treatment benefit in diseases related to the skin, nervous system, behavioral disorders, and the musculoskeletal system. GIs frequently provide important insights into the patient experience. Before GIs are included in clinical trials to assess treatment benefit, it is important to ensure that they are valid, reliable, and responsive.

Quality of life is maintained with ixazomib maintenance in post-transplant newly diagnosed multiple myeloma: The TOURMALINE-MM3 trial.

OBJECTIVES: Health-related quality of life (HRQoL) is particularly important during maintenance therapy (MT) in newly diagnosed multiple myeloma post-transplant, when disease symptoms are limited. METHODS: We assessed HRQoL in patients randomised to 26 cycles of MT (ixazomib vs placebo) in TOURMALINE-MM3 (NCT02181413). RESULTS: The characteristics at study entry were well-balanced between ixazomib (n = 386) and placebo (n = 251) arms. At study entry, EORTC QLQ-C30 and MY20 scores were high for functional scales and low for symptom scales and were comparable with those of the general population. Changes in subscale scores across intervals, analysed over 30 four-week intervals using a linear mixed-effects model, were generally small and similar between arms for the EORTC QLQ-C30 Global Health Status/QoL, Physical Functioning, and Pain subscales and EORTC QLQ-MY20 Disease Symptoms subscale and Peripheral Neuropathy item. EORTC QLQ-C30 Nausea/Vomiting and Diarrhoea subscales were consistently worse for ixazomib than for placebo, in line with the ixazomib toxicity profile. Even when least-squares mean differences between arms were statistically significant, none reached the established minimal important clinical difference of 10 in multiple myeloma. CONCLUSIONS: In addition to improvement in progression-free survival with ixazomib, HRQoL was maintained in both arms. Active treatment with ixazomib did not have an adverse impact on HRQoL.

Patient-Reported Outcome Measures in Atopic Dermatitis and Chronic Hand Eczema in Adults.

Patient-reported outcome measures (PROMs) provide an important complement to physician-assessed clinical outcome measures in dermatologic diseases such as atopic dermatitis (AD) and chronic hand eczema (CHE). AD and CHE are chronic and relapsing inflammatory skin conditions that often co-occur. While both diseases result in various signs and symptoms that are burdensome and can negatively affect patients' lives, there may be distinct differences in the signs, symptoms, burden, and health-related quality of life (HRQOL) impact of these diseases. The objective of this study was to identify and evaluate PROMs used in studies of AD and CHE. The aim was to explore the assessment of key symptoms and impacts, and identify any gaps in the measures in use. A structured review of the PubMed database was conducted to identify PROMs used or developed for use in AD or CHE. The Dermatology Life Quality Index (DLQI), the Pruritus/Itch Numeric Rating Scale (NRS), the Patient-Oriented Eczema Measure (POEM), and the Quality of Life in Hand Eczema Questionnaire (QOLHEQ) were identified and reviewed in detail. With these measures, the AD and CHE symptoms and impacts most commonly evaluated in the literature include dermatology-related HRQOL in the domains of symptoms and feelings, daily activities, leisure, work and school, personal relationships, and adverse effects; pruritus; sleep disturbance; AD-specific symptoms (dryness, itching, flaking, cracking, bleeding, and weeping/oozing); and CHE-specific symptoms (pain, itch, fissuring, redness, bleeding, and dryness). A review of regulatory labels of drugs approved for AD by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) found that, among the four measures reviewed, the Pruritus NRS was included in the FDA and EMA labels for dupilumab, the DLQI was included in the EMA labels for dupilumab and tacrolimus, and the POEM was included in the EMA label for dupilumab. Key symptoms of AD (e.g. itching, flaking, cracking) and CHE (e.g. pain, itching, fissuring) are increasingly being assessed with PROMs; however, primary endpoints in clinical trials are often based on clinician-reported outcome measures. As therapeutic strategies in dermatology are targeted at specific dermatologic symptoms and diseases affecting specific sites (e.g. CHE), future research should explore patients' experiences with these symptoms and sites and the changes with treatment that are most meaningful to them.

A Review of Patient-Reported Outcomes Labeling for Oncology Drugs Approved by the FDA and the EMA (2012-2016).

OBJECTIVES: To compare US Food and Drug Administration (FDA) and European Medicines Agency (EMA) labeling for evidence based on patient-reported outcomes (PROs) of new oncology treatments approved by both agencies. METHODS: Oncology drugs and indications approved between 2012 and 2016 by both the FDA and the EMA were identified. PRO-related language and analysis reported in US product labels and drug approval packages and EMA summaries of product characteristics were compared for each indication. RESULTS: In total, 49 oncology drugs were approved for a total of 64 indications. Of the 64 indications, 45 (70.3%) included PRO data in either regulatory submission. No FDA PRO labeling was identified. PRO language was included in the summary of product characteristics for 21 (46.7%) of 45 indications. European Organisation for Research and Treatment of Cancer and Functional Assessment of Cancer Therapy measures were used frequently in submissions. FDA's comments suggest that aspects of study design (eg, open labels) or the validity of PRO measures was the primary reason for the lack of labeling based on PRO endpoints. Both agencies identified missing PRO data as problematic for interpretation. CONCLUSIONS: During this time period, the FDA and the EMA used different evidentiary standards to assess PRO data from oncology studies, with the EMA more likely to accept data from open-label studies and broad concepts such as health-related quality of life. An understanding of the key differences between the agencies may guide sponsor PRO strategy when pursuing labeling. Patient-focused proximal concepts are more likely than distal concepts to receive positive reviews.

Measurement Equivalence of Patient-Reported Outcome Measures Migrated to Electronic Formats: A Review of Evidence and Recommendations for Clinical Trials and Bring Your Own Device.

A growing number of clinical trials employ electronic media, in particular smartphones and tablets, to collect patient-reported outcome data. This is driven by the ubiquity of the technology, and an increased awareness of associated improvements in data integrity, quality and timeliness. Despite this, there remains a lingering question relating to the measurement equivalence of an instrument when migrated from paper to a screen-based format. As a result, researchers often must provide evidence demonstrating the measurement equivalence of paper and electronic versions, such as that recommended by the ISPOR ePRO Good Research Practices Task Force. In the last decade, a considerable body of work has emerged that overwhelmingly supports the measurement equivalence of instruments using screen-based electronic formats. Our review of key works derives recommendations on evidence needed to support electronic implementation. We recommend application of best practice recommendations is sufficient to conclude measurement equivalence with paper PROMs. In addition, we recommend that previous usability evidence in a representative group is sufficient, as opposed to per-study testing. Further, we conclude that this also applies to studies using multiple screen-based devices, including bring-your-own-device, if a minimum device specification can be ensured and the instrument is composed of standard response scale types.