Paving the way for patient centricity in real-world evidence (RWE): Qualitative interviews to identify considerations for wider implementation of patient-reported outcomes in RWE generation.

Objectives: Real-world evidence (RWE) generation can be enhanced by including patient-reported outcomes (PROs). Methods for collecting and using PRO data in the real-world setting are currently underdeveloped and there is no international guidance specific to its use in this context. This study explored stakeholders' perspectives and needs for using PROs in RWE generation. Barriers, facilitators, and opportunities for wider use of PROs in real-world studies were also investigated. Methods: Online semi-structured interviews were conducted with international stakeholders: patients, patient advocates, regulators, payers, clinicians, academic researchers, and industry experts. Interviews were recorded, transcribed verbatim and analysed using NVivo 20. Thematic analysis was conducted based on the updated Consolidated Framework for Implementation Research (CFIR). Results: Twenty-three interviews were conducted. Participants confirmed that the use of PROs in RWE generation is not yet well established. Participants expressed a mixed level of confidence in the value of PROs collected in a real-world setting. Operational challenges associated with collecting routine PRO data to inform care delivery at the individual level (e.g., setting up infrastructure) need to be addressed. Methodological and other challenges (e.g., financing research) associated with collecting prospective de novo data in a real-world setting should be considered to facilitate PRO utilisation in real-world studies. Conclusions: Several opportunities and challenges were identified regarding the broader use of PROs in RWE research. Joint efforts from different stakeholders are needed to maximise PRO implementation, with consideration given to each stakeholders' specific needs (e.g., by developing good practices).

Systematic review of guidance for the collection and use of patient-reported outcomes in real-world evidence generation to support regulation, reimbursement and health policy.

BACKGROUND: Real-world evidence (RWE) plays an increasingly important role within global regulatory and reimbursement processes. RWE generation can be enhanced by the collection and use of patient-reported outcomes (PROs), which can provide valuable information on the effectiveness, safety, and tolerability of health interventions from the patient perspective. This systematic review aims to examine and summarise the available PRO-specific recommendations and guidance for RWE generation. METHODS AND FINDINGS: Medical Literature Analysis and Retrieval System Online, Excerpta Medica Database, and websites of selected organisations were systematically searched to identify relevant publications. 1,249 articles were screened of which 7 papers met the eligibility criteria and were included in the review. The included publications provided PRO-specific recommendations to facilitate the use of PROs for RWE generation and these were extracted and grouped into eight major categories. These included: (1) instrument selection, (2) participation and engagement, (3) burden to health care professionals and patients, (4) stakeholder collaboration, (5) education and training, (6) PRO implementation process, (7) data collection and management, and (8) data analysis and presentation of results. The main limitation of the study was the potential exclusion of relevant publications, due to poor indexing of the databases and websites searched. CONCLUSIONS: PROs may provide valuable and crucial patient input in RWE generation. Whilst valuable insights can be gained from guidance for use of PROs in clinical care, there is a lack of international guidance specific to RWE generation in the context of use for regulatory decision-making, reimbursement, and health policy. Clear and appropriate evidence-based guidance is required to maximise the potential benefits of implementing PROs for RWE generation. Unique aspects between PRO guidance for clinical care and other purposes should be differentiated. The needs of various stakeholder groups (including patients, health care professionals, regulators, payers, and industry) should be considered when developing future guidelines.

Implementation of patient-reported outcome measures in real-world evidence studies: Analysis of ClinicalTrials.gov records (1999-2021).

BACKGROUND: Real-world evidence (RWE) plays an increasingly important role within global regulatory and reimbursement processes. RWE generation can be enhanced by collecting and using patient-reported outcomes (PROs), which can provide valuable information on the effectiveness, safety, and tolerability of health interventions from the patient perspective. This analysis aims to examine and summarise the utilisation of patient-reported outcomes measures (PROMs) in real-world studies. METHODS: Descriptions of phase IV trials were downloaded on July 22, 2021 from the Clinicaltrials.gov database since its inception. An automated algorithm was built to detect trials utilising PROMs and composite measures including patient-reported components. Search terms were developed based on the PROQOLID database. RESULTS: Of 27,976 phase IV clinical trials posted on Clinicaltrials.gov between 1999 and July 2021, 21% and 4% used PROMs and composite measures, respectively. Recent years demonstrated a steady increase in the utilisation of PROMs in phase IV trials. CONCLUSIONS: The use of PROMs in phase IV trials seems to be lower than its use in earlier phases of clinical research. Increased uptake of PROMs in RWE studies can be facilitated in a number of ways including the development of standards for their collection, analysis and use.

The Budget Impact of Monoclonal Antibodies Used to Treat Metastatic Colorectal Cancer in Minas Gerais, Brazil.

INTRODUCTION: Biological medicines have increased the cost of cancer treatments, which also raises concerns about sustainability. In Brazil, three monoclonal antibodies (mAbs)-bevacizumab, cetuximab, and panitumumab-are indicated for the treatment of metastatic colorectal cancer (mCRC) but not currently funded by the Unified Health System (SUS). However, successful litigation has led to funding in some cases. OBJECTIVE: Our objective was to evaluate the budgetary impact of including the mAbs bevacizumab, cetuximab, and panitumumab in standard chemotherapy for the treatment of mCRC within the SUS of Minas Gerais (MG), Brazil. METHOD: A budget impact analysis of incorporating mAbs as first-line treatment of mCRC in MG was explored. The perspective taken was that of the Brazilian SUS, and a 5-year time horizon was applied. Data were collected from lawsuits undertaken between January 2009 and December 2016, and the model was populated with data from national databases and published sources. Costs are expressed in $US. RESULTS: In total, 351 lawsuits resulted in funding for first-line treatment with mAbs for mCRC. The three alternative scenarios analyzed resulted in cost increases of 348-395% compared with the reference scenario. The use of panitumumab had a budgetary impact of $US103,360,980 compared with the reference scenario over a 5-year time horizon, and bevacizumab and cetuximab had budgetary impacts of $US111,334,890 and 113,772,870, respectively. The use of the anti-epidermal growth factor receptor (EGFR) mAbs (cetuximab and panitumumab) is restricted to the approximately 41% of patients with KRAS mutations, so the best cost alternative for incorporation would be the combination of panitumumab and bevacizumab, with a cost of approximately $US106 million. CONCLUSION: These results highlight the appreciable costs for incorporating bevacizumab, cetuximab, and panitumumab into the SUS. Appreciable discounts are likely to be necessary before incorporation of these mAbs is approved.

Adult lifetime cost of hemophilia B management in the US: payer and societal perspectives from a decision analytic model.

AIMS: Hemophilia B (HB) is a rare congenital disorder characterized by bleeding-related complications which are managed by prophylactic or post-bleeding event ("on-demand") replacement of clotting factor IX (FIX). The standard of care for severe HB is life-long prophylaxis with standard half-life (SHL) or extended half-life (EHL) products given every 2-3 or 7-14 days, respectively. FIX treatment costs in the US have been investigated, but the lifetime costs of HB treatment have not been well characterized, particularly related to the impact of joint health deterioration and associated health resource utilization. We developed a decision-analytic model to explore outcomes, costs and underlying cost drivers associated with FIX treatment options over the lifetime of an adult with severe or moderately severe HB. MATERIALS AND METHODS: With participation from clinicians, health technology assessment specialists and patient advocates, a Markov model was constructed to estimate bleeding events and costs associated with health states including "bleed into joint", "bleed not into joint", "no bleed" and "death". Sub-models of joint health were based on 0, 1, or ≥2 areas of chronic joint damage. US third-party payer and societal perspectives were considered with a lifetime horizon; sensitivity analyses tested the robustness of primary findings. RESULTS: Total adult lifetime costs per patient with severe and moderately severe HB were $21,086,607 for SHL FIX prophylaxis, $22,987,483 for EHL FIX prophylaxis, and $20,971,826 for on-demand FIX treatment. For FIX prophylaxis, the cost of FIX treatment accounts for >90% of the total HB treatment costs. CONCLUSIONS: This decision analytic model demonstrated significant economic burden associated with the current HB treatment paradigm.