Core Clinical Data Elements for Cancer Genomic Repositories: A Multi-stakeholder Consensus.

The Center for Medical Technology Policy and the Molecular Evidence Development Consortium gathered a diverse group of more than 50 stakeholders to develop consensus on a core set of data elements and values essential to understanding the clinical utility of molecularly targeted therapies in oncology.

Development of the coreHEM mental health patient-reported outcome measure - A novel mental health outlook measure for people with haemophilia.

INTRODUCTION: Currently, no quality-of-life instrument exists that captures the full experience of the mental health outlook (MHO), a coreHEM core outcome, in people with haemophilia, including the potential transformational experience of receiving gene therapy. AIM: To describe the methods used to develop a content validated patient-reported outcome measure (PROM) that measures MHO for people with haemophilia. METHODS: A conceptual framework, developed from a literature/evidence review, was used to create an interview guide and draft a questionnaire. Males aged 15 or older with severe/moderate haemophilia were eligible to participate in concept elicitation or cognitive debriefing interviews. The conceptual framework was refined based on a thematic analysis of concept elicitation interviews and PROM items were developed from the conceptual framework. Cognitive debriefing sessions that prioritised relevance and understanding of the PROM were held in two rounds; items were updated iteratively. RESULTS: A conceptual framework with five domains (stigma, anxiety, depression, life interference and identity) was constructed from over 300 identified MHO concepts. Fifty-three participants took part in interviews. After 32 concept elicitation interviews, the framework was updated by including eight new sub-concepts and eliminating two. Updates to the questionnaire included items added or removed and improved wording. The final coreHEM MHO PROM has 26 questions in two sections (general mental health associated with haemophilia, and a gene therapy section). CONCLUSIONS: The instrument is content-validated and can be used as an exploratory outcome. MHO scores can be measured and compared to give more insight into patient quality of life.

Generating and evaluating evidence of the clinical utility of molecular diagnostic tests in oncology.

PURPOSE: Enthusiasm for molecular diagnostic (MDx) testing in oncology is constrained by the gaps in required evidence regarding its impact on patient outcomes (clinical utility (CU)). This effectiveness guidance document proposes recommendations for the design and evaluation of studies intended to reflect the evidence expectations of payers, while also reflecting information needs of patients and clinicians. METHODS: Our process included literature reviews and key informant interviews followed by iterative virtual and in-person consultation with an expert technical working group and an advisory group comprising life-sciences industry experts, public and private payers, patients, clinicians, regulators, researchers, and other stakeholders. RESULTS: Treatment decisions in oncology represent high-risk clinical decision making, and therefore the recommendations give preference to randomized controlled trials (RCTs) for demonstrating CU. The guidance also describes circumstances under which alternatives to RCTs could be considered, specifying conditions under which test developers could use prospective-retrospective studies with banked biospecimens, single-arm studies, prospective observational studies, or decision-analytic modeling techniques that make a reasonable case for CU. CONCLUSION: Using a process driven by multiple stakeholders, we developed a common framework for designing and evaluating studies of the clinical validity and CU of MDx tests, achieving a balance between internal validity of the studies and the relevance, feasibility, and timeliness of generating the desired evidence.Genet Med 18 8, 780-787.

Proposed framework for patient-centered outcomes-based measures in alternative payment models.

OBJECTIVES: Alternative payment models (APMs) are part of a growing shift from volume-based, traditional fee-for-service payment models toward payment for value. To date, however, patients have been largely omitted from efforts to design new payment models. We sought to identify key characteristics of outcomes-based quality measures to inform future APMs that are more patient-centered. STUDY DESIGN: Using oncology as a learning case, we explored gaps in current APM quality measures, then engaged multiple stakeholders to identify and prioritize key characteristics of outcomes-based quality measures to guide future APM development. METHODS: We used a mixed-methods approach that consisted of (1) literature review, (2) key informant interviews, (3) stakeholder work group (involving group discussions and completion of an online prioritization survey), and (4) synthesis. RESULTS: Based on the lessons generated at each step of this exploratory project, we suggest a framework to guide deliberations among payers, providers, patients, and other APM stakeholders when selecting outcomes-based measures for future APMs or other value-based payment models. CONCLUSIONS: The proposed framework offers a stepping stone on the path to clinically meaningful, patient-centered, high-value care. Next steps may include a broader review of gaps in APM quality measures across multiple therapeutic areas, additional vetting from a more diverse group of stakeholders, or a formal consensus.

Increasing the Patient-Centeredness of Health Economics and Outcomes Research Through Patient Engagement in Core Outcome Set Development.

Core outcome sets (COS) are becoming increasingly popular in clinical research and can provide important inputs for further health economics and outcomes research (HEOR) studies. Use of standard, consistently reported outcomes can demonstrate and allow differentiation of the effectiveness and value of different treatments. Incorporating patient values during COS development increases the patient centeredness of evidence available across decision-making contexts. However, the approach to meaningful patient engagement in the COS process is evolving and poses both unique challenges and opportunities. We describe an approach to patient-centered COS development and discuss challenges and adaptations to improve engagement across COS projects. We provide examples from our experience in patient engagement for COS development using three completed COS projects. This approach includes patient engagement in terms of partnering with patient organizations, orientation and training, and the consensus process. Including COS in clinical development programs and HEOR will ensure that relevant, consistent outcomes are available for healthcare decision making and should result in faster access to high-value and novel therapies for patients. Patient-centered COS development increases the likelihood that further HEOR studies and decisions made using the COS are relevant to patients.

coreNASH: Multi-stakeholder Consensus on Core Outcomes for Decision Making About Nonalcoholic Steatohepatitis Treatment.

The increasing prevalence and burden of nonalcoholic steatohepatitis (NASH) has spurred the development of new treatments and a need to consider outcomes used for NASH treatment decision making. Development of a NASH core outcome set (COS) can help prioritize outcomes of highest importance by incorporating the perspectives from a variety of decision makers. coreNASH was an initiative to develop a COS for NASH using a modified Delphi consensus process with a multi-stakeholder voting panel. A candidate outcome list was created based on a literature review and key informant interviews. The candidate outcome list was then condensed and prioritized through three rounds of online voting and through discussion at an in-person meeting. Outcomes were retained or eliminated based on predetermined consensus criteria, which included special weighting of patients' opinions in the first two voting rounds. The coreNASH Delphi panel included 53 participants (7 patients, 10 clinicians and researchers, 7 health technology assessors, 22 industry representatives, 2 regulators, and 5 payers) who considered outcomes for two NASH-related COS: one for NASH without cirrhosis (F2-F3) and one for NASH with cirrhosis (F4). The initial candidate outcome list for both disease stages included 86 outcomes. The panel agreed on including two core outcomes for NASH without cirrhosis and nine core outcomes for NASH with cirrhosis in the COS. Conclusion: A consensus-based COS has been developed that can be used across the life cycle of NASH treatments. Outcomes included can contribute to decision making for regulatory, market access, and on-market decision making. Including the coreNASH COS in clinical development programs will facilitate improved comparisons and help decision makers assess the value of new products.

The increasing complexity of the core outcomes landscape.

In this project, we set out to identify ways to increase the uptake of core outcome sets in clinical research. In doing so, we uncovered a growing recognition, across many different health care sectors, of the need for common, relevant outcomes to improve the quality of decision-making. This has led to a plethora of projects, initiatives, and new organizations all intended to develop standardized outcomes and outcome measures for their particular fields. However, the standardized outcome sets developed across siloed initiatives do not carry over to other sectors, such as from research to quality of care. This trend has the potential to lead to confusion and unintended redundancies, as well as wasteful use of both financial and intellectual resources. Better communication and collaboration among different initiatives, and more deliberate alignments of initiative scopes, are needed to ensure a future paradigm in which standards align across contexts where possible and differ for understandable and transparent reasons.

Barriers to clinical adoption of next-generation sequencing: a policy Delphi panel's solutions.

AIM: Identify solutions to the most important policy barriers to the clinical adoption of next-generation sequencing. MATERIALS & METHODS: Four-round modified policy Delphi with a multistakeholder panel of 48 experts. The panel deliberated policy solutions to (previously reported) challenges deemed most important to address. RESULTS: The group advocated using consensus panels to promote consistency in payer policies and to standardize test reporting, and favored making genomic data-sharing a condition of regulatory clearance, certification, or accreditation processes. They were split on the role of US FDA. CONCLUSION: Panelists found common ground on solutions for health plan coverage policy consistency, data-sharing, and standardizing reporting, but were sharply divided on the role of the FDA in mitigating risks to patients.

Understanding practice-based research participation: The differing motivations of engaged vs. non-engaged clinicians in pragmatic clinical trials.

BACKGROUND/AIMS: Pragmatic clinical trials (PCTs) represent an increasingly used strategy for "real-world" trials. Successful PCTs typically require participation of community-based practices. However, community clinicians often have limited interest or experience in clinical research. Many barriers to practice-based research have been described, but possible motivations to participate among community practices not active in research have not been well explored. The tendency is for researchers to assume similar motivations and priorities across all candidate practices. This is not necessarily the case. A better understanding of the range of reasons clinicians might see for participating in pragmatic trials could be key to promoting this type of practice-based research. METHODS: Semi-structured interviews were conducted with 30 clinicians and staff members. Half of the interviewees had experience doing practice-based clinical trials and half did not. Individuals in these two groups were also diversified in terms of their practice size and location. Participants were asked about motivations and barriers to doing practice-based research in the context of a planned osteoporosis pragmatic clinical trial. Interviews were transcribed, coded, and analyzed. RESULTS: Barriers identified for both experienced and not-experienced clinicians and staff members included: a lack of time, increased paperwork, disruption to work flows, and concern over practice finances. Similar findings have been reported in the US, UK, Europe, and Australia. However, regarding positive motivations of practices to participate, we found systematic differences in attitude between research-engaged and research-naïve practices that have not been previously reported. The research-experienced group offered a greater number and variety of reasons to take part than the not-experienced group. While both groups expressed motivations related to patient care, clinicians and staff members experienced in practice-based clinical trials were much more likely to cite intellectual, professional, and societal benefits not envisioned by the other group. CONCLUSIONS: We conclude that clinicians not already participating in practice-based trials may have a narrower range of motivations than those already participating. The lack of a broader view of possible benefits to participation may also translate into more obdurate recruiting challenges. These results point to the need for recruitment, engagement, and messaging approaches differentially tailored to the needs and interests of non-participating practices.

Barriers to clinical adoption of next generation sequencing: Perspectives of a policy Delphi panel.

This research aims to inform policymakers by engaging expert stakeholders to identify, prioritize, and deliberate the most important and tractable policy barriers to the clinical adoption of next generation sequencing (NGS). A 4-round Delphi policy study was done with a multi-stakeholder panel of 48 experts. The first 2 rounds of online questionnaires (reported here) assessed the importance and tractability of 28 potential barriers to clinical adoption of NGS across 3 major policy domains: intellectual property, coverage and reimbursement, and FDA regulation. We found that: 1) proprietary variant databases are seen as a key challenge, and a potentially intractable one; 2) payer policies were seen as a frequent barrier, especially a perceived inconsistency in standards for coverage; 3) relative to other challenges considered, FDA regulation was not strongly perceived as a barrier to clinical use of NGS. Overall the results indicate a perceived need for policies to promote data-sharing, and a desire for consistent payer coverage policies that maintain reasonably high standards of evidence for clinical utility, limit testing to that needed for clinical care decisions, and yet also flexibly allow for clinician discretion to use genomic testing in uncertain circumstances of high medical need.

Futurescapes: evidence expectations in the USA for comparative effectiveness research for drugs in 2020.

AIM: Explore key factors influencing future expectations for the production of evidence from comparative effectiveness research for drugs in the USA in 2020 and construct three plausible future scenarios. MATERIALS & METHODS: Semistructured key informant interviews and three rounds of modified Delphi with systematic scenario-building methods. RESULTS & CONCLUSION: Most influential key factors were: health delivery system integration; electronic health record development; exploitation of very large databases and mixed data sources; and proactive patient engagement in research. The scenario deemed most likely entailed uneven development of large integrated health systems with pockets of increased provider risk for patient care, enhanced data collection systems, changing incentives to do comparative effectiveness research and new opportunities for evidence generation partnerships.

The future of comparative effectiveness and relative efficacy of drugs: an international perspective.

Drug development takes place in a global marketplace, albeit with the USA and EU markets currently dominating. In the USA, demands for comparative effectiveness research have gained traction against a backdrop of health delivery reform, while European stakeholders deliberate the role of relative effectiveness in health technology assessment, trying to reduce the duplication of effort by regulators and health technology assessment bodies. In both arenas, drug-makers are faced with mounting drug development costs, and uncertainty over the types of evidence acceptable for a growing list of stakeholders. This article reports and compares future scenarios for evidence expectations for drugs for the USA and EU in 2020. The similarities, differences, and joint implications of the scenarios are considered to create an view of future evidence generation for drugs developed for these markets.

Futurescapes: expectations in Europe for relative effectiveness evidence for drugs in 2020.

AIM: Explore key factors influencing future expectations for the production of evidence of relative effectiveness (RE) for drugs in Europe in 2020; construct three plausible future scenarios for RE evidence generation. MATERIALS & METHODS: Semi-structured key informant interviews and three rounds of modified Delphi to gather expert perspectives and develop future scenarios. RESULTS & CONCLUSION: Most influential factors were degree of regulator use of postmarketing authorization (postlaunch) efficacy studies and adaptive licensing; degree of pan-European health technology assessment body coordination in reviewing prelaunch evidence and demanding postlaunch studies; the nature of regulator - health technology assessment body interaction. The most likely scenario entailed some change with postlaunch regulatory studies driving the likely nature of RE evidence generated.

A translation table for patient-centered comparative effectiveness research: guidance to improve the value of research for clinical and health policy decision-making.

This article provides background and context for a series of papers stemming from a collaborative effort by Outcome Sciences, Inc., the National Pharmaceutical Council and the Center for Medical Technology Policy to use a stakeholder-driven process to develop a decision tool to select appropriate methods for comparative effectiveness research. The perceived need and origins of the 'translation table' concept for method selection are described and the legislative history and role of the Patient-Centered Outcomes Research Institute are reviewed. The article concludes by stressing the significance of this effort for future health services and clinical research, and the importance of consulting end-users--patients, providers, payers and policy-makers--in the process of defining research questions and approaches to them.

Incorporating stakeholder perspectives in developing a translation table framework for comparative effectiveness research.

This project used a stakeholder-driven process to understand the factors that drive the selection of study designs for comparative effectiveness research (CER). The project assembled a diverse stakeholder committee to explore the basis of a translation framework and gathered input through surveys, interviews and an in-person meeting. Stakeholders recommended different study designs for the CER topic areas and identified different outcomes as the most important outcomes to study in each area. During the discussions, stakeholders described a variety of factors that influenced their study design recommendations. The stakeholder activities resulted in the identification of several key themes, including the need to have a highly specific detailed research question before discussing appropriate designs and the need to use multiple studies, potentially of different designs, to address the CER topic areas. The insights and themes from this project may inform efforts to develop a translation table.

Informed Choice in Direct-to-Consumer Genetic Testing for Alzheimer and Other Diseases: Lessons from Two Cases.

Health-related direct-to-consumer (DTC) genetic testing has been a controversial practice. Especially problematic is predictive testing for Alzheimer disease (AD), since the disease is incurable, prevention is inconclusive, and testing does not definitively predict an individual's future disease status. In this paper, I examine two contrasting cases of subjects who learn through genetic testing that they have an elevated risk of developing AD later in life. In these cases, the subject's emotional response to the result is related to how well prepared she was for the real-life personal implications of possible test results. Analysis leads to the conclusion that when groups of health-related genetic tests are offered as packages by DTC companies, informed consumer choice is rendered impossible. Moreover, I argue, this marketing approach contravenes U.S. Federal Trade Commission policies for non-deceptive commercial communications. I conclude by suggesting ways to improve the prospects for informed consumer choice in DTC testing.