Accelerating evidence generation: Addressing critical challenges and charting a path forward.

Efficient evidence generation to assess the clinical and economic impact of medical therapies is critical amid rising healthcare costs and aging populations. However, drug development and clinical trials remain far too expensive and inefficient for all stakeholders. On October 25-26, 2023, the Duke Clinical Research Institute brought together leaders from academia, industry, government agencies, patient advocacy, and nonprofit organizations to explore how different entities and influencers in drug development and healthcare can realign incentive structures to efficiently accelerate evidence generation that addresses the highest public health needs.

Morbidity of SARS-CoV-2 in the evolution to endemicity and in comparison with influenza.

Background: There are three possible SARS-CoV-2 post-pandemic scenarios: (i) ongoing severity, (ii) influenza-like severity, and (iii) a transition to an endemic disease with lesser morbidity similar to that of other human coronaviruses.

Methods: To assess a possible evolution of the pandemic under the three scenarios, we use data from the US National Covid Cohort Collaborative, CDC COVID-NET, and CDC Fluview and from the WastewaterSCAN Dashboard. We include influenza disease and treatment response as benchmark.

A Systematic Review and Mixed Treatment Comparison of Pharmaceutical Interventions for Multiple Sclerosis.

Background: Since 2010, 27 mixed-treatment comparisons (MTCs) of disease-modifying therapies (DMTs) for multiple sclerosis have been published. However, there has been continued evolution in the field of MTCs. Additionally, limitations in methodological approach and reporting transparency, even in the most recent publications, makes interpretation and comparison of existing studies difficult.

Overview of Differences and Similarities of Published Mixed Treatment Comparisons on Pharmaceutical Interventions for Multiple Sclerosis.

Introduction: Mixed treatment comparisons (MTCs) are increasingly important in the assessment of the benefit-risk profile of pharmaceutical treatments for relapsing-remitting multiple sclerosis (RRMS). Interpretation of MTCs requires a clear understanding of the methods of analysis and population studied. The objectives of this work were to compare MTCs of pharmaceutical treatments for RRMS, including a detailed description of differences in populations, treatments assessed, methods used and findings; and to discuss key considerations when conducting an MTC.

Patient and physician preferences for multiple sclerosis treatments in Germany: A discrete-choice experiment study.

Objective: To assess heterogeneity in patient and physician preferences for multiple sclerosis treatment features and outcomes via a discrete-choice experiment.

Method: Patients with self-reported multiple sclerosis and treating physicians participated in an online discrete-choice experiment. Patients, each considering a better or worse reference condition, and physicians, each considering two patient profiles, chose between hypothetical treatment profiles defined by seven attributes with varying levels: years until disability progression, number of relapses in the decade, mode of administration, dosing frequency, and risks of mild, moderate, and severe side effects.

PREFERENCES OF PATIENTS WITH MULTIPLE SCLEROSIS FOR ATTRIBUTES OF INJECTABLE MULTIPLE SCLEROSIS TREATMENTS IN THE UNITED KINGDOM AND FRANCE.

Objectives: Adherence to injectable disease-modifying treatments in patients with multiple sclerosis (MS) impacts outcomes and can be influenced by perceptions of treatment efficacy, side effects, injection frequency, and the duration of injection. This study aimed to quantify preferences for selected attributes of injectable treatments among individuals with MS in the United Kingdom and France.

Methods: Respondents with a self-reported diagnosis of MS completed an online discrete-choice-experiment survey, consisting of a series of treatment-choice questions.

Measuring the impact of multiple sclerosis: Enhancing the measurement performance of the Multiple Sclerosis Impact Scale (MSIS-29) using Rasch Measurement Theory (RMT).

Background: Study objectives were to evaluate the Multiple Sclerosis Impact Scale (MSIS-29) and explore an optimized scoring structure based on empirical post-hoc analyses of data from the Phase III ADVANCE clinical trial.

Methods: ADVANCE MSIS-29 data from six time-points were analyzed in a sample of patients with relapsing-remitting multiple sclerosis (RRMS). Rasch Measurement Theory (RMT) analysis was undertaken to examine three broad areas: sample-to-scale targeting, measurement scale properties, and sample measurement validity.

Peginterferon beta-1a reduces disability worsening in relapsing-remitting multiple sclerosis: 2-year results from ADVANCE.

Background: In the pivotal phase III 2-year ADVANCE study, subcutaneous peginterferon beta-1a 125 mcg every 2 weeks demonstrated significant improvements in clinical outcomes, including disability endpoints, in patients with relapsing-remitting multiple sclerosis (RRMS). Here, we aim to further evaluate disability data from ADVANCE, and explore associations between confirmed disability progression (CDP), functional status, and health-related quality of life (HRQoL).

Methods: In total, 1512 patients were randomized to placebo or peginterferon beta-1a 125 mcg every 2 or 4 weeks.

Identification of Key Cost Generating Events for Idiopathic Pulmonary Fibrosis: A Systematic Review.

Background: Idiopathic pulmonary fibrosis (IPF) is an incurable, debilitating disease which impairs lung function and eventually leads to death. Currently, there is a lack of effective modifying therapies and treatments for IPF as the underlying epidemiological mechanism is not clearly understood. This leads to difficulty in diagnosing and managing IPF, which results in a high incurment of disease-associated cost.

A discrete-choice experiment to determine patient preferences for injectable multiple sclerosis treatments in Germany.

Objectives: The aim of this study was to assess the relative importance of features of a hypothetical injectable disease-modifying treatment for patients with multiple sclerosis using a discrete-choice experiment.

Methods: German residents at least 18 years of age with a self-reported physician diagnosis of multiple sclerosis completed a 25-30 minute online discrete-choice experiment. Patients were asked to choose one of two hypothetical injectable treatments for multiple sclerosis, defined by different levels of six attributes (disability progression, the number of relapses in the next 4 years, injection time, frequency of injections, presence of flu-like symptoms, and presence of injection-site reactions).

Cost-effectiveness analysis of peginterferon beta-1a compared with interferon beta-1a and glatiramer acetate in the treatment of relapsing-remitting multiple sclerosis in the United States.

Objective Peginterferon beta-1a 125 mcg, administered subcutaneously (SC) every 2 weeks, a new disease-modifying therapy (DMT) for relapsing-remitting multiple sclerosis (RRMS), was approved by the US Food and Drug Administration in 2014. This study assesses the cost-effectiveness of peginterferon beta-1a vs interferon beta-1a (44 mcg SC 3 times per week) and glatiramer acetate (20 mg SC once-daily) in the treatment of RRMS from the perspective of a US payer over 10 years. Methods A Markov cohort economic model was developed for this analysis.

Patient Preferences for Injectable Treatments for Multiple Sclerosis in the United States: A Discrete-Choice Experiment.

Background And Objective: Patients' perceptions and experiences of medication efficacy, medication adverse events, dosing frequency, and dosing complexity have been found to influence adherence to injectable disease-modifying treatments (DMTs) in patients with multiple sclerosis (MS). The aim of this study was to quantify patient preferences for features of injectable DMTs for MS.

Methods: Adult patients in the United States (US) with a self-reported diagnosis of MS completed an online discrete-choice experiment survey to assess preference for a number of features of a hypothetical injectable DMT.

A Network Meta-Analysis of Efficacy and Evaluation of Safety of Subcutaneous Pegylated Interferon Beta-1a versus Other Injectable Therapies for the Treatment of Relapsing-Remitting Multiple Sclerosis.

Subcutaneous pegylated interferon beta-1a (peginterferon beta-1a [PEG-IFN]) 125 μg every two or four weeks has been studied in relapsing-remitting multiple sclerosis (RRMS) patients in the pivotal Phase 3 ADVANCE trial. In the absence of direct comparative evidence, a network meta-analysis (NMA) was conducted to provide an indirect assessment of the relative efficacy, safety, and tolerability of PEG-IFN versus other injectable RRMS therapies. Systematic searches were conducted in MEDLINE, Embase, and the Cochrane Library, and conference proceedings from relevant annual symposia were hand-searched.

A comparison of two experimental design approaches in applying conjoint analysis in patient-centered outcomes research: a randomized trial.

Background: While the application of conjoint analysis and discrete-choice experiments in health are now widely accepted, a healthy debate exists around competing approaches to experimental design. There remains, however, a paucity of experimental evidence comparing competing design approaches and their impact on the application of these methods in patient-centered outcomes research.

Objectives: Our objectives were to directly compare the choice-model parameters and predictions of an orthogonal and a D-efficient experimental design using a randomized trial (i.

Decision-making criteria among national policymakers in five countries: a discrete choice experiment eliciting relative preferences for equity and efficiency.

Background: Worldwide, there is a need for formalization of the priority setting processes in health. Recent research has used the term multicriteria decision analysis for methods that systematically include preferences for both equity and efficiency. The present study compares decision-makers' preferences at the country level for a set of equity and efficiency criteria according to a multicriteria decision analysis framework.

Can patients diagnosed with schizophrenia complete choice-based conjoint analysis tasks?

Background: Schizophrenia is a severe mental illness associated with hallucinations, delusions, apathy, poor social functioning, and impaired cognition. Researchers and funders have been hesitant to focus efforts on treatment preferences of patients with schizophrenia because of the perceived cognitive burden that research methods, such as conjoint analysis, place on them.

Objective: The objective of this study was to test if patients diagnosed with schizophrenia were able to complete a choice-based conjoint analysis (often referred to as discrete-choice experiments) and to test if meaningful trade-offs were being made.

A discrete-event simulation of smoking-cessation strategies based on varenicline pivotal trial data.

Background: Smoking is the leading cause of preventable death in the US. While one in five individuals smoke, and 70% of these indicate a desire to quit, <5% of unaided quit attempts succeed. Cessation aids can double or triple the odds of successfully quitting.

Identifying patient-relevant endpoints among individuals with schizophrenia: an application of patient-centered health technology assessment.

Objectives: Schizophrenia imposes a great burden on society, and while evaluation should play an important role in informing society's efforts to alleviate these burdens, it is unclear what "endpoints" should be chosen as the objective of such analyses. The objectives of the study were to elicit endpoints directly from patients with schizophrenia, to ascertain whether patients are sufficiently cognoscente to express what endpoints are and are not important to them and to rank the relevant endpoints.

Methods: We applied principles of patient-centered health technology assessment to identify and value endpoints from the patient's perspective.

Things are Looking up Since We Started Listening to Patients: Trends in the Application of Conjoint Analysis in Health 1982-2007.

Clinical and healthcare decision makers have repeatedly endorsed patient-centered care as a goal of the health system. However, traditional methods of evaluation reinforce societal views, and research focusing on views of patients is often referred to as 'soft science.' Conjoint analysis presents a scientifically rigorous research tool that can be used to understand patient preferences and inform decision making.