Framework of the strengths and challenges of clinically integrated trials: An expert panel report.

The limitations of the explanatory clinical trial framework include the high expense of implementing explanatory trials, restrictive entry criteria for participants, and redundant logistical processes. These limitations can result in slow evidence generation that is not responsive to population health needs, yielding evidence that is not generalizable. Clinically integrated trials, which integrate clinical research into routine care, represent a potential solution to this challenge and an opportunity to support learning health systems. The operational and design features of clinically integrated trials include a focused scope, simplicity in design and requirements, the leveraging of existing data structures, and patient participation in the entire trial process. These features are designed to minimize barriers to participation and trial execution and reduce additional research burdens for participants and clinicians alike. Broad adoption and scalability of clinically integrated trials are dependent, in part, on continuing regulatory, healthcare system, and payer support. This analysis presents a framework of the strengths and challenges of clinically integrated trials and is based on a multidisciplinary expert "Think Tank" panel discussion that included representatives from patient populations, academia, non-profit funding agencies, the U.S. Food and Drug Administration, and industry.

Real-world experiences with generating real-world evidence: Case Studies from PCORI's pragmatic clinical Studies program.

BACKGROUND: Over the last decade, randomized studies evaluating outcomes of health care interventions conducted in real-world settings-often termed "pragmatic trials"-have come to be seen as an important means of obtaining relevant, actionable evidence to guide health care decisions. Despite extensive writing on methodological considerations in pragmatic trial design, limited information exists regarding the practical and logistical challenges encountered in carrying out rigorous randomized evaluations in highly representative, real-world contexts. METHODS: The Patient Centered Outcomes Research Institute (PCORI) convened an expert panel in 2017 to examine common tradeoffs in study design and implementation through 3 "case studies" of in-progress, PCORI-funded pragmatic trials. This paper summarizes the findings of this panel, using the 3 examples to illustrate common implementation challenges encountered in pragmatic trials. RESULTS: Investigators aimed to generate highly generalizable findings that could address real-world clinical decisions; however, practical considerations required that each study incorporate traditionally "explanatory" elements to achieve a "fit-for-purpose" approach to design and implementation. Within individual studies, efforts to balance pragmatic versus explanatory perspectives often involved multiple, diverse aspects of trial design and implementation, and the aspects of design and implementation where investigators reported encountering such tradeoffs varied across the three cases we examined. CONCLUSIONS: Efforts to generate rigorous evidence that is generalizable to "real-world" practice require continuous and iterative efforts to balance "pragmatic" and "explanatory" perspectives. In each study examined, these tradeoffs were guided both by an overriding effort to maintain pragmatism and practical considerations that varied depending on the research question and study context.

Patient-centered priorities for improving medication management and adherence.

OBJECTIVE: The Centers for Education and Research on Therapeutics convened a workshop to examine the scientific evidence on medication adherence interventions from the patient-centered perspective and to explore the potential of patient-centered medication management to improve chronic disease treatment. METHODS: Patients, providers, researchers, and other stakeholders (N = 28) identified and prioritized ideas for future research and practice. We analyzed stakeholder voting on priorities and reviewed themes in workshop discussions. RESULTS: Ten priority areas emerged. Three areas were highly rated by all stakeholder groups: creating tools and systems to facilitate and evaluate patient-centered medication management plans; developing training on patient-centered prescribing for providers; and increasing patients' knowledge about medication management. However, priorities differed across stakeholder groups. Notably, patients prioritized using peer support to improve medication management while researchers did not. CONCLUSION: Engaging multiple stakeholders in setting a patient-centered research agenda and broadening the scope of adherence interventions to include other aspects of medication management resulted in priorities outside the traditional scope of adherence research. PRACTICE IMPLICATIONS: Workshop participants recognized the potential benefits of patient-centered medication management but also identified many challenges to implementation that require additional research and innovation.

Risk minimization practices for pregnancy prevention: understanding risk, selecting tools.

According to the March of Dimes, approximately 4% (1/28) of babies are born in the US each year with a birth defect. For the majority of birth defects the etiology is unknown, although chemicals, including drug exposures, probably account for less than 1% of all birth defects. The identification of potential human teratogenicity during drug development is important because drug-induced adverse fetal effects are potentially preventable with the application of risk assessment strategies and risk minimization tools and programs to minimize risk of pregnancy exposure while preserving access to drug benefits; risk assessment and risk minimization together comprise risk management. It is important that risk minimization programs intended to limit fetal exposure use a consistent approach and are tailored to the product-specific risk concerns in order to optimize the benefit-risk balance for a particular drug. This paper highlights general considerations in developing specific risk minimization programs to prevent fetal drug exposure including the relative advantages and disadvantages of each strategy.

Changes in isotretinoin prescribing before and after implementation of the System to Manage Accutane Related Teratogenicity (SMART) risk management program.

PURPOSE: To assess changes in isotretinoin prescribing following the implementation of the System to Manage Accutane Related Teratogenicity (SMART) risk management program. METHODS: Using nationally representative commercial data resources on prescription drug dispensing patterns, surveys of office-based physician practices, and a large, claims database from a pharmacy benefits manager (PBM), we examined the total number of isotretinoin prescriptions (new and refill), prescriber speciality, and patient characteristics (age, gender, severity of acne indication) in the year before (April 2001-March 2002) and the year following (April 2002-March 2003) implementation of the SMART program. RESULTS: In the 12-months prior to SMART, 1 508 000 prescriptions were dispensed for isotretinoin, declining approximately 23% to 1 160 000 prescriptions in the year following SMART. There was little or no change in prescriber specialty, severity of acne, and patient age and gender. CONCLUSION: SMART may have lead to a decrease in isotretinoin prescriptions. Further research is needed to determine whether the reduced number of isotretinoin prescriptions reflects appropriate use or inhibited use resulting in loss of access to the product's benefits.