Accelerating development of scientific evidence for medical products within the existing US regulatory framework

Sherman, Rachel E.; Davies, Kathleen M.; Robb, Melissa A.; Hunter, Nina L.; Califf, Robert M.

doi:10.1038/nrd.2017.25

Cited by 53 publications

(47 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, a recent review of pharmaceutical regulatory approvals found that, between 1999 and 2014, 76 drug approvals for indications were granted without evidence from RCTs [ 3 ]. The traditional RCT-based research evidence paradigm is being challenged by the establishment of accelerated regulatory pathways, a shift towards continuous development of clinical data with the integration of comprehensive information into ‘Big Data’, and the targeting of smaller patient populations through precision medicine, or development for orphan and ‘super-orphan’ indications [ 4 ]. The EMA’s guidance on adaptive pathways is taking this discussion to the next level.…”

Section: The Ebm Triad In Regulatory Decision Makingmentioning

confidence: 99%

Different Weights of the Evidence-Based Medicine Triad in Regulatory, Health Technology Assessment, and Clinical Decision Making

Schlegl¹,

Ducournau

Ruof³

2017

Pharm Med

View full text Add to dashboard Cite

Evidence-based medicine (EBM) is defined as a systematic approach to clinical problem solving by the integration of best research evidence with real-world clinical expertise and patient values. Since those early days, decision requirements expanded from patient-centric clinical decision making to a population-based view including regulatory health technology assessments (HTAs). Regulatory bodies mainly rely on the totality of research evidence, which includes preclinical and all available clinical data. HTA bodies primarily focus on clinical data with a strong preference for comparative data from randomized controlled clinical trials (RCTs). Conversely, bedside clinical decisions are largely driven by real-world clinical expertise, which takes into account the individual patients’ preferences, as well as the availability of supportive research evidence. While the focus on research evidence is a typical feature of the early part of the adoption curve for innovative technologies, HTA decision makers need to ensure that clinical expertise is also appropriately included in their decisions, in order to avoid beneficial medications from being not available to patients.

show abstract

Section: The Ebm Triad In Regulatory Decision Makingmentioning

confidence: 99%

Different Weights of the Evidence-Based Medicine Triad in Regulatory, Health Technology Assessment, and Clinical Decision Making

Schlegl¹,

Ducournau

Ruof³

2017

Pharm Med

View full text Add to dashboard Cite

show abstract

“…6,7 FDA encourages a flexible approach to trial design, prioritizing efficiency while also considering disease severity and rarity and degree of unmet need. 8 However, research in chronic diseases lags oncology and rare-disease specialties in applying novel methods.…”

Section: Cross-disciplinary Themesmentioning

confidence: 99%

The FDA and the State of Chronic Diseases: Cardiovascular, Endocrine, Pulmonary, and Renal Diseases

Fiuzat¹,

Mp²,

Gad³

et al. 2018

Preprint

View full text Add to dashboard Cite

Despite needs for new therapies and improvements in existing approaches in cardiovascular, pulmonary, endocrine, and renal disease, investment in these areas is lagging relative to other specialties. This article summarizes a meeting of key stakeholders of U.S. Food and Drug Administration (FDA) officials, representatives from academia, national organizations, and patients and caregivers. The purpose was to identify and discuss high-priority issues, establish areas of common interest, and explore opportunities for collaboration. During the meeting (September 2016), the construct of a “multimorbidity continuum” emerged, in which chronic diseases are understood as their effects on the whole rather than individual organ systems. Cross-disciplinary priorities included: 1) the need to generate greater high-quality evidence at lower cost; 2) the imperative to develop and implement patient-centered approaches to clinical investigations; 3) the importance of trial participation in under-represented populations, particularly with comorbid conditions, and 4) the need for progress in tobacco regulation. Representatives from each therapeutic area reported on their consensus priorities, and FDA representatives discussed the agency’s role in facilitating broader approaches to therapeutic development and evaluation of disease as linked across organ systems rather than in isolation, and emphasized the importance of patient engagement, collaboration and communication across stakeholders.

show abstract

“…[43] Although RWE has been instrumental as a primary evidence base for delayed cardiac effects of cancer therapy, its feasibility as an operational means to realize a more iterative and interconnected healthcare system at large is less clear. The means to integrate RWE as a complement to regulatory safety evaluation via randomized controlled trials (RCTs) and/or as a means of generating novel efficacy, safety, or use information for marketed drugs remains uncertain [40][41][42]. For example, Sherman et al (2017) cite the potential for RWE (e.g., postmarket surveillance or postmarket trials) to help refine dose-setting, subpopulation identification, and long-term safety considerations for novel cancer therapeutics that receive expedited initial approval.…”

Section: Data Sources and Driversmentioning

confidence: 99%

“…The cancer community at large is actively exploring opportunities to leverage this type of approach across broad cancer therapy classes and patient demographics. These efforts seek to use RWE in relation to a marketed drug or set of therapeutic approaches to promote a "learning healthcare system" (LHS) in the United States [40][41][42]. The LHS concept, initiated by the Institute of Medicine in the early 2000s, promotes the generation of "the best evidence and to apply that evidence to the healthcare choices that each patient and provider make in collaboration; to drive the process of discovery as a natural outgrowth of patient care; and to ensure innovation, quality, safety, and value in health care."…”

Section: Data Sources and Driversmentioning

confidence: 99%

Do current approaches to assessing therapy related adverse events align with the needs of long-term cancer patients and survivors?

Pettit

Kirch

2018

Cardio-Oncology

View full text Add to dashboard Cite

The increasing efficacy of cancer therapeutics means that the timespan of cancer therapy administration is undergoing a transition to increasingly long-term settings. Unfortunately, chronic therapy-related adverse health events are an unintended, but not infrequent, outcome of these life-saving therapies. Historically, the cardio-oncology field has evolved as retrospective effort to understand the scope, mechanisms, and impact of treatment-related toxicities that were already impacting patients. This review explores whether current systemic approaches to detecting, reporting, tracking, and communicating AEs are better positioned to provide more proactive or concurrent information to mitigate the impact of AE's on patient health and quality of life. Because the existing tools and frameworks for capturing these effects are not specific to cardiology, this study looks broadly at the landscape of approaches and assumptions. This review finds evidence of increasing focus on the provision of actionable information to support long-term health and quality of life for survivors and those on chronic therapy. However, the current means to assess and support the impact of this burden on patients and the healthcare system are often of limited relevance for an increasingly long-lived survivor and patient population.

show abstract

Accelerating development of scientific evidence for medical products within the existing US regulatory framework

Cited by 53 publications

References 4 publications

Different Weights of the Evidence-Based Medicine Triad in Regulatory, Health Technology Assessment, and Clinical Decision Making

Different Weights of the Evidence-Based Medicine Triad in Regulatory, Health Technology Assessment, and Clinical Decision Making

The FDA and the State of Chronic Diseases: Cardiovascular, Endocrine, Pulmonary, and Renal Diseases

Do current approaches to assessing therapy related adverse events align with the needs of long-term cancer patients and survivors?

Contact Info

Product

Resources

About