Precision medicine at the academic-industry interface

Silva, Patrick J.; Ramos, Kenneth S.

doi:10.1016/b978-0-12-819178-1.00053-8

Cited by 2 publications

(3 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is a more pragmatic approach to pilot and assess RCT feasibility or as an alternative form of evidence, by enabling the use of existing data instead of the costs of enrolling a participating control cohort. Pooling data is an approach that has been used confront sample size challenges in single health systems but data governance barriers across organizational barriers make this approach laborious (49,51,52).…”

Section: Discussion Of Limitationsmentioning

confidence: 99%

“…The population paradox is defined as understanding the clinical relevance of molecular differences within a population. The population paradox enables the use of clinicogenomics databases for therapeutic development, clinical trials design, and therapeutic decision making for individualized medical care (49)(50)(51)(52). Evidence gaps, however, remain for the use of NGS with RWE in health insurance coverage decision-making with the exception of pharmacogenomics testing, suspected pediatric genetic disorders, and oncology (48).…”

Section: Regulatory Guidancementioning

confidence: 99%

“…Medical paradigms are changing. The intended use and labeling of therapeutics are increasingly agnostic of medical subspecialty, target tissue or organ, or pathologic characterization (56). Inter-connecting biological pathways now define risks for the development of disease or a disease process, and the corresponding therapeutic strategy.…”

Section: External Control Armmentioning

confidence: 99%

See 2 more Smart Citations

External control arms: COVID-19 reveals the merits of using real world evidence in real-time for clinical and public health investigations

et al. 2023

Self Cite

View full text Add to dashboard Cite

Randomized controlled trials are considered the ‘gold standard’ to reduce bias by randomizing patients to an experimental intervention, versus placebo or standard of care cohort. There are inherent challenges to enrolling a standard of care or cohorts: costs, site engagement logistics, socioeconomic variability, patient willingness, ethics of placebo interventions, cannibalizing the treatment arm population, and extending study duration. The COVID-19 pandemic has magnified aspects of constraints in trial recruitment and logistics, spurring innovative approaches to reducing trial sizes, accelerating trial accrual while preserving statistical rigor. Using data from medical records and databases allows for construction of external control arms that reduce the costs of an external control arm (ECA) randomized to standard of care. Simultaneously examining covariates of the clinical outcomes in ECAs that are being measured in the interventional arm can be particularly useful in phase 2 trials to better understand social and genetic determinants of clinical outcomes that might inform pivotal trial design. The FDA and EMA have promulgated a number of publicly available guidance documents and qualification reports that inform the use of this regulatory science tool to streamline clinical development, of phase 4 surveillance, and policy aspects of clinical outcomes research. Availability and quality of real-world data (RWD) are a prevalent impediment to the use of ECAs given such data is not collected with the rigor and deliberateness that characterizes prospective interventional control arm data. Conversely, in the case of contemporary control arms, a clinical trial outcome can be compared to a contemporary standard of care in cases where the standard of care is evolving at a fast pace, such as the use of checkpoint inhibitors in cancer care. Innovative statistical methods are an essential aspect of an ECA strategy and regulatory paths for these innovative approaches have been navigated, qualified, and in some cases published.

show abstract

Section: Discussion Of Limitationsmentioning

confidence: 99%

Section: Regulatory Guidancementioning

confidence: 99%

Section: External Control Armmentioning

confidence: 99%

See 1 more Smart Citation

External control arms: COVID-19 reveals the merits of using real world evidence in real-time for clinical and public health investigations

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

Health equity innovation in precision medicine: data stewardship and agency to expand representation in clinicogenomics

Silva,

Rahimzadeh,

Powell

et al. 2024

Health Res Policy Sys

View full text Add to dashboard Cite

Most forms of clinical research examine a very minute cross section of the patient journey. Much of the knowledge and evidence base driving current genomic medicine practice entails blind spots arising from underrepresentation and lack of research participation in clinicogenomic databases. The flaws are perpetuated in AI models and clinical practice guidelines that reflect the lack of diversity in data being used. Participation in clinical research and biobanks is impeded in many populations due to a variety of factors that include knowledge, trust, healthcare access, administrative barriers, and technology gaps. A recent symposium brought industry, clinical, and research participants in clinicogenomics to discuss practical challenges and potential for new data sharing models that are patient centric and federated in nature and can address health disparities that might be perpetuated by lack of diversity in clinicogenomic research, biobanks, and datasets. Clinical data governance was recognized as a multiagent problem, and governance practices need to be more patient centric to address most barriers. Digital tools that preserve privacy, document provenance, and enable the management of data as intellectual property have great promise. Policy updates realigning and rationalizing clinical data governance practices are warranted.

show abstract

Precision medicine at the academic-industry interface

Cited by 2 publications

References 66 publications

External control arms: COVID-19 reveals the merits of using real world evidence in real-time for clinical and public health investigations

External control arms: COVID-19 reveals the merits of using real world evidence in real-time for clinical and public health investigations

Health equity innovation in precision medicine: data stewardship and agency to expand representation in clinicogenomics

Contact Info

Product

Resources

About