+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Considerations in the evaluation of surrogate endpoints in clinical trials: Summary of a National Institutes of Health Workshop



Considerations in the evaluation of surrogate endpoints in clinical trials: Summary of a National Institutes of Health Workshop



Controlled Clinical Trials 22(5): 485-502



We report on recommendations from a National Institutes of Health Workshop on methods for evaluating the use of surrogate endpoints in clinical trials, which was attended by experts in biostatistics and clinical trials from a broad array of disease areas. Recent advances in biosciences and technology have increased the ability to understand, measure, and model biological mechanisms; appropriate application of these advances in clinical research settings requires collaboration of quantitative and laboratory scientists. Biomarkers, new examples of which arise rapidly from new technologies, are used frequently in such areas as early detection of disease and identification of patients most likely to benefit from new therapies. There is also scientific interest in exploring whether, and under what conditions, biomarkers may substitute for clinical endpoints of phase III trials, although workshop participants agreed that these considerations apply primarily to situations where trials using clinical endpoints are not feasible. Evaluating candidate biomarkers in the exploratory phases of drug development and investigating surrogate endpoints in confirmatory trials require the establishment of a statistical and inferential framework. As a first step, participants reviewed methods for investigating the degree to which biomarkers can explain or predict the effect of treatments on clinical endpoints measured in clinical trials. They also suggested new approaches appropriate in settings where biomarkers reflect only indirectly the important processes on the causal path to clinical disease and where biomarker measurement errors are of concern. Participants emphasized the need for further research on development of such models, whether they are empirical in nature or attempt to describe mechanisms in mathematical terms. Of special interest were meta-analytic models for combining information from multiple studies involving interventions for the same condition. Recommendations also included considerations for design and conduct of trials and for assemblage of databases needed for such research. Finally, there was a strong recommendation for increased training of quantitative scientists in biologic research as well as in statistical methods and modeling to ensure that there will be an adequate workforce to meet future research needs.

(PDF emailed within 0-6 h: $19.90)

Accession: 010376768

Download citation: RISBibTeXText

PMID: 11578783

DOI: 10.1016/s0197-2456(01)00153-2


Related references

From The National Institutes of Health. Summary of the National Institutes of Health Research Workshop on the Epidemiology of the Acquired Immunodeficiency Syndrome (AIDS). Journal of Infectious Diseases 150(2): 295-303, 1984

National Institutes of Health workshop summary. Summary and recommendations of a workshop on the investigative use of fiberoptic bronchoscopy and bronchoalveolar lavage in individuals with asthma. Journal of Allergy and Clinical Immunology 76(2 Pt 1): 145-147, 1985

A unified framework for the evaluation of surrogate endpoints in mental-health clinical trials. Statistical Methods in Medical Research 19(3): 205-236, 2010

Developing Outcomes Assessments as Endpoints for Registrational Clinical Trials of Antibacterial Drugs: 2015 Update From the Biomarkers Consortium of the Foundation for the National Institutes of Health. Clinical Infectious Diseases 62(5): 603-607, 2016

Information-theory based surrogate marker evaluation from several randomized clinical trials with continuous true and binary surrogate endpoints. Clinical Trials 4(6): 587-597, 2007

From the National Institute of Allergy and Infectious Diseases of the National Institutes of Health, the Center for Disease Control, and the Bureau of Biologics of the Food and Drug Administration. Summary of clinical trials of influenza vaccines--II. Journal of Infectious Diseases 134(6): 633-638, 1976

From the National Institute of Allergy and Infectious Diseases. Summary of the National Institutes of Health workshop on group B streptococcal infection. Journal of Infectious Diseases 148(1): 163-166, 1983

Measuring hot flashes: summary of a National Institutes of Health workshop. Mayo Clinic Proceedings 79(6): 777-781, 2004

Summary of the National Institutes of Health Workshop on Group B Streptococcal Infection. Journal of Infectious Diseases 148(1): 163-166, 1983

Anhydramnios in the Setting of Renal Malformations: The National Institutes of Health Workshop Summary. Obstetrics and Gynecology 131(6): 1069-1079, 2018

From the National Institutes of Health. Summary of a workshop on cytomegalovirus infections during organ transplantation. Journal of Infectious Diseases 139(6): 728-734, 1979

Pigment gallstone disease: Summary of the National Institutes of Health--international workshop. Hepatology 2(6): 879-884, 1982

Screening and outcomes in biliary atresia: summary of a National Institutes of Health workshop. Hepatology 46(2): 566-581, 2007

DNA flow cytometry measurements as surrogate endpoints in chemoprevention trials: clinical, biological, and quality control considerations. Journal of Cellular Biochemistry. Supplement 17g: 212-218, 1993

Workshop on Chemoprevention of Breast Cancer Surrogate Endpoints and Agents in Short-Term Clinical Trials, Lake Tahoe, California, USA, October 6-10, 1993. Journal of Cellular Biochemistry Supplement 0(17G): 1-259, 1993