The promise and peril of surrogate end points in cancer research

Nature Reviews Cancer

Volumn 2, Issue 1, 2002, Pages 19-27

  Schatzkin, Arthur ^a   Gail, Mitchell ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

TUMOR MARKER; BIOLOGICAL MARKER; GROWTH PROMOTOR; HORMONE; TUMOR ANTIGEN;

CANCER; CANCER EPIDEMIOLOGY; CANCER INCIDENCE; CANCER MORTALITY; CANCER PREVENTION; CANCER RECURRENCE; CANCER RESEARCH; CANCER RISK; CARCINOGENESIS; COLORECTAL CANCER; DISEASE MARKER; HUMAN; PRIORITY JOURNAL; PROGNOSIS; PROSPECTIVE STUDY; RELIABILITY; REVIEW; UTERINE CERVIX CANCER; VALIDATION PROCESS; ADENOMA; ADENOMATOUS POLYP; BIOLOGICAL MODEL; CLINICAL TRIAL; COLON POLYP; COLORECTAL TUMOR; ENVIRONMENTAL EXPOSURE; EPITHELIUM; FEMALE; HYPERPLASIA; INCIDENCE; INFECTION; INTERVENTION STUDY; MALE; METABOLISM; METHODOLOGY; NEOPLASM; OUTCOME ASSESSMENT; PAPILLOMA VIRUS; PATHOLOGY; STANDARD; STATISTICS; SURVIVAL; TUMOR RECURRENCE; UTERINE CERVIX TUMOR; VIROLOGY; VIRUS INFECTION;

ADENOMA; ADENOMATOUS POLYPS; ANTIGENS, NEOPLASM; BIOLOGICAL MARKERS; CLINICAL TRIALS; COLONIC POLYPS; COLORECTAL NEOPLASMS; ENVIRONMENTAL EXPOSURE; EPITHELIUM; FEMALE; GROWTH SUBSTANCES; HORMONES; HUMANS; HYPERPLASIA; INCIDENCE; INFECTION; INTERVENTION STUDIES; MALE; MODELS, BIOLOGICAL; NEOPLASM RECURRENCE, LOCAL; NEOPLASMS; OUTCOME ASSESSMENT (HEALTH CARE); PAPILLOMAVIRIDAE; PAPILLOMAVIRUS INFECTIONS; SURVIVAL ANALYSIS; UTERINE CERVICAL NEOPLASMS;

EID: 0036372284     PISSN: 1474175X     EISSN: None     Source Type: Journal    
DOI: 10.1038/nrc702     Document Type: Review

References (55)

1. Women's Health Initiative Study Group. Design of the Women's Health Initiative Clinical Trial and Observational Study, Control Clin. Trials 19, 61-109 (1998).
2. DeGruttola, V. G. et al. Considerations in the evaluation of surrogate endpoints in clinical trials: summary of a National Institutes of Health workshop. Control. Clin. Trials (in the press). Reviews useful surrogates and Phase III clinical trials, in which their use is often problematic. Sets out statistical concepts and approaches to evaluating surrogate markers, and an agenda for research and resources needed to promote the proper use of surrogates.
3. New drug, antibiotic and biological drug product regulations: accelerated approval. Proposed Rule. 57 Federal Register 13234-13232, 1992.
4. Prentice, R. L. Surrogate endpoints in clinical trials: definition and operational criteria. Stat. Med. 8, 431-440 (1989). Defines criteria for the validity of a surrogate marker for testing the hypothesis of no association between a treatment and a true clinical outcome.
5. Daniels. M. J. & Hughes, M. D. Meta-analysis for the evaluation of potential surrogate markers. Stat. Med. 16, 1965-1982 (1997).
6. Buyse, M., Molenberghs, G., Burzykowski, T., Renard, D. & Geys, H. The validation of surrogate endpoints in meta-analyses of randomized experiments. Biostatistics 1, 49-67 (2000). Defines the concept of trial-level validity of a surrogate, based on meta-analysis of a set of trials. Illustrates the use of meta-analytical data for predicting the size of the effect of a new treatment on the true clinical outcome from data on its effect on the surrogate outcome.
7. Gail, M. H., Pfeiffer, R., Houwelingen, H. C. W. & Carroll, R. J. On meta-analytic assessment of surrogate outcomes Biostatistics 1, 231-246 (2000).
8. Temple, R. Are surrogate markers adequate to assess cardiovascular disease drugs? J. Am. Med. Assoc. 282, 790-795 (1999).
9. Wargovich, M. J. in Prevention and Early Detection of Colorectal Cancer (eds Young, G. P., Rozen, P. & Levin, B) 89-101 (London, W. B. Saunders Co. Ltd, 1996).
10. Rothman, K. J. & Greenland, S. Modem Epidemiology (Philadelphia, Lippincott-Raven, 1998).
11. 3H]thymidine labeling patterns in colonic epithelial cells. Cancer Res. 44, 4201-4207 (1984).
12. Toniolo, P. G. et al. A prospective study of endogenous estrogens and breast cancer in postmenopausal women. J. Natl. Cancer Inst. 87, 190-197 (1995).
13. Hankinson, S. E. et al. Plasma sex steroid hormone levels and risk of breast cancer in postmenopausal women. J. Natl Cancer Inst. 90. 1292-1299 (1998).
14. Schiffman, M. H. et al. Epidemiologic evidence showing that human papillomavirus infection causes most cervical intraepithelial neoplasia. J. Natl. Cancer Inst. 85, 958-964 (1993).
15. Schatzkin, A. et al. Lack of effect of a low-fat, high-fiber, diet on the recurrence of colorectal adenomas. N. Engl. J. Med. 342, 1149-1155 (2000).
16. Holt, P. R. et al. Modulation of abnormal colonic epithelial cell proliferation and differentiation by low-fat dairy foods: a randomized controlled trial. J. Am. Med. Assoc. 280, 1074-1079 (1998).
17. Prentice, R. et al. Dietary fat reduction and plasma estradiol concentration in healthy premenopausal women. J. Natl Cancer Inst. 82, 129-134 (1990).
18. Reichman, M. E. et al. Effects of moderate alcohol consumption on plasma and unnary hormone concentrations in premenopausal women. J. Natl Cancer Inst. 85, 722-727 (1993).
19. Baron, J. A. et al. Calcium supplementation and rectal mucosal proliferation: a randomized controlled trial. J. Natl Cancer Inst. 87, 1303-1307 (1995).
20. Baron, J. A. et al. Calcium supplements for the prevention of colorectal adenomas. N. Engl. J. Med. 340, 101-107 (1999).
21. Schiffman, M. H. et al. Epidemiologic evidence showing that human papillomavirus infection causes most cervical intraepithelial neoplasia. J. Natl Cancer Inst. 85, 958-964 (1993).
22. Freedman, L. S, Graubard, B. I. & Schatzkin, A. Statistical validation of intermediate endpoints for chronic diseases, Stat. Med. 11, 167-178 (1992).
23. Buyse, M. & Molenberghs, G. Criteria for the validation of surrogate endpoints in randomized experiments. Biometrics 54, 1014-1029 (1998).
24. DeGruttola. V., Fleming, T., Lin,. D. Y. & Coombs, R. Perpsective: validating surrogate markers - are we being naive? J. Infect. Dis. 175, 237-246 (1997).
25. Schiffman, M. H. & Schatzkin, A. Test reliability is critically important to molecular epidemiology: an example from studies of human papillomavirus infection and cervical neoplasia. Cancer Res. 54, S1944-S1947 (1994).
26. Franco, E. L. The sexually transmitted disease model for cervical cancer: incoherent epidemiologic findings and the role of misclassification of human papillomavirus infection. Epidemiology 2, 98-106 (1991).
27. zur Hausen, H. Papillomaviruses causing cancer: evasion from host-cell control in early events in carcinogenesis. J. Natl Cancer Inst. 92, 690-698 (2000).
28. Sugarbaker, P. H., Gunderson, L. L. & Wittes, R. E. in Cancer: Principles and Practice Oncology (eds DeVita, V. T. Jr, Hellman, S. & Rosenberg, S. A.) 795-884 (J. B. Lippincott Co., Philadelphia, 1985).
29. Paraskeva, C. et al. Colorectal carcinogenesis: sequential steps in the vitro immortalization and transformation of human colonic epithelial cells. Anticancer Res. 10, 1189-1200 (1990).
30. Fearon, E. R. & Vogelstein, B. A genetic model for colorectal tumorigenesis. Cell 61, 759-767 (1990).
31. Fleiss, J. L. The Design and Analysis of Clinical Experiments 1-5 (New York, John Wiley & Sons, 1986).
32. Hankinson, S. E. et al. Reproducibility of plasma hormone levels in postmenopausal women over a 2-3-year period. Cancer Epidemiol. Biomarker Prev. 4, 649-654 (1995).
33. Lyles, C. M. et al. Reproducibility and variability of the rectal mucosal proliferation index using proliferating cell nuclear antigen immunohistochemistry. Cancer Epidemiol. Biomarker Prev. 3, 597-605 (1994).
34. Fleming, T. R. & DeMets, D. L. Surrogate end points in clinical trials: are we being misled? Ann. Intern. Med 125, 605-613 (1996). Presents several examples from clinical studies of surrogate end point findings that did not agree with true end-point results.
35. Mitchell, M. F. Hittelman, W. N. Hong, W. K., Lotan, R. & Schottenfeld, D. The natural history of cervical intraepithelial neoplasia: an argument for intermediate endpoint biomarkers. Cancer Epidemiol. Biomarker Prev. 3, 619-626 (1994).
36. Bostwick, D. G. Prostatic intraepithelial neoplasia is a risk factor for cancer. Semin. Urol. Oncol. 17, 187-198 (1999).
37. Mutter, G. L. Endometrial intraepithelial neoplasia (EIN): will it bring order to chaos? Gynecol. Oncol. 76, 287-290 (2000).
38. Schatzkin, A., Freedman, L. S., Dawsey, S. M. & Lanza, E. Interpreting precursor studies: what polyp trials tell us about large bowel cancer. J. Natl Cancer Inst. 86, 1053-1057 (1994).
39. Misset, J. L. et al. Regression of bronchial epidermoid metaplasia in heavy smokers with etretinate treatment Cancer Detect. Prev. 9, 167-170 (1986).
40. Dawsey, S. M. et al. Mucosal iodine staining improves endoscopic visualization of squamous dysplasia and squamous cell carcinoma of the esophagus in Linxian, China. Cancer 83, 220-231 (1998).
41. Saftlas, A. F. et al. Mammographic parenchymal patterns as indicators of breast cancer risk. Am. J. Epidemiol. 129, 518-526 (1989).
42. Karlan, B. Y. Screening for ovarian cancer: what are the optimal surrogate endpoints for clinical trials? J. Cell Biochem. 23 (Suppl.), 227-232 (1995).
43. Baron, J. A. et al. Epidemiological use of rectal proliferation measures. Cancer Epidemiol. Biomarker Prev. 4, 57-61 (1995).
44. Bedi, A. et al. Inhibition of apoptosis during development of colorectal cancer. Cancer Res. 55, 1811-1816 (1995).
45. Tsiatis, A. A. DeGruttola, V. & Wulfsohn, M. S. Modeling the relationship of survival to longitudinal data measured with error. Applications to survival and CD4 counts in patients with AIDS. J. Am. Stat. Assoc. 90, 27-37 (1995).
46. Ruiz, L. et al. Plasma HIV-1 RNA as a predictor of the efficacy of adding zalcitabine to a previous regimen with zidovudine. Antivir. Ther. 1, 220-224 (1996).
47. Fearon, E. R. Genetic alterations underlying colorectal tumorigenesis. Cancer Surveys 12, 119-136 (1992).
48. Counts, J. L. & Goodman, J. I. Alterations in DNA methylation may play a variety of roles in carcinogenesis. Cell 83, 13-15 (1995).
49. Brown, P. O. & Botstein, D. Exploring the new world of the genome with DNA microarrays. Nature Genet. 21, S33-S37 (1999).
50. Groopman, J. D., Wogan, G. N., Roebuck B. D. & Kensler, T. W. Molecular biomarkers for aflatoxins and their application to human cancer prevention. Cancer Res. 54, S1907-S1911 (1994).
51. Schiffman, M. H. Recent progress in defining the epidemiology of human papillomavirus infection and cervical neoplasia. J. Natl Cancer Inst. 84, 394-398 (1992).
52. Munoz, N. is Helicobacter pylori a cause of gastric cancer? An appraisal of the seroepidemiological evidence. Cancer Epidemiol. Biomarker Prev. 3, 445-451 (1994).
53. Blattner, W. A. in Viral Infections in Humans 3rd edn (ed. Evans, A. S) 545-592 (Plenum Medical Book Co., New York, 1989).
54. Balkwill, F. & Mantovani. A Inflammation and cancer: back to Virchow? Lancet 539-539 (2001).
55. Dorgan, J. E. et al. Relations of prediagnostic serum estrogen and androgen levels to breast cancer risk. Cancer Epidemiol. Biomarker Prev. 5, 533-539 (1996).