Design of the Women's Health Initiative clinical trial and observational study

G. Anderson, S. Cummings, L. S. Freedman, C. Furberg, M. Henderson, S. R. Johnson, L. Kuller, J. Manson, A. Oberman, R. L. Prentice, J. E. Rossouw., L. Finnegan, R. Hiatt, L. Pottern, J. McGowan, C. Clifford, B. Caan, V. Kipnis, B. Ettinger, S. SidneyG. Bailey, A. LaCroix, A. McTiernan, D. Bowen, C. Chen, B. Cochrane, J. Hunt, A. Kristal, B. Lund, R. Patterson, J. Probstfield, L. Tinker, N. Urban, C. Y. Wang, E. White, J. M. Kotchen, S. Shumaker, P. Rautaharju, F. Rautaharju, E. Stein, P. Laskarzewski, P. Steiner, K. Sagar, M. Nevitt, M. Dockrell, T. Fuerst, J. Himes, M. Stevens, F. Cammarata, S. Lindenfelser, B. Psaty, D. Siscovick, W. Longstreth, S. Heckbert, S. Wassertheil-Smoller, W. Frishman, Judith Wylie-Rosett, D. Barad, R. Freeman, S. Miller, J. Hays, R. Young, C. Crowley, M. A. DePoe, G. Burke, E. Paskett, L. Wagenknecht, R. Crouse, L. Parsons, T. Kotchen, E. Braunwald, J. Buring, C. Hennekens, J. M. Gaziano, A. R. Assaf, R. Carleton, M. Miller, C. Wheeler, A. Hume, M. Pedersen, O. Strickland, M. Huber, V. Porter, S. Beresford, V. Taylor, N. Woods, J. Hsia, V. Barnabei, M. Bovun, R. Chlebowski, R. Detrano, A. Nelson, J. Heiner, S. Pushkin, B. Valanis, V. Stevens, E. Whitlock, N. Karanja, A. Clark

Research output: Contribution to journalArticle

1658 Citations (Scopus)

Abstract

The Women's Health Initiative (WHI) is a large and complex clinical investigation of strategies for the prevention and control of some of the most common causes of morbidity and mortality among postmenopausal women, including cancer, cardiovascular disease, and osteoporotic fractures. The WHI was initiated in 1992, with a planned completion date of 2007. Postmenopausal women ranging in age from 50 to 79 are enrolled at one of 40 WHI clinical centers nationwide into either a clinical trial (CT) that will include about 64,500 women or an observational study (OS) that will include about 100,000 women. The CT is designed to allow randomized controlled evaluation of three distinct interventions: a low-fat eating pattern, hypothesized to prevent breast cancer and colorectal cancer and, secondarily, coronary heart disease; hormone replacement therapy, hypothesized to reduce the risk of coronary heart disease and other cardiovascular diseases and, secondarily, to reduce the risk of hip and other fractures, with increased breast cancer risk as a possible adverse outcome; and calcium and vitamin D supplementation, hypothesized to prevent hip fractures and, secondarily, other fractures and colorectal cancer. Overall benefit-versus-risk assessment is a central focus in each of the three CT components. Women are screened for participation in one or both of the components - dietary modification (DM) or hormone replacement therapy (HRT) - of the CT, which will randomize 48,000 and 27,500 women, respectively. Women who prove to be ineligible for, or who are unwilling to enroll in, these CT components are invited to enroll in the OS. At their 1-year anniversary of randomization, CT women are invited to be further randomized into the calcium and vitamin D (CaD) trial component, which is projected to include 45,000 women. The average follow-up for women in either CT or OS is approximately 9 years. Concerted efforts are made to enroll women of racial and ethnic minority groups, with a target of 20% of overall enrollment in both the CT and OS. This article gives a brief description of the rationale for the interventions being studied in each of the CT components and for the inclusion of the OS component. Some detail is provided on specific study design choices, including eligibility criteria, recruitment strategy, and sample size, with attention to the partial factorial design of the CT. Some aspects of the CT monitoring approach are also outlined. The scientific and logistic complexity of the WHI implies particular leadership and management challenges. The WHI organization and committee structure employed to respond to these challenges is also briefly described.

Original languageEnglish (US)
Pages (from-to)61-109
Number of pages49
JournalControlled Clinical Trials
Volume19
Issue number1
DOIs
StatePublished - Feb 1998
Externally publishedYes

Fingerprint

Women's Health
Observational Studies
Clinical Trials
Hormone Replacement Therapy
Hip Fractures
Vitamin D
Coronary Disease
Colorectal Neoplasms
Clinical Studies
Cardiovascular Diseases
Breast Neoplasms
Calcium
Diet Therapy
Minority Groups
Osteoporotic Fractures
Anniversaries and Special Events
Random Allocation
Ethnic Groups
Sample Size
Eating

Keywords

  • Calcium and vitamin D supplementation
  • Clinical trial monitoring
  • Cohort study
  • Dietary modification
  • Disease prevention
  • Hormone replacement therapy
  • Partial factorial design
  • Postmenopausal women
  • Randomized clinical trial
  • Study organization and management
  • Trial monitoring
  • Women's health

ASJC Scopus subject areas

  • Pharmacology

Cite this

Anderson, G., Cummings, S., Freedman, L. S., Furberg, C., Henderson, M., Johnson, S. R., ... Clark, A. (1998). Design of the Women's Health Initiative clinical trial and observational study. Controlled Clinical Trials, 19(1), 61-109. https://doi.org/10.1016/S0197-2456(97)00078-0

Design of the Women's Health Initiative clinical trial and observational study. / Anderson, G.; Cummings, S.; Freedman, L. S.; Furberg, C.; Henderson, M.; Johnson, S. R.; Kuller, L.; Manson, J.; Oberman, A.; Prentice, R. L.; Rossouw., J. E.; Finnegan, L.; Hiatt, R.; Pottern, L.; McGowan, J.; Clifford, C.; Caan, B.; Kipnis, V.; Ettinger, B.; Sidney, S.; Bailey, G.; LaCroix, A.; McTiernan, A.; Bowen, D.; Chen, C.; Cochrane, B.; Hunt, J.; Kristal, A.; Lund, B.; Patterson, R.; Probstfield, J.; Tinker, L.; Urban, N.; Wang, C. Y.; White, E.; Kotchen, J. M.; Shumaker, S.; Rautaharju, P.; Rautaharju, F.; Stein, E.; Laskarzewski, P.; Steiner, P.; Sagar, K.; Nevitt, M.; Dockrell, M.; Fuerst, T.; Himes, J.; Stevens, M.; Cammarata, F.; Lindenfelser, S.; Psaty, B.; Siscovick, D.; Longstreth, W.; Heckbert, S.; Wassertheil-Smoller, S.; Frishman, W.; Wylie-Rosett, Judith; Barad, D.; Freeman, R.; Miller, S.; Hays, J.; Young, R.; Crowley, C.; DePoe, M. A.; Burke, G.; Paskett, E.; Wagenknecht, L.; Crouse, R.; Parsons, L.; Kotchen, T.; Braunwald, E.; Buring, J.; Hennekens, C.; Gaziano, J. M.; Assaf, A. R.; Carleton, R.; Miller, M.; Wheeler, C.; Hume, A.; Pedersen, M.; Strickland, O.; Huber, M.; Porter, V.; Beresford, S.; Taylor, V.; Woods, N.; Hsia, J.; Barnabei, V.; Bovun, M.; Chlebowski, R.; Detrano, R.; Nelson, A.; Heiner, J.; Pushkin, S.; Valanis, B.; Stevens, V.; Whitlock, E.; Karanja, N.; Clark, A.

In: Controlled Clinical Trials, Vol. 19, No. 1, 02.1998, p. 61-109.

Research output: Contribution to journalArticle

Anderson, G, Cummings, S, Freedman, LS, Furberg, C, Henderson, M, Johnson, SR, Kuller, L, Manson, J, Oberman, A, Prentice, RL, Rossouw., JE, Finnegan, L, Hiatt, R, Pottern, L, McGowan, J, Clifford, C, Caan, B, Kipnis, V, Ettinger, B, Sidney, S, Bailey, G, LaCroix, A, McTiernan, A, Bowen, D, Chen, C, Cochrane, B, Hunt, J, Kristal, A, Lund, B, Patterson, R, Probstfield, J, Tinker, L, Urban, N, Wang, CY, White, E, Kotchen, JM, Shumaker, S, Rautaharju, P, Rautaharju, F, Stein, E, Laskarzewski, P, Steiner, P, Sagar, K, Nevitt, M, Dockrell, M, Fuerst, T, Himes, J, Stevens, M, Cammarata, F, Lindenfelser, S, Psaty, B, Siscovick, D, Longstreth, W, Heckbert, S, Wassertheil-Smoller, S, Frishman, W, Wylie-Rosett, J, Barad, D, Freeman, R, Miller, S, Hays, J, Young, R, Crowley, C, DePoe, MA, Burke, G, Paskett, E, Wagenknecht, L, Crouse, R, Parsons, L, Kotchen, T, Braunwald, E, Buring, J, Hennekens, C, Gaziano, JM, Assaf, AR, Carleton, R, Miller, M, Wheeler, C, Hume, A, Pedersen, M, Strickland, O, Huber, M, Porter, V, Beresford, S, Taylor, V, Woods, N, Hsia, J, Barnabei, V, Bovun, M, Chlebowski, R, Detrano, R, Nelson, A, Heiner, J, Pushkin, S, Valanis, B, Stevens, V, Whitlock, E, Karanja, N & Clark, A 1998, 'Design of the Women's Health Initiative clinical trial and observational study', Controlled Clinical Trials, vol. 19, no. 1, pp. 61-109. https://doi.org/10.1016/S0197-2456(97)00078-0
Anderson G, Cummings S, Freedman LS, Furberg C, Henderson M, Johnson SR et al. Design of the Women's Health Initiative clinical trial and observational study. Controlled Clinical Trials. 1998 Feb;19(1):61-109. https://doi.org/10.1016/S0197-2456(97)00078-0
Anderson, G. ; Cummings, S. ; Freedman, L. S. ; Furberg, C. ; Henderson, M. ; Johnson, S. R. ; Kuller, L. ; Manson, J. ; Oberman, A. ; Prentice, R. L. ; Rossouw., J. E. ; Finnegan, L. ; Hiatt, R. ; Pottern, L. ; McGowan, J. ; Clifford, C. ; Caan, B. ; Kipnis, V. ; Ettinger, B. ; Sidney, S. ; Bailey, G. ; LaCroix, A. ; McTiernan, A. ; Bowen, D. ; Chen, C. ; Cochrane, B. ; Hunt, J. ; Kristal, A. ; Lund, B. ; Patterson, R. ; Probstfield, J. ; Tinker, L. ; Urban, N. ; Wang, C. Y. ; White, E. ; Kotchen, J. M. ; Shumaker, S. ; Rautaharju, P. ; Rautaharju, F. ; Stein, E. ; Laskarzewski, P. ; Steiner, P. ; Sagar, K. ; Nevitt, M. ; Dockrell, M. ; Fuerst, T. ; Himes, J. ; Stevens, M. ; Cammarata, F. ; Lindenfelser, S. ; Psaty, B. ; Siscovick, D. ; Longstreth, W. ; Heckbert, S. ; Wassertheil-Smoller, S. ; Frishman, W. ; Wylie-Rosett, Judith ; Barad, D. ; Freeman, R. ; Miller, S. ; Hays, J. ; Young, R. ; Crowley, C. ; DePoe, M. A. ; Burke, G. ; Paskett, E. ; Wagenknecht, L. ; Crouse, R. ; Parsons, L. ; Kotchen, T. ; Braunwald, E. ; Buring, J. ; Hennekens, C. ; Gaziano, J. M. ; Assaf, A. R. ; Carleton, R. ; Miller, M. ; Wheeler, C. ; Hume, A. ; Pedersen, M. ; Strickland, O. ; Huber, M. ; Porter, V. ; Beresford, S. ; Taylor, V. ; Woods, N. ; Hsia, J. ; Barnabei, V. ; Bovun, M. ; Chlebowski, R. ; Detrano, R. ; Nelson, A. ; Heiner, J. ; Pushkin, S. ; Valanis, B. ; Stevens, V. ; Whitlock, E. ; Karanja, N. ; Clark, A. / Design of the Women's Health Initiative clinical trial and observational study. In: Controlled Clinical Trials. 1998 ; Vol. 19, No. 1. pp. 61-109.
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TY - JOUR

T1 - Design of the Women's Health Initiative clinical trial and observational study

AU - Anderson, G.

AU - Cummings, S.

AU - Freedman, L. S.

AU - Furberg, C.

AU - Henderson, M.

AU - Johnson, S. R.

AU - Kuller, L.

AU - Manson, J.

AU - Oberman, A.

AU - Prentice, R. L.

AU - Rossouw., J. E.

AU - Finnegan, L.

AU - Hiatt, R.

AU - Pottern, L.

AU - McGowan, J.

AU - Clifford, C.

AU - Caan, B.

AU - Kipnis, V.

AU - Ettinger, B.

AU - Sidney, S.

AU - Bailey, G.

AU - LaCroix, A.

AU - McTiernan, A.

AU - Bowen, D.

AU - Chen, C.

AU - Cochrane, B.

AU - Hunt, J.

AU - Kristal, A.

AU - Lund, B.

AU - Patterson, R.

AU - Probstfield, J.

AU - Tinker, L.

AU - Urban, N.

AU - Wang, C. Y.

AU - White, E.

AU - Kotchen, J. M.

AU - Shumaker, S.

AU - Rautaharju, P.

AU - Rautaharju, F.

AU - Stein, E.

AU - Laskarzewski, P.

AU - Steiner, P.

AU - Sagar, K.

AU - Nevitt, M.

AU - Dockrell, M.

AU - Fuerst, T.

AU - Himes, J.

AU - Stevens, M.

AU - Cammarata, F.

AU - Lindenfelser, S.

AU - Psaty, B.

AU - Siscovick, D.

AU - Longstreth, W.

AU - Heckbert, S.

AU - Wassertheil-Smoller, S.

AU - Frishman, W.

AU - Wylie-Rosett, Judith

AU - Barad, D.

AU - Freeman, R.

AU - Miller, S.

AU - Hays, J.

AU - Young, R.

AU - Crowley, C.

AU - DePoe, M. A.

AU - Burke, G.

AU - Paskett, E.

AU - Wagenknecht, L.

AU - Crouse, R.

AU - Parsons, L.

AU - Kotchen, T.

AU - Braunwald, E.

AU - Buring, J.

AU - Hennekens, C.

AU - Gaziano, J. M.

AU - Assaf, A. R.

AU - Carleton, R.

AU - Miller, M.

AU - Wheeler, C.

AU - Hume, A.

AU - Pedersen, M.

AU - Strickland, O.

AU - Huber, M.

AU - Porter, V.

AU - Beresford, S.

AU - Taylor, V.

AU - Woods, N.

AU - Hsia, J.

AU - Barnabei, V.

AU - Bovun, M.

AU - Chlebowski, R.

AU - Detrano, R.

AU - Nelson, A.

AU - Heiner, J.

AU - Pushkin, S.

AU - Valanis, B.

AU - Stevens, V.

AU - Whitlock, E.

AU - Karanja, N.

AU - Clark, A.

PY - 1998/2

Y1 - 1998/2

N2 - The Women's Health Initiative (WHI) is a large and complex clinical investigation of strategies for the prevention and control of some of the most common causes of morbidity and mortality among postmenopausal women, including cancer, cardiovascular disease, and osteoporotic fractures. The WHI was initiated in 1992, with a planned completion date of 2007. Postmenopausal women ranging in age from 50 to 79 are enrolled at one of 40 WHI clinical centers nationwide into either a clinical trial (CT) that will include about 64,500 women or an observational study (OS) that will include about 100,000 women. The CT is designed to allow randomized controlled evaluation of three distinct interventions: a low-fat eating pattern, hypothesized to prevent breast cancer and colorectal cancer and, secondarily, coronary heart disease; hormone replacement therapy, hypothesized to reduce the risk of coronary heart disease and other cardiovascular diseases and, secondarily, to reduce the risk of hip and other fractures, with increased breast cancer risk as a possible adverse outcome; and calcium and vitamin D supplementation, hypothesized to prevent hip fractures and, secondarily, other fractures and colorectal cancer. Overall benefit-versus-risk assessment is a central focus in each of the three CT components. Women are screened for participation in one or both of the components - dietary modification (DM) or hormone replacement therapy (HRT) - of the CT, which will randomize 48,000 and 27,500 women, respectively. Women who prove to be ineligible for, or who are unwilling to enroll in, these CT components are invited to enroll in the OS. At their 1-year anniversary of randomization, CT women are invited to be further randomized into the calcium and vitamin D (CaD) trial component, which is projected to include 45,000 women. The average follow-up for women in either CT or OS is approximately 9 years. Concerted efforts are made to enroll women of racial and ethnic minority groups, with a target of 20% of overall enrollment in both the CT and OS. This article gives a brief description of the rationale for the interventions being studied in each of the CT components and for the inclusion of the OS component. Some detail is provided on specific study design choices, including eligibility criteria, recruitment strategy, and sample size, with attention to the partial factorial design of the CT. Some aspects of the CT monitoring approach are also outlined. The scientific and logistic complexity of the WHI implies particular leadership and management challenges. The WHI organization and committee structure employed to respond to these challenges is also briefly described.

AB - The Women's Health Initiative (WHI) is a large and complex clinical investigation of strategies for the prevention and control of some of the most common causes of morbidity and mortality among postmenopausal women, including cancer, cardiovascular disease, and osteoporotic fractures. The WHI was initiated in 1992, with a planned completion date of 2007. Postmenopausal women ranging in age from 50 to 79 are enrolled at one of 40 WHI clinical centers nationwide into either a clinical trial (CT) that will include about 64,500 women or an observational study (OS) that will include about 100,000 women. The CT is designed to allow randomized controlled evaluation of three distinct interventions: a low-fat eating pattern, hypothesized to prevent breast cancer and colorectal cancer and, secondarily, coronary heart disease; hormone replacement therapy, hypothesized to reduce the risk of coronary heart disease and other cardiovascular diseases and, secondarily, to reduce the risk of hip and other fractures, with increased breast cancer risk as a possible adverse outcome; and calcium and vitamin D supplementation, hypothesized to prevent hip fractures and, secondarily, other fractures and colorectal cancer. Overall benefit-versus-risk assessment is a central focus in each of the three CT components. Women are screened for participation in one or both of the components - dietary modification (DM) or hormone replacement therapy (HRT) - of the CT, which will randomize 48,000 and 27,500 women, respectively. Women who prove to be ineligible for, or who are unwilling to enroll in, these CT components are invited to enroll in the OS. At their 1-year anniversary of randomization, CT women are invited to be further randomized into the calcium and vitamin D (CaD) trial component, which is projected to include 45,000 women. The average follow-up for women in either CT or OS is approximately 9 years. Concerted efforts are made to enroll women of racial and ethnic minority groups, with a target of 20% of overall enrollment in both the CT and OS. This article gives a brief description of the rationale for the interventions being studied in each of the CT components and for the inclusion of the OS component. Some detail is provided on specific study design choices, including eligibility criteria, recruitment strategy, and sample size, with attention to the partial factorial design of the CT. Some aspects of the CT monitoring approach are also outlined. The scientific and logistic complexity of the WHI implies particular leadership and management challenges. The WHI organization and committee structure employed to respond to these challenges is also briefly described.

KW - Calcium and vitamin D supplementation

KW - Clinical trial monitoring

KW - Cohort study

KW - Dietary modification

KW - Disease prevention

KW - Hormone replacement therapy

KW - Partial factorial design

KW - Postmenopausal women

KW - Randomized clinical trial

KW - Study organization and management

KW - Trial monitoring

KW - Women's health

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DO - 10.1016/S0197-2456(97)00078-0

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