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Recruitment of women to clinical trials
EDITORIAL
THE LANCET Volume 358, Number 9285
Recruitment of women to clinical trials Researchers are having difficulty in recruiting women to breast-cancer trials. Even women at high risk of developing breast cancer are not taking part in randomised controlled trials. As reported in a Research Letter this week (p 889), for the past 8 years in a region of the UK women who have a greater than 40% lifetime risk of breast cancer have been offered entry into two chemoprevention trials, or a study of risk-reducing mastectomy, or a study of breast screening by magnetic resonance imaging. Women not wishing to take part in any of the four studies are offered annual mammography. Only 10% of eligible women have entered each chemoprevention trial and another 10% have chosen the mastectomy study, whereas 60% have opted for the screening study. The uptake is so low for the chemoprevention or mastectomy studies that they may not enable conclusions on efficacy. Why do these women at high risk of breast cancer not wish to participate in trials offering intervention (drugs or surgery)? Admittedly the options being offered differ widely, but such at-risk women, and their daughters, have after all much to gain from establishing which preventive strategy is most effective. The two explanations offered by the researchers—the reluctance of women to accept the random allocation of placebo in one chemoprevention study or the probability of hormonal symptoms with the active arm of the other study—are likely, but could there be other factors? Could women be influenced by how they are asked? To persuade women to accept an equal chance of receiving placebo, the evidence that no available preventive strategy works has to be strong and to be properly presented. Who presents that information may also be influential. Could women, especially those at risk from, or with, diseases that affect mainly women, be more likely to take part if approached by women? Since women are more likely to be sympathetic to practical issues such as the number of breast examinations required, their involvement at all stages of trial design and recruitment might improve the likelihood of adequately powered trials being completed. THE LANCET • Vol 358 • September 15, 2001
But difficulties in recruiting female patients extend far beyond breast-cancer trials. In the USA, the National Institutes of Health (NIH) Revitalization Act of 1993 was the result of evidence that women’s health isssues were not being addressed by clinical trials. That Act required that women and minority groups be included in clinical research so that differences in intervention effects could be analysed. However, a study report in JAMA last month showed that, relative to disease prevalence, women remained under-represented in published randomised controlled trials of acute coronary syndromes. The authors of that study conclude that recruitment biases are undermining efforts to provide evidence-based care to cardiac patients. In 2000, NIH guidelines were revised to state that if an intervention was expected to produce differences of clinical or public-health importance among subgroups (such as men or women), the study must be designed to measure these differences as primary outcomes. A difficulty is that often differences in effect are suspected only on completion of the study. For example, ASSENT-3 reported in The Lancet (Aug 25, p 605) shows that patients with acute myocardial infarction given tenecteplase with enoxaparin or abciximab do better than those treated with tenecteplase plus unfractionated heparin. However, as discussed at the European Society of Cardiology meeting in Stockholm last week, for women there is no difference between the treatment arms once the risk of bleeding is taken into account. Why there is a difference between men and women once the safety endpoint is included is unclear. Clarifying the reason for such differences through studies into underlying biological mechanisms would help in the development of appropriate recruitment strategies, and possibly of trial design and therapy. Meanwhile, to ensure that women benefit fully from research being done, all effort should be made to recruit them in adequate numbers into any study of disorders affecting women. The Lancet 853
THE LANCET Volume 358, Number 9285
Recruitment of women to clinical trials Researchers are having difficulty in recruiting women to breast-cancer trials. Even women at high risk of developing breast cancer are not taking part in randomised controlled trials. As reported in a Research Letter this week (p 889), for the past 8 years in a region of the UK women who have a greater than 40% lifetime risk of breast cancer have been offered entry into two chemoprevention trials, or a study of risk-reducing mastectomy, or a study of breast screening by magnetic resonance imaging. Women not wishing to take part in any of the four studies are offered annual mammography. Only 10% of eligible women have entered each chemoprevention trial and another 10% have chosen the mastectomy study, whereas 60% have opted for the screening study. The uptake is so low for the chemoprevention or mastectomy studies that they may not enable conclusions on efficacy. Why do these women at high risk of breast cancer not wish to participate in trials offering intervention (drugs or surgery)? Admittedly the options being offered differ widely, but such at-risk women, and their daughters, have after all much to gain from establishing which preventive strategy is most effective. The two explanations offered by the researchers—the reluctance of women to accept the random allocation of placebo in one chemoprevention study or the probability of hormonal symptoms with the active arm of the other study—are likely, but could there be other factors? Could women be influenced by how they are asked? To persuade women to accept an equal chance of receiving placebo, the evidence that no available preventive strategy works has to be strong and to be properly presented. Who presents that information may also be influential. Could women, especially those at risk from, or with, diseases that affect mainly women, be more likely to take part if approached by women? Since women are more likely to be sympathetic to practical issues such as the number of breast examinations required, their involvement at all stages of trial design and recruitment might improve the likelihood of adequately powered trials being completed. THE LANCET • Vol 358 • September 15, 2001
But difficulties in recruiting female patients extend far beyond breast-cancer trials. In the USA, the National Institutes of Health (NIH) Revitalization Act of 1993 was the result of evidence that women’s health isssues were not being addressed by clinical trials. That Act required that women and minority groups be included in clinical research so that differences in intervention effects could be analysed. However, a study report in JAMA last month showed that, relative to disease prevalence, women remained under-represented in published randomised controlled trials of acute coronary syndromes. The authors of that study conclude that recruitment biases are undermining efforts to provide evidence-based care to cardiac patients. In 2000, NIH guidelines were revised to state that if an intervention was expected to produce differences of clinical or public-health importance among subgroups (such as men or women), the study must be designed to measure these differences as primary outcomes. A difficulty is that often differences in effect are suspected only on completion of the study. For example, ASSENT-3 reported in The Lancet (Aug 25, p 605) shows that patients with acute myocardial infarction given tenecteplase with enoxaparin or abciximab do better than those treated with tenecteplase plus unfractionated heparin. However, as discussed at the European Society of Cardiology meeting in Stockholm last week, for women there is no difference between the treatment arms once the risk of bleeding is taken into account. Why there is a difference between men and women once the safety endpoint is included is unclear. Clarifying the reason for such differences through studies into underlying biological mechanisms would help in the development of appropriate recruitment strategies, and possibly of trial design and therapy. Meanwhile, to ensure that women benefit fully from research being done, all effort should be made to recruit them in adequate numbers into any study of disorders affecting women. The Lancet 853