|FOTI, KATHRYN - Johns Hopkins University|
|FORAKER, RANDI - Washington University|
|MARTYN-NEMETH, PAMELA - University Of Illinois|
|ANDERSON, CHERYL - University Of California|
|COOK, NANCY - Brigham & Women'S Hospital|
|LICHTENSTEIN, ALICE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|DE FERRANTI, SARAH - Boston Children'S Hospital|
|ROHM YOUNG, DEBORAH - Kaiser Permanente|
|HIVERT, MARIE-FRANCE - Harvard Pilgrim Health Care Institute|
|ROSS, ROBERT - Queen'S University - Canada|
|DEEDWANIA, PRAKASH - University Of California|
|WHITSEL, LAURIE - American Heart Association|
|APPEL, LAWRENCE - Johns Hopkins University|
Submitted to: Circulation: Cardiovascular Quality and Outcomes
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/28/2020
Publication Date: 9/28/2020
Citation: Foti, K., Foraker, R.E., Martyn-Nemeth, P., Anderson, C.A., Cook, N.R., Lichtenstein, A.H., De Ferranti, S.D., Rohm Young, D., Hivert, M., Ross, R., Deedwania, P., Whitsel, L.P., Appel, L.J. 2020. Evidence-based policy making for public health interventions in cardiovascular diseases: formally assessing the feasibility of clinical trials. Circulation: Cardiovascular Quality and Outcomes. 13:e006378. https://doi.org/10.1161/CIRCOUTCOMES.119.006378.
Interpretive Summary: Development of public health risk reduction policies is often delayed by lack of evidence from randomized controlled trials that establish cause and effect. Randomized controlled trials are lacking in some areas due to logistical and ethical considerations for conducting such studies (e.g., cost, timing, fairness to study subjects). In this situation what is needed is clear guidance for how to use the available evidence to establish prevention policy recommendations. To address this issue a case study was conducted. We designed and assessed the feasibility of conducting a randomized controlled trial of sodium reduction on cardiovascular outcomes. A trial using any of the designs considered would require tens of thousands of participants and cost hundreds of millions of dollars, hence, would likely be prohibitive to conduct. On the basis of these results we suggest a framework should be developed to guide the scientific community when challenged with establishing evidence-based public health prevention policies, including dietary recommendations, in situations where we do not have randomized controlled trial data.
Technical Abstract: Implementation of prevention policies has often been impeded or delayed due to the lack of randomized controlled trials (RCTs) with 'hard' clinical outcomes (e.g., incident disease, mortality). Despite the prominent role of RCTs in health care, it may not always be feasible to conduct RCTs of public health interventions with hard outcomes due to logistical and ethical considerations. RCTs may also lack external validity and have limited generalizability. Currently, there is insufficient guidance for policymakers charged with establishing evidence-based policy to determine whether an RCT with hard outcomes is needed prior to policy recommendations. In this context, the purpose of this paper is to assess, in a case study, the feasibility of conducting an RCT of the oft-cited issue of sodium reduction on cardiovascular outcomes, and then propose a framework for decision-making, which includes an assessment of the feasibility of conducting an RCT with hard clinical outcomes when such trials are unavailable. We designed and assessed the feasibility of potential individual- and cluster-randomized trials of sodium reduction on cardiovascular outcomes. Based on our assumptions, a trial using any of the designs considered would require tens of thousands of participants and cost hundreds of millions of dollars, which is prohibitively expensive. Our estimates may be conservative given several key challenges, such as the unknown costs of sustaining a long-term difference in sodium intake, the effect of differential co-treatment with anti-hypertensive medications, and long lag-time to clinical outcomes. Thus, it would be extraordinarily difficult to conduct such a trial, and despite the high costs, there would be a substantial risk for a spuriously null result. A robust framework, such as the one we developed, should be used to guide policymakers when establishing evidence-based public health interventions in the absence of trials with hard clinical outcomes.