Supporting Impactful Clinical Trials of Complementary and Integrative Health Approaches

Introduction and Explanation of Need

To achieve the NCCIH mission to determine, through rigorous scientific investigation, the fundamental science, usefulness, and safety of complementary and integrative health approaches and their roles in improving health and health care, NCCIH supports clinical trials to assess the safety, efficacy, and effectiveness of these approaches. NCCIH defines impactful clinical trials as those that 1) provide evidence to inform clinical practice guidelines and health care policies or 2) provide sufficient preliminary data to inform the design of and ability to conduct fully powered clinical trials. Fully powered trials must be rigorously performed using randomized controlled designs with adequate study power to test the primary hypothesis. To enhance generalizability and meet NIH policy requirements, it is important that fully powered trials recruit participants from different geographic regions and include a diverse sample of participants that reflects the U.S. patient population with the condition being studied.

NCCIH has developed a framework for human subjects research that describes the range of research supported from basic and mechanistic studies through dissemination and implementation science studies. Within the framework, NCCIH prioritizes the need for preliminary feasibility and acceptability data from the literature or a feasibility study to have confidence that a fully powered efficacy or effectiveness study can be conducted. For this priority area, NCCIH is emphasizing the support of clinical trials that will inform clinical guidelines and health care policy decisions. NCCIH also has interest in supporting randomized pragmatic clinical trials that enroll a generalizable population from real-world settings and leverage data from electronic health records. It is important that the interventions proposed for pragmatic and implementation trials have demonstrated efficacy or effectiveness.

What Does Success Look Like?

• Trials supported by NCCIH provide strong evidence for clinical guideline development and health care policy decisions.
• The clinical portfolio comprises a range of clinical trials to assess the impact of nutritional, psychological, and physical approaches, including feasibility trials, randomized controlled efficacy trials, randomized controlled effectiveness trials, randomized controlled pragmatic trials, and dissemination and implementation studies.
• Interventions found to be feasible in early-stage trials are moved into multisite clinical trials to assess their safety and efficacy or effectiveness, and then interventions with demonstrated efficacy or effectiveness are evaluated in pragmatic trials conducted in health care systems, as well as dissemination and implementation studies.
• When appropriate, the portfolio includes trials with innovative designs to address unique hypotheses about which complementary health approaches are most effective, for whom, and under what conditions.
• NCCIH issues notices for clinical trials in specific scientific areas based on scientific need and as funds allow.

Priorities

Intervention Translation and Development

• Support trials of natural products, including probiotics, to assess whether the impacts of these products on biological signature(s) are reproducible.
• Support development of manualized intervention manuals of integrated multicomponent therapies and systems and feasibility testing of these manualized interventions.

Intervention Refinement and Feasibility Testing

• Encourage multisite pilot studies to demonstrate an intervention is feasible across sites.

Intervention Testing

• For nutritional approaches: Support fully powered randomized controlled efficacy trials when preliminary data demonstrate the nutritional intervention (e.g., natural product) produces a reproducible impact on a biological signature(s).
• For research on psychological and/or physical approaches: Support fully powered randomized controlled efficacy or effectiveness trials when preliminary data demonstrate the single or multicomponent intervention(s) can be delivered with fidelity and participant adherence across sites.
• Encourage pragmatic clinical trials of nutritional, psychological, and/or physical interventions that have demonstrated efficacy or effectiveness to determine whether the interventions remain effective when they are integrated into health care systems.
• When research hypotheses call for it, use innovative or adaptive study designs.

Dissemination and Implementation Studies

• Support research studies to determine how to disseminate or implement complementary health approaches that have established efficacy into clinical or community-based care settings, using dissemination and implementation science methodology (see Implementation Science priority topic for more information).