Abstract
Background: The translation of clinical practice into research presents unique challenges. This is especially the case in evaluating the effect of interventions in the management of chronic conditions such as pain, mental health, substance misuse, and oncology care. Chronic complex conditions might respond to different strategies at different points in time and may require an interdisciplinary approach to treatment.
Objectives: To define the key barriers to the design, implementation, and evaluation of clinical trials of acupuncture that derive from a unidirectional translational research strategy.
Results: Critical challenges to the design, implementation, and evaluation of clinical trials of acupuncture center around four areas: (1) insufficient early phase research, (2) suboptimal treatment protocols, (3) inadequate research questions, and 4) a narrowed assessment of outcomes.
Conclusions: By promoting research priorities that reflect the complex nature of chronic illness, we can more clearly articulate research questions that better reflect clinical practice, while evaluating the impact of acupuncture in patient care. Key priorities include phase I research funding opportunities, pragmatic trials that evaluate acupuncture embedded in interprofessional teams, and the inclusion of hypothesis-driven secondary outcomes.
Keywords: acupuncture, chronic illness management, dose response, interprofessional teams, hypothesis-driven outcomes
Introduction
The translation of insights derived from clinical practice into research presents unique challenges. This is especially the case in evaluating interventions in the management of chronic conditions, which respond to different strategies at different time points1 and require an interdisciplinary approach to treatment. Asking whether acupuncture as a monotherapy is effective overlooks the multifactorial nature of these problems. It misses the opportunity to explore whether synergistic treatment strategies provided by interprofessional care teams, which include acupuncturists, may have a significant impact on clinical outcomes.2
Critical challenges to the design, implementation, and evaluation of clinical trials of acupuncture derive from an inadequate unidirectional translational research strategy. Insights derived from clinical practice need to inform the design of clinical trials in as much as insights derived from mechanisms do. In acupuncture research, these challenges center around four areas: (1) insufficient early phase research, (2) suboptimal treatment protocols, (3) unclear research questions, and (4) a narrowed assessment of outcomes.
A dearth of funding mechanisms and lack of recognition of the critical importance of early phase research in acupuncture have led to premature abandonment of research areas with potential promise.3 A tendency to bypass early phase clinical research for phase 2 trials has resulted in the implementation of study designs that have not addressed what is needed in evaluating a complex modality such as acupuncture, for example, acupuncture's unique characteristics, or the specific condition, or particular cohort that is being evaluated. Unlike clinical trials of pharmacotherapy, there are no guidelines and few funding mechanisms for feasibility studies of acupuncture. Innovative new program announcements are promising in reversing this trend (PAR-18-417).4
Although the purpose of early phase research is to identify promising areas that merit further investigation and ensure that resources are allocated to interventions that are feasible, acceptable, and appear to provide benefit, the field has applied statistical criteria targeted at evaluating phase 2/3 trials, which are inappropriate for early phase research.3 As a result, many trials are too small and underpowered, and even though they may be presented as “pilot” studies, the results are expected to show significance using P-values, which constitutes a major reason for the abundance of “negative” or inconclusive results. Consequently, few trials are replicated, and given that very few areas of research have been sufficiently studied, it has been concluded that the application of acupuncture is limited to the treatment of pain and symptom management in cancer care. Less is known about other key areas including mental health and substance/medication abuse and misuse.
Acupuncture protocols tested in clinical trials are often oversimplified and modified to the extent that they may not reflect clinical practice and may provide suboptimal treatment. The wide variety of acupuncture styles, coupled with a lack of a consensus of what constitutes best treatment and sparse early phase research, may have resulted in an ad hoc selection of protocols primarily based on convenience, prior experience of one of the investigators, ease of implementation, or available resources. In addition, overcoming the ambiguity of the term acupuncture is a critical step in advancing scientific inquiry into its potential benefit.5 Furthermore, we do not know what exactly constitutes adequate dose in acupuncture.6 The reliable implementation of acupuncture protocols that account for individual patient differences while maintaining replicability and standardization can be achieved by manualizing the protocols and training the treatment providers on the systematic implementation of the protocol regardless of the rationale or style of treatment.7
Acupuncture is a complex, multimodal, and highly heterogeneous treatment intervention. Although there is still no conclusive evidence regarding which individual components of acupuncture treatment are directly associated with therapeutic benefit or for what conditions or patient populations, one can assume that these differences introduce an artifact in the evaluation of outcomes, especially in smaller sham-controlled trials. Furthermore, acupuncture trials for the same condition, even with similar cohorts, are rarely equivalent in design, analysis, or outcome measures. This has resulted in inconclusive results even from some of the most rigorous meta-analyses and systematic reviews.8
The symptom cluster framework9,10 may be helpful in modeling an assessment of acupuncture's potential in the care of patients with chronic pain, cancer, mental health issues, and substance/medication abuse/misuse, as well as other complex chronic conditions. Although different sets of clusters have been identified in different cohorts,1,8,9 many chronic conditions share common symptoms in the areas of fatigue, pain, psychoneurologic function (including sleep, emotional regulation, and cognitive dysfunction), and functional gastrointestinal disorders. In complex chronic conditions, acupuncture treatment may significantly augment the effect of established treatments, increasing compliance, optimizing outcomes, managing symptoms, and reducing side effects. Although further research is needed, it is timely to assess whether acupuncture has a critical role to play in reducing symptom burden in chronically ill patients and improving their capacity to manage a chronic condition.
Discussion
Research into acupuncture's mechanisms may reveal an underlying regulatory physiology that helps the system recalibrate when confronted with persistent or undue stress, whether physiologic or psychosocial (R. Hammerschlag, pers. comm. January 2019). Therefore, it is critical to emphasize research designs that help us understand whether acupuncture may alter the timing of symptoms and trajectory of illness, and whether it does so by decreasing allostatic load, regulating sympathetic tone, and optimizing physiologic function. Furthermore, it is critical to assess whether the inclusion of acupuncture in patient care can significantly contribute to enhancing self-efficacy, increasing health-promoting behaviors, fostering personal agency, improving quality of life, and supporting patient empowerment as they regain a sense of control over their own lives. We cannot continue to imply that these are nonspecific placebo effects, as it is well known that these factors are critical in achieving positive clinical outcomes.11
Conclusions
Recommendations for optimizing a bidirectional research strategy would include to (1) prioritize the development of small phase I trials that explore feasibility, determine optimal protocols, and establish dose response; (2) expand research questions to assess the role of acupuncture embedded in interprofessional teams (especially when assessing the management of complex chronic conditions); and (3) evaluate change over time in symptom management, health promotion, and quality of life in response to acupuncture treatment.
Author Disclosure Statement
No competing financial interests exist.
Funding Information
No funding was received for this article.
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