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Considerations in (clinical) CAM Research

Dr. Ather Ali, ND, MPH, MHS (c)Associate Research Scientist, Department of PediatricsIntegrative Medicine Specialist, Yale Stress CenterDirector, Integrative Medicine at Yale

Atatürk ÜniversitesiMay 2014

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Outline

• Assumptions and Values• Specific Considerations • Outcomes in CAM Research• Opposite of Drug Development Model• Control group considerations

– Examples of massage, dietary interventions• Ethical issues

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Fundamental assumptions

• Health claims can be tested systematically• Randomized controlled trials are one (of many) ways to

assess outcomes• It is possible to conduct rigorous randomized trials of

CAM

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Fundamental Values of Research

• Beneficience: A social commitment to public welfare. In terms of medical therapies, a commitment to public welfare is the obligation to generate and provide to health care practitioners, policy makers, and the public access to the best information available on the efficacy of CAM therapies.

• Nonmaleficence: A commitment to protect patients and the public generally from hazardous medical practices and to inform practitioners, policy makers, and the public of select therapeutic modalities that are potentially injurious or deleterious to health

• Autonomy: Autonomy expresses the interest in allowing and actively enabling individuals to make knowing and voluntary choices in health care, in accord with their own values

Institute of Medicine (US) Committee on the Use of Complementary and Alternative Medicine by the American Public. Complementary and Alternative Medicine in the United States. Washington (DC): National Academies Press (US); 2005.

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Fundamental Values

• Medical pluralism: Serious consideration of the safety, efficacy, and potential integration of CAM therapies into conventional medicine means acknowledgement of multiple valid modes of healing and a pluralistic foundation for health care. Many CAM practices are rooted, at least in part, in forms of evidence and logic other than those used in biomedical sciences, often with long traditions and theoretical systems of interpretation divergent from those used in biomedicine.

• “Therapies that might be highly effective within the proper cultural and belief context might prove to be totally ineffective within the foreign environment required for and created by the conduct of an randomized controlled trial”

Institute of Medicine (US) Committee on the Use of Complementary and Alternative Medicine by the American Public. Complementary and Alternative Medicine in the United States. Washington (DC): National Academies Press (US); 2005.

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Considerations in CAM Research

• Some CAM providers would prefer that their healing traditions remain outside conventional systems of care and reimbursement

• Companies that have successfully marketed a CAM product– Possible philosophical reservations– little or no financial incentive to rigorously / independently

test • Single components vs. studies of systems/multiple

interventions– balance internal validity with external generalizability

• Whole systems research• Efficacy vs. effectiveness

– What question are you trying to answer?• Bias and vested interests

– The goal to “prove that something works”• Expectations

Deng G, Weber W, Sood A, Kemper K. Integrative Medicine Research: Context and Priorities. Commissioned paper for Institute of Medicine (IOM) of the National Academies. Summit on Integrative Medicine and the Health of the Public. 2009.

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Outcomes to consider

• “Optimal health” = well-being of the whole person—physical, mental, social, and spiritual

• Incorporating individual patient preferences in considering appropriate study outcomes – Community-based participatory research (CBPR) is an

applied collaborative approach that enables community residents to more actively participate in the full spectrum of research (from conception – design – conduct – analysis – interpretation – conclusions – communication of results) with a goal of influencing change in community health, systems, programs or policies.

• Quality of life and more “holistic” outcomes– morbidity, mortality, cost of care, and patient satisfaction, but

also the impact of care on family cohesiveness, cultural identity, spiritual beliefs, resilience, coping, and self-efficacy.

• “Alternative Therapies, not Alternative Outcomes”Deng G, Weber W, Sood A, Kemper K. Integrative Medicine Research: Context and Priorities. Commissioned paper for Institute of Medicine (IOM) of the National Academies. Summit on Integrative Medicine and the Health of the Public. 2009.

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Outcomes - 2

• Patient outcomes – Mortality rates, years of life saved – Morbidity—physical, psychological, emotional and social

symptoms; severity of illness – Health behaviors—dietary, exercise patterns; smoking,

drinking, and drug use– Health care utilization (self / CAM / conventional care)– Satisfaction with care – Developmental milestones and behavior – Activities of daily living / Quality of Life– Costs associated with care – Direct and indirect financial costs; opportunity costs of

missed treatments; side effects; adverse interactions with other therapies; toxic exposures

– Social outcomes (work/school missed; delinquency, incarceration)

Deng G, Weber W, Sood A, Kemper K. 2009.

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Outcomes - 3

• Family outcomes – Days of work missed; out-of-pocket costs– Psychosocial impact on families; empowerment

• Spiritual outcomes– coping, peace, serenity, harmony in relationships, a sense of

meaning or purpose in life, self-efficacy, self-esteem• Social outcomes

– divorce, employment, bankruptcy • Community outcomes

– Sense of cohesiveness, cultural identity ; social capital – Cost to society

• Environmental impact– cost of remedy to society, environment, (overharvesting of

herbs leading to extinction; climate change; pollution) • Provider outcomes

– Provider satisfaction with role – Burnout

Deng G, Weber W, Sood A, Kemper K. 2009.

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Outcomes -4

• Use of high-tech assessments– fMRI / PET and meditation– psychoendoneuroimmunology – genomics and lifestyle interventions (Ornish)

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Clinical CAM Research vs. Drug Development

Pharmaceutical Research and Manufacturers of America

MAINSTREAM DRUG DEVELOPMENT

CAM CLINICAL TRIALS

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Opposite of Drug Development

• Some argue that effectiveness/pragmatic studies should occur prior to rigorous randomized controlled trials

• If the system of integrative medicine is found to be effective– future studies can then examine the components of the whole

system– individual components can be assessed for biological

mechanism

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Control Groups

• blinding participants to the study hypothesis• sham training approaches• sham procedures

– sham acupuncture / sham massage• similar attention-control interventions

– Mindfulness based stress reduction and Stress Management Education

• blinding of outcome assessors

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Ethical issues

• Only interventions with a high potential for efficacy should be tested– those with a high public health impact

• Ethical imperative– to provide therapeutic options that are safe and effective for

symptomatic relief– appropriate informed consent– without endorsing approaches that are unsafe or ineffective

Deng G, Weber W, Sood A, Kemper K. 2009.

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Other useful designs

• Epidemiological studies– Patient registries in CAM clinics

• Health services research– how providers practice – what patients seek care – the benefit patients receive– cost effectiveness of integrative medicine

Deng G, Weber W, Sood A, Kemper K. 2009.

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Contextual / Nonspecific / Placebo effects

• Important with subjective outcomes such as in chronic pain syndromes

• Stronger with alternative therapies associated with elaborate rituals and distinct contexts

• Emerging literature on the psychobiology of the placebo effect– clinically significant effects demonstrated in a variety of

contexts– intentional use of placebo in clinical practice is routine– ethical implications

Ali A, McCarthy P. Complementary and Integrative Methods in Fibromyalgia. Pediatrics in Review. 2014.

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Disclosed vs. undisclosed placebo

• Placebo and Medication Effects in Episodic Migraine • In a randomized order over six consecutive attacks, 66 patients

with episodic migraine received either placebo or 10-mg rizatriptan under three information conditions

Sci Transl Med 6, 218ra5 (2014)

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Research Priorities for Integrative Medicine

• Conditions, Diseases, and Health Behaviors – Impose a heavy burden of suffering on individuals, families or

the community either because of their • severity • chronicity • prevalence

• Current mainstream therapies are unacceptable or insufficient – lack of proven efficacy – substantial side effects – cost– lack of availability

• IM offers a reasonable likelihood of being helpful based on – safety in animal models – lengthy historical use or compelling results from case

reports, case series, epidemiologic studies, case-control trials or cohort studies, or clear scientific rationale

• When people are already using integrative approaches

Deng G, Weber W, Sood A, Kemper K. 2009.

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Resources

• NCCAM Clinical Research Toolbox– http://nccam.nih.gov/grants/toolbox

• International Society for Complementary Medicine Research (ISCMR)– http://www.iscmr.org

• Clinical Research in Complementary Therapies (Lewith / Jonas / Wallach)

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This work was supported by a grant from

National Center for Complementary and Alternative MedicineNational Institutes of HealthU.S. Department of Health and Human Serviceswww.nccam.nih.gov