Blackman Rev021505

Evaluation of Complementary and Alternative Therapies: 

Evaluation of Complementary and Alternative Therapies Marc R. Blackman, M.D. Chief, Endocrine Section LCI, DIR, NCCAM Principles and Practice of Clinical Research February 15, 2005

Slide2: 

Nature, Use, and Claims of CAM Conducting CAM Research Ethical Issues in CAM Presentation Overview

What Is CAM?: 

… medical and health care practices outside the realm of conventional medicine, which are yet to be validated using scientific methods What Is CAM? Complementary: together with conventional practices Alternative: in place of conventional practices

CAM Modalities Now in Mainstream Medicine: 

CAM Modalities Now in Mainstream Medicine Codeine for pain Digitalis for heart failure Ipecac for poisoning Quinine for malaria Aspirin for fever Behavioral therapy for headache Hypnosis for smoking cessation Low fat, low cholesterol diets Exercise for diabetes Support groups for breast cancer

The CAM Domains: 

The CAM Domains

The Appeal of CAM: 

The Appeal of CAM Media reports of dramatic results Belief that CAM treatments are natural Patient empowerment Focus on spiritual and emotional well-being Therapist providing “touch, talk, time”

CAM Use in the United States: 

CAM Use in the United States 62% of adults 18+ used CAM in the past year More women than men; higher educated; sicker; with more pain Top 10: 43% prayed for self 24% others prayed for you 19% natural products 12% deep breathing exercises 10% participate in prayer group 8% meditation 8% chiropractic 5% yoga 5% massage 4% diet-based therapies Barnes et al., CDC ADR, 2004

NCCAM’s Mission: 

NCCAM’s Mission Conduct rigorous research on CAM practices Train CAM researchers Inform consumers and health professionals

Who Is the Practitioner?: 

Who Is the Practitioner? Medical doctors CAM practitioners Traditional healers

CAM Economics: 

CAM Economics Americans spend more out-of-pocket for CAM than for all other health care needs CAM is big business 56% of Americans believe their health plans should cover CAM Many health insurers and HMOs now cover CAM: Blue Cross of Washington and Alaska, Oxford Health, Prudential, Kaiser Permanente

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Who uses CAM? More educated In poorer health More affluent Possess a holistic orientation to health Had a ‘transformational experience’ Identification with environmentalism, feminism, spirituality Report chronic anxiety, pain, UTI, back problems (Astin et al. JAMA ,1998)

Biological Research - It’s All “Natural”…!: 

Biological Research - It’s All “Natural”…! “People can be induced to swallow anything, provided it is sufficiently seasoned with praise.” Jean Moliere

Dietary Supplements: DSHEA Definition: 

Dietary Supplements: DSHEA Definition Product intended to supplement the diet Contains one or more of the following: Vitamin Mineral Herb or other botanical (not tobacco) Amino acid Any other dietary substance For oral intake as a concentrate, metabolite, extract, constituent, or combination

Patterns of Supplement Use:The Slone Survey: 

Patterns of Supplement Use: The Slone Survey 2590 participants 18 years + Telephone survey, random sample Feb 1998 - Dec 1999 In the preceding week: 14% of population used herbals and/or supplements 16% of prescription drug users used herbals and/or supplements JAMA, 2002

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Patterns of Supplement Use: The Slone Survey Ginseng Ginkgo biloba Allium sativum Glucosamine St. John’s wort Echinacea Lecithin Chondroitin Creatine Serenoa repens Ten Most Commonly Used Herbals / Supplements JAMA, 2002

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Patterns of Supplement Use: The Slone Survey General health/good for you (16%) Arthritis (7%) Memory improvement (6%) Energy (5%) Immune booster (5%) Joints (4%) Supplement diet (4%) Sleep aid (3%) Prostate (3%) No reason (2%) All other reasons (45%) Ten Most Common Reasons for taking herbs / supplements JAMA, 2002

Challenges of Herbal Medicines: 

Challenges of Herbal Medicines Safety is assumed, not proven Lack of product standardization Contamination with drugs, heavy metals Allergic reactions Inherent toxicity Interactions with drugs Replacing proven therapies

Ephedra: Safety Concerns: 

Ephedra: Safety Concerns Ma huang (Ephedra sineca) – Short-term TCM treatment for asthma, decongestion Contains L-ephedrine, pseudoephedrine Major current use in U.S. in combination with caffeine for weight loss, athletic performance Dozens of reports of severe and life-threatening adverse events in young people

Environmental Challenges: 

Environmental Challenges Important public health issues Inconsistent training, credentialing, licensure, access, regulation, reimbursement Highly variable products and product standards

Slide20: 

Nature, Use, and Claims of CAM Conducting CAM Research Ethical Issues in CAM Presentation Overview

NCCAM’s Strategic Areas: 

NCCAM’s Strategic Areas Investing in research Training CAM investigators Expanding outreach Facilitating integration

NCCAM’s Unique Scientific Challenge: Conducting Rigorous Research: 

NCCAM’s Unique Scientific Challenge: Conducting Rigorous Research Broad spectrum of CAM practices Inconsistent product and practice standards Few CAM practitioners experienced in research Market disincentives Dearth of credible scientific information

Challenges of Natural Products Research: 

Challenges of Natural Products Research Safety is assumed, not proven Products are not standardized Contamination with drugs and heavy metals Allergic reactions Some are toxic Interactions with drugs Replacing proven therapies

Prioritizing Studies: 

Prioritizing Studies Public health needs Preliminary data exist Good products available Feasible studies Ethical studies Systematic Reviews

Major Research Areas: 

Major Research Areas

The Research PortfolioBy major public health conditions: 

The Research Portfolio By major public health conditions

The Research Portfolio: NCCAM’s Ongoing Phase III Trials: 

The Research Portfolio: NCCAM’s Ongoing Phase III Trials

fMRI Pinpoints Central Effects of Acupuncture: 

fMRI Pinpoints Central Effects of Acupuncture Hui, K. et al., MGH, NMR Center

The Placebo: 

The Placebo Historically, an inactive or innocent management contrivance to encourage healing in the absence of specific therapeutics Relied upon to ‘control’ for nonspecific effects that might confound calculation of the true benefits of a novel intervention

This Is Your Brain on Placebo: 

This Is Your Brain on Placebo Petrovic, PP et al. Science Express Reports, 2002 Placebo and Opioid Analgesia - Imaging a Shared Neuronal Network rostral anterior cingulate cortex

Acupuncture for Knee Osteoarthritis: Fulfilling the Vision for Rigorous CAM Studies: 

Acupuncture for Knee Osteoarthritis: Fulfilling the Vision for Rigorous CAM Studies

Ginkgo Biloba:Prevention Trial for Dementia: 

Ginkgo Biloba: Prevention Trial for Dementia

Grantee Research: Studying Cellular Mechanisms of Ginkgo Biloba: 

Grantee Research: Studying Cellular Mechanisms of Ginkgo Biloba Increases stress resistance and extends the lifespan of C.elegans J Smith, et al., Cellular and Mol Biol, 2002 Protects cultured neural cells from undergoing apoptosis Z Wu, J Smith, et al., Cellular and Mol Biol, 2002 Inhibits beta-amyloid aggregration A recent trio of studies determined that Ginkgo extract: Y Luo, J Smith, et al., Proc Natl Acad Sci USA, 2002

Women’s Health: Better Management of Menopausal Transition: 

Women’s Health: Better Management of Menopausal Transition Supporting research on CAM modalities for hot flashes, other menopausal symptoms Convened workshop to assess existing tools for measurement of hot flashes (January 2004) With NIH, NIBIB, & ORWH, issued RFA for SBIR applications to improve objective measures of hot flashes (September 2004) Cosponsoring, with NIA, state-of-the-science conference on Management of the Menopausal Transition (March 2005) Clinical trials to follow

NCCAM Is Active in Major Trans-NIH Initiatives: 

NCCAM Is Active in Major Trans-NIH Initiatives Osteoarthritis Obesity Neuroscience Blueprint NIH Roadmap for Medical Research

IOM Study on CAM: 

IOM Study on CAM NCCAM and 16 NIH ICs and AHRQ commissioned the study in 2002 Panel asked to address a wide range of CAM science, policy, and practice issues Study released on January 12, 2005

IOM Study on CAM: 

IOM Study on CAM Key Conclusions Same principles and standards of evidence of treatment effectiveness should apply to all conventional and CAM interventions Emphasize health services research and consider ethical, legal, and social implications of CAM research and integrated medicine Ensure rigor in CAM studies

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Key Principles of CAM Research Use the same designs and outcome instruments as for definitive studies of conventional practices Randomized, double-blind controlled trials are the ‘gold standard’ Some modalities can not be blinded Studies of whole CAM ‘systems’ require creativity and flexibility CAM experts and patient advocates should be included in study design and oversight

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Designing CAM Studies Individual botanical or nutritional supplements can be tested in randomized, double-blind controlled trials. Combinations of agents, especially if custom-tailored for each subject are harder to blind. Complex CAM systems and physical modalities, among others, can not be blinded It is hard to study the approach of an individual practitioner

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Issues in Studies of CAM Treatments Complex and multi-modal Individualized regimens Intra- and inter-practitioner consistency Acceptability of randomization Test materials of highly variable potency Use of placebo and sham treatment arms

Training CAM Investigators: 

Training CAM Investigators Tailor programs to reflect evolving needs Foster a culture of research Provide resources to build careers in CAM research

NCCAM Training Opportunities: 

NCCAM Training Opportunities The Challenge: Finding Good Mentors

Integrating CAM Education into Conventional Medical Curricula: 

Integrating CAM Education into Conventional Medical Curricula Settings: 15 medical, nursing, pharmacy, osteopathy, dental schools Funding: Up to $300K per year each for 5 years through R25 grants Goal: Integrate information on CAM practices into academic curricula

CAM Research Resultsin Mainstream Publications: 

CAM Research Results in Mainstream Publications Funded over 800 projects Over 700 scientific publications Publications have appeared in journals such as JAMA, Lancet, NEJM, Annals of Internal Medicine and PNAS Grantee bibliography available on NCCAM Web site

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Launched: February 2001 Contains nearly 300,000 citations Access via NCCAM Web site: Click on icon CAM on PubMed Access via NLM’s PubMed: Complementary Medicine Subset

Communications Information and Outreach: 

Communications Information and Outreach NCCAM Web Site More than 1.5 million visitors a year Information Clearinghouse Inquiries by phone, email, fax, letters Newsletter, E-Bulletin More than 11,000 subscribers CAM on PubMed 5,800 user sessions per month Patient Recruitment 800-number, promotion, patient ed pamphlets Public Education More than 90 fact sheets, reports, alerts, and other information products Town Meetings, Exhibits, Lectures Events nationwide

Slide47: 

Nature, Use, and Claims of CAM Conducting CAM Research Ethical Issues in CAM Presentation Overview

Requirements for Ethical Research: 

Requirements for Ethical Research Social value Scientific validity Fair subject selection Favorable risk:benefit ratio Independent review Informed consent Respect study subjects Emmanuel, Wendler & Grady, JAMA, 2000

Ethical Issues Posed by CAM: 

Ethical Issues Posed by CAM Social value Extensive public use without proof Emerging evidence questions traditional assumptions of safety and efficacy Scientific validity The literature is dominated by under-powered, poorly designed studies, conducted by people with limited scientific credentials

Slide50: 

The plural of anecdote is not evidence

Critique of Ongoing CAM Research: 

Critique of Ongoing CAM Research Sets a higher standard than for conventional practices – few allopathic practices are proven with double-blind RCTs Is too reductionistic – CAM is multi-modal Does not test the approach as traditionally delivered – wrong herb; wrong dose; wrong needling point … The investigators have no expertise in CAM

Ethical Issues Posed by CAM : 

Ethical Issues Posed by CAM Fair subject selection Advocates and skeptics refuse enrollment, comply poorly and withdraw prematurely These biases risk the generalizability of the study findings Risk:benefit ratio Lack of formal preclinical and clinical data challenges assumptions of safety, optimal dose and schedule

Ethical Issues Posed by CAM : 

Ethical Issues Posed by CAM Independent review IRBs may oppose or lack expertise in CAM Informed consent Undermines expectations of healing Difficult to inform where objective data on potential risks and benefits are lacking Respect for subjects Cannot ethically study everything to which a person is willing to be subjected

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Practices or placebo arm would displace life-saving therapies Irreproducible products Unsafe practices or products Unethical Studies

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Nature, use, and claims of CAM Conducting CAM Research Ethical Issues in CAM Summary

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National Center for Complementary and Alternative Medicine National Institutes of Health Department of Health and Human Services w w w . n c c a m . n i h . g o v