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Guidance for Institutional Review Boards and Clinical Investigators
Before a new drug or biologic can be marketed, its sponsor must show, through adequate and well-controlled clinical studies, that it is effective. A well-controlled study permits a comparison of subjects treated with the new agent with a suitable control population, so that the effect of the new agent can be determined and distinguished from other influences, such as spontaneous change, "placebo" effects, concomitant therapy, or observer expectations. FDA regulations [21 CFR 314.126] cite five different kinds of controls that can be useful in particular circumstances:
No general preference is expressed for any one type, but the study design chosen must be adequate to the task. Thus, in discussing historical controls, the regulation notes that, because it is relatively difficult to be sure that historical control groups are comparable to the treated subjects with respect to variables that could effect outcome, use of historical control studies has been reserved for special circumstances, notably cases where the disease treated has high and predictable mortality (a large difference from this usual course would be easy to detect) and those in which the effect is self-evident (e.g., a general anesthetic).
Placebo control, no-treatment control (suitable where objective measurements are felt to make blinding unnecessary), and dose-comparison control studies are all study designs in which a difference is intended to be shown between the test article and some control. The alternative study design generally proposed to these kinds of studies is an active-treatment concurrent control in which a finding of no difference between the test article and the recognized effective agent (active-control) would be considered evidence of effectiveness of the new agent. There are circumstances in which this is a fully valid design. Active-controls are usually used in antibiotic trials, for example, because it is easy to tell the difference between antibiotics that have the expected effect on specific infections and those that do not. In many cases, however, the active-control design may be simply incapable of allowing any conclusion as to whether or not the test article is having an effect.
There are three principal difficulties in interpreting active-control trials. First, active-control trials are often too small to show that a clinically meaningful difference between the two treatments, if present, could have been detected with reasonable assurance; i.e., the trials have a high "beta-error." In part, this can be overcome by increasing sample size, but two other problems remain even if studies are large. One problem is that there are numerous ways of conducting a study that can obscure differences between treatments, such as poor diagnostic criteria, poor methods of measurement, poor compliance, medication errors, or poor training of observers. As a general statement, carelessness of all kinds will tend to obscure differences between treatments. Where the objective of a study is to show a difference, investigators have powerful stimuli toward assuring study excellence. Active-control studies, however, which are intended to show no significant difference between treatments, do not provide the same incentives toward study excellence, and it is difficult to detect or assess the kinds of poor study quality that can arise. The other problem is that a finding of no difference between a test article and an effective treatment may not be meaningful. Even where all the incentives toward study excellence are present, i.e., in placebo-controlled trials, effective drugs are not necessarily demonstrably effective (i.e., superior to placebo) every time they are studied. In the absence of a placebo group, a finding of no difference in an active-control study therefore can mean that both agents are effective, that neither agent was effective in that study, or that the study was simply unable to tell effective from ineffective agents. In other words, to draw the conclusion that the test article was effective, one has to know with assurance that the active-control would have shown superior results to a placebo, had a placebo group been included in the study.
For certain drug classes, such as analgesics, antidepressants or antianxiety drugs, failure to show superiority to placebo in a given study is common. This is also often seen with antihypertensives, anti-angina drugs, anti-heart failure treatments, antihistamines, and drugs for asthma prophylaxis. In these situations, active-control trials showing no difference between the new drug and control are of little value as primary evidence of effectiveness and the active-control design (the study design most often proposed as an alternative to use of a placebo) is not credible.
In many situations, deciding whether an active-control design is likely to be a useful basis for providing data for marketing approval is a matter of judgment influenced by available evidence. If, for example, examination of prior studies of a proposed active-control reveals that the test article can very regularly (almost always) be distinguished from placebo in a particular setting (subject population, dose, and other defined parameters), an active-control design may be reasonable if it reproduces the setting in which the active-control has been regularly effective.
It is often possible to design a successful placebo-controlled trial that does not cause investigator discomfort nor raise ethical issues. Treatment periods can be kept short; early "escape" mechanisms can be built into the study so that subjects will not undergo prolonged placebo-treatment if they are not doing well. In some cases randomized placebo-controlled therapy withdrawal studies have been used to minimize exposure to placebo or unsuccessful therapy; in such studies apparent responders to a treatment in an open study are randomly assigned to continued treatment or to placebo. Subjects who fail (e.g., blood pressure rises, angina worsens) can be removed promptly, with such failure representing a study endpoint.
IRBs may face difficult issues in deciding on the acceptability of placebo-controlled and active-control trials. Placebo-controlled trials, regardless of any advantages in interpretation of results, are obviously not ethically acceptable where existing treatment is life-prolonging. A placebo-controlled study that exposes subjects to a documented serious risk is not acceptable, but it is critical to review the evidence that harm would result from denial of active treatment, because alternative study designs, especially active-control studies, may not be informative, exposing subjects to risk but without being able to collect useful information.
- placebo concurrent control
- dose-comparison concurrent control
- no-treatment concurrent control
- active-treatment concurrent control, and
- historical control
No general preference is expressed for any one type, but the study design chosen must be adequate to the task. Thus, in discussing historical controls, the regulation notes that, because it is relatively difficult to be sure that historical control groups are comparable to the treated subjects with respect to variables that could effect outcome, use of historical control studies has been reserved for special circumstances, notably cases where the disease treated has high and predictable mortality (a large difference from this usual course would be easy to detect) and those in which the effect is self-evident (e.g., a general anesthetic).
Placebo control, no-treatment control (suitable where objective measurements are felt to make blinding unnecessary), and dose-comparison control studies are all study designs in which a difference is intended to be shown between the test article and some control. The alternative study design generally proposed to these kinds of studies is an active-treatment concurrent control in which a finding of no difference between the test article and the recognized effective agent (active-control) would be considered evidence of effectiveness of the new agent. There are circumstances in which this is a fully valid design. Active-controls are usually used in antibiotic trials, for example, because it is easy to tell the difference between antibiotics that have the expected effect on specific infections and those that do not. In many cases, however, the active-control design may be simply incapable of allowing any conclusion as to whether or not the test article is having an effect.
There are three principal difficulties in interpreting active-control trials. First, active-control trials are often too small to show that a clinically meaningful difference between the two treatments, if present, could have been detected with reasonable assurance; i.e., the trials have a high "beta-error." In part, this can be overcome by increasing sample size, but two other problems remain even if studies are large. One problem is that there are numerous ways of conducting a study that can obscure differences between treatments, such as poor diagnostic criteria, poor methods of measurement, poor compliance, medication errors, or poor training of observers. As a general statement, carelessness of all kinds will tend to obscure differences between treatments. Where the objective of a study is to show a difference, investigators have powerful stimuli toward assuring study excellence. Active-control studies, however, which are intended to show no significant difference between treatments, do not provide the same incentives toward study excellence, and it is difficult to detect or assess the kinds of poor study quality that can arise. The other problem is that a finding of no difference between a test article and an effective treatment may not be meaningful. Even where all the incentives toward study excellence are present, i.e., in placebo-controlled trials, effective drugs are not necessarily demonstrably effective (i.e., superior to placebo) every time they are studied. In the absence of a placebo group, a finding of no difference in an active-control study therefore can mean that both agents are effective, that neither agent was effective in that study, or that the study was simply unable to tell effective from ineffective agents. In other words, to draw the conclusion that the test article was effective, one has to know with assurance that the active-control would have shown superior results to a placebo, had a placebo group been included in the study.
For certain drug classes, such as analgesics, antidepressants or antianxiety drugs, failure to show superiority to placebo in a given study is common. This is also often seen with antihypertensives, anti-angina drugs, anti-heart failure treatments, antihistamines, and drugs for asthma prophylaxis. In these situations, active-control trials showing no difference between the new drug and control are of little value as primary evidence of effectiveness and the active-control design (the study design most often proposed as an alternative to use of a placebo) is not credible.
In many situations, deciding whether an active-control design is likely to be a useful basis for providing data for marketing approval is a matter of judgment influenced by available evidence. If, for example, examination of prior studies of a proposed active-control reveals that the test article can very regularly (almost always) be distinguished from placebo in a particular setting (subject population, dose, and other defined parameters), an active-control design may be reasonable if it reproduces the setting in which the active-control has been regularly effective.
It is often possible to design a successful placebo-controlled trial that does not cause investigator discomfort nor raise ethical issues. Treatment periods can be kept short; early "escape" mechanisms can be built into the study so that subjects will not undergo prolonged placebo-treatment if they are not doing well. In some cases randomized placebo-controlled therapy withdrawal studies have been used to minimize exposure to placebo or unsuccessful therapy; in such studies apparent responders to a treatment in an open study are randomly assigned to continued treatment or to placebo. Subjects who fail (e.g., blood pressure rises, angina worsens) can be removed promptly, with such failure representing a study endpoint.
IRBs may face difficult issues in deciding on the acceptability of placebo-controlled and active-control trials. Placebo-controlled trials, regardless of any advantages in interpretation of results, are obviously not ethically acceptable where existing treatment is life-prolonging. A placebo-controlled study that exposes subjects to a documented serious risk is not acceptable, but it is critical to review the evidence that harm would result from denial of active treatment, because alternative study designs, especially active-control studies, may not be informative, exposing subjects to risk but without being able to collect useful information.
Clinical Practice Guidelines
“Clinical practice guidelines are systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances.” (Institute of Medicine, 1990)
Issued by third-party organizations, and not NCCIH, these guidelines define the role of specific diagnostic and treatment modalities in the diagnosis and management of patients. The statements contain recommendations that are based on evidence from a rigorous systematic review and synthesis of the published medical literature.
These guidelines are not fixed protocols that must be followed, but are intended for health care professionals and providers to consider. While they identify and describe generally recommended courses of intervention, they are not presented as a substitute for the advice of a physician or other knowledgeable health care professional or provider.
Featured Guidelines
“Clinical practice guidelines are systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances.” (Institute of Medicine, 1990)
Issued by third-party organizations, and not NCCIH, these guidelines define the role of specific diagnostic and treatment modalities in the diagnosis and management of patients. The statements contain recommendations that are based on evidence from a rigorous systematic review and synthesis of the published medical literature.
These guidelines are not fixed protocols that must be followed, but are intended for health care professionals and providers to consider. While they identify and describe generally recommended courses of intervention, they are not presented as a substitute for the advice of a physician or other knowledgeable health care professional or provider.
Featured Guidelines
- Travelers’ Health: Clinician Resources (CDC)
- Institute of Medicine's Report Clinical Practice Guidelines We Can Trust (IOM)
- Standards for Developing Trustworthy Clinical Practice Guidelines (link is external) (IOM)
- National Guideline Clearinghouse (AHRQ)
- Allergic Rhinitis (link is external) (American Academy of Otolaryngology)
- Allergic Rhinitis (link is external) (American Academy of Otolaryngology) [ PDF]
- Allergic Rhinitis and Its Impact on Asthma (ARIA) Guidelines: 2010 Revision (link is external) (Journal of Allergy and Clinical Immunology) [171KB PDF]
- Diagnosis and Management of Food Allergy (link is external) (Journal of Allergy and Clinical Immunology) [165KB]
- Guidelines for the Diagnosis and Management of Asthma (NHLBI)
- Management of Stable Ischemic Heart Disease (link is external) (Annals of Internal Medicine) [ PDF]
- Soy Protein, Isoflavones, and Cardiovascular Health (link is external) (Circulation)
- Vitamin, Mineral, and Multivitamin Supplements for the Primary Prevention of Cardiovascular Disease and Cancer (link is external) (USPSTF)
- 2011–2012 Influenza Antiviral Medications: Summary for Clinicians (CDC)
- American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention (link is external) (CA: Cancer J Clin) [450KB PDF]
- Clinical Use of Dietary Supplements and Nutraceuticals (link is external) (Endocrine Practice) [945KB PDF]
- Dietary Reference Intakes for Calcium and Vitamin D (link is external) (Institute of Medicine of the National Academies)
- Evaluation and Management of Chronic Insomnia in Adults (link is external) (Sleep) [863KB PDF]
- Guidance for Clinicians on the Use of Rapid Influenza Diagnostic Tests (CDC)
- Guidance for the Prevention and Control of Influenza in the Peri- and Postpartum Settings (CDC)
- NSAIDs and Other Complementary Treatments for Episodic Migraine Prevention in Adults (link is external) (Neurology) [393KB PDF]
- Practice Parameters for the Nonpharmacologic Treatment of Chronic Insomnia (Sleep)
- Psychological and Behavioral Treatment of Insomnia (link is external) (Sleep) [279KB PDF]
- Recommendations on Immunization (CDC)
- Treating Tobacco Use and Dependence: 2008 Update (AHRQ) [2MB PDF]
- Vitamin D and Calcium Supplementation to Prevent Fractures in Adults (link is external) (U.S. Preventive Services Task Force)
- Evidence-Based Recommendations on Management of Irritable Bowel Syndrome (link is external) (American Family Physician)
- Probiotics and Children (link is external) (Journal of Pediatric Gastroenterology and Nutrition) [119KB PDF]
- Management of Benign Prostatic Hyperplasia (BPH) (link is external) (American Urological Association) [1.1MB PDF]
- Alternative Therapies for Parkinson's Disease (link is external) (Neurology) [361KB PDF]
- Complementary and Alternative Medicine in Multiple Sclerosis (link is external) (American Academy of Neurology)
- Practice Parameter: Neuroprotective Strategies and Alternative Therapies for Parkinson Disease (An Evidence-Based Review) (link is external) (Neurology)
- Exercise Guidelines for Cancer Survivors (link is external) (Med Sci Sports Exerc)
- Use of Integrative Therapies as Supportive Care in Breast Cancer Patients (link is external) (Journal of the National Cancer Institute) [391KB PDF]
- Adjuvant Treatment of Distal Radius Fractures With Vitamin C (link is external) (American Academy of Orthopaedic Surgeons)
- Use of Supplemental Vitamin D and Calcium in Patients Following Hip Fracture Surgery (link is external) (American Academy of Orthopaedic Surgeons)
- Cannibis in Pain Treatment (link is external) (American Pain Society)
- Chiropractic Management of Fibromyalgia Syndrome: Summary of Clinical Practice (link is external) (Council on Chiropractic Guidelines and Practice Parameters) [21KB PDF]
- Chronic Pain Management (link is external) (Anesthesiology) [699KB PDF]
- Diagnosis and Treatment of Low-Back Pain (link is external) (Annals of Internal Medicine)
- Low Back Pain: Clinical Practice Guidelines Linked to the International Classification of Functioning, Disability, and Health (link is external) (Journal of Orthropaedic and Sports Physical Therapy) [ PDF]
- Management of Fibromyalgia Syndrome in Adults (University of Texas, School of Nursing)
- Management of the Acute Migraine Headache (link is external) (American Family Physician)
- Noninvasive Treatments for Acute, Subacute, and Chronic Low Back Pain (link is external) (Annals of Internal Medicine)
- NSAIDs and Other Complementary Treatments for Episodic Migraine Prevention in Adults (link is external) (Neurology) [393KB PDF]
- Osteopathic Manipulative Treatment for Low-Back Pain (Journal of the American Osteopathic Association)
- Practice Parameter: Evidence-based Guidelines for Migraine Headache (link is external) (Neurology)
- Subluxation Chiropractic Practice (Council on Chiropractic Practice)
- Treatment of Osteoarthritis of the Knee (link is external) (AAOS) [14MB PDF]
- A Practice Pathway for Identification, Evaluation, and Management of Insomnia in Children and Adolescents with Autism Spectrum Disorders (link is external) (Pediatrics)
- Management of Children with Autism Spectrum Disorders (link is external) (Pediatrics)
- Migraine Headaches in Children and Adolescents (Journal of Pediatric Health Care)
- Pediatric Integrative Medicine (link is external) (American Academy of Pediatrics)
- Probiotics and Children (link is external) (Journal of Pediatric Gastroenterology and Nutrition) [119KB PDF]
- Management of Traumatic Stress Disorder and Acute Stress Reaction (VA/DoD)
- Nonpharmacologic Versus Pharmacologic Treatment of Adults With Major Depressive Disorder (link is external) (American College of Physicians)
- Posttraumatic Stress Disorder—Associated Nightmares (Journal of Clinical Sleep Medicine)
- Nonpharmacologic and Pharmacologic Therapies for Osteoarthritis of the Hand, Hip, and Knee (link is external) (American College of Rheumatology) [96KB PDF]
- Osteoarthritis of the Hip and Knee (link is external) (Osteoarthritis Cartilage) [5.2MB PDF]
- Osteoarthritis of the Knee (link is external) (The Journal of the American Academy of Orthopaedic Surgeons) [1.39MB PDF]
- AACE Guidelines for the Diagnosis and Treatment of Menopause (link is external) (Endocrine Practice)
- Botanicals for Menopausal Symptoms (Obstetrics and Gynecology)
- Treatment of Urinary Tract Infections in Nonpregnant Women (ACOG)
Living with Severe Joint Pain | CDC Features
Health Information from NIH
A
A
- Acai
- Acne
- Acupuncture
- Addiction
- ADHD (Attention-deficit Hyperactivity Disorder)
- Adolescents (Teenagers)
- Age-related Macular Degeneration (AMD)
- Aging
- AHRQ Evidence Reports
- Alcohol Addiction
- Alfalfa (MedlinePlus)
- Allergies
- Aloe vera
- Alopecia Areata
- Alpha Lipoic Acid
- Alpha-linolenic Acid
- Alzheimer's Disease
- Antibiotic-associated Diarrhea
- Antioxidants
- Anxiety
- Appetite Suppressant: See
SmartLipo365 Issues Voluntary Nationwide Recall of Smart Lipo Due to Undeclared Sibutramine, Desmethylsibutramine, and Phenolphthalein (FDA;
06/03/15
) - Aristolochic Acids (NIEHS) [229KB PDF]
- Aromatherapy (Essential Oils)
- Arthritis
- Asthma
- Astragalus
- Atherosclerosis
- Athlete's Foot
- Atkins Diet
- Attention-deficit Hyperactivity Disorder (ADHD)
- Autism or Autistic Spectrum Disorders
- Avocado-soybean unsaponifiables (ASU)
- Ayurvedic Medicine
- B Vitamins
- Back Pain
- Balneotherapy
- Behavioral Approaches or Behavior Change
- Belladonna (MedlinePlus)
- Beta Carotene
- Bilberry
- Bio-identicals
- Biofeedback
- Biotin
- Bipolar Disorder
- Bitter Orange
- Black Cohosh
- Black Tea
- Bladderwrack (MedlinePlus)
- Blessed Thistle (MedlinePlus)
- Blond Psyllium (MedlinePlus)
- Blue-Green Algae (MedlinePlus)
- Blueberry (MedlinePlus)
- Bodybuilding
- Bone Health
- Boron (MedlinePlus)
- Boswellia: See
Ayurvedic Medicine: In Depth - Bowel Disorders
- Brain
- Breathing exercises
- Bromelain (Pineapple Extract)
- Butterbur
- Caffeine
- Calcium
- Calendula (MedlinePlus)
- Cancer
- Cardiovascular Diseases or Heart Disease
- Carnitine
- Carotenoids
- Carpal Tunnel Syndrome
- Cartilage, Bovine or Shark
- Cat's Claw: At a Glance
- Cataract
- Chamomile
- Chasteberry or Vitex
- Chelation for Heart
- Children
- Chinese Herbal Medicine
- Chiropractic
- Cholesterol, High
- Chondroitin
- Chromium (Including Chromium Picolinate)
- Chronic Pain
- Chronic Venous Insufficiency
- Cinnamon
- Circadian Rhythm: See
The Intensity and Duration of Exposure to Light Can Affect the Circadian Rhythm
(05/12/10) - Clinical Trials
- Clove (MedlinePlus)
- Cocoa
- Coenzyme Q10
- Cognitive Decline
- Colds and Flu
- Colic
- Colloidal Silver
- Colon Cleansing
- Concussion: See
Can a Dietary Supplement Treat a Concussion? No! (FDA;
08/25/14
) - Constipation
- Coronary Artery Disease (CAD): See
Chelation for Coronary Heart Disease Information - Cranberry
- Creatine
- Crohn's Disease
- Cupping
- Curcumin
- Dandelion: At a Glance
- Dandruff: See
Tea Tree Oil: At a Glance - Deep Breathing
- Dementia
- Dental Health
- Dental Pain
- Dental Plaque: See
Pomegranate: At a Glance - Depression
- Detoxification or Cleansing
- Devil's Claw
- DHEA
- Diabetes
- Diabetic Retinopathy
- Diarrhea
- Dietary Supplements
- Dimethyl Sulfoxide (DMSO) and Methylsulfonylmethane (MSM)
- Dimethylamylamine (DMAA)
- Dong Quai
- Ear Candling
- Ebola Hemorrhagic Fever
- Echinacea
- Echium Oil
- Eczema
- Edema or Swelling: See
Grape Seed Extract: At a Glance - Electroacupuncture
- Energy Drinks
- Ephedra and Ephedrine Alkaloids or Ma Huang
- Epilepsy
- Erectile Dysfunction (ED)
- Eucalyptus (MedlinePlus)
- European Elder (Elderberry) or Sambucus
- Evaluating Web (Internet) resources
- Evening Primrose Oil
- Eye Conditions
- Falling and Balance
- Fatigue
- Fatty Acids
- Fenugreek
- Feverfew
- Fibromyalgia
- Fish Oil: See Omega-3
- Flaxseed and Flaxseed Oil
- Flu (Influenza)
- Folic Acid (Folate)
- Food Allergies
- Fungal Infections
- Gamma Linolenic Acid
- Gamma-tocopherol
- Garcinia Cambogia: At a Glance
- Garlic
- Gastrointestinal Conditions or Digestive Problems
- Ginger
- Ginkgo biloba
- Ginseng (Asian or North American)
- Glaucoma
- Glucosamine
- Goldenseal
- Gout: See
Public Notification: Ginseng She Lian Wan contains hidden drug ingredients (FDA;
05/04/15
) - Grape Seed Extract
- Grapefruit
- Gray Hair: See
FTC Challenges Marketers’ Baseless Claims That Their Supplements Prevent or Reverse Gray Hair (
05/13/15
) - Green Tea: See Tea
- Guided Imagery
- Hair Loss
- Hatha Yoga
- Hawthorn
- Headache
- Heart Failure
- Heartburn: See
Bitter Orange: At a Glance - Helicobacter pylori (H. pylori) Infection
- Hepatitis C
- Herbal Viagra
- Herbs (Botanicals)
- Herpes
- HIV (Human Immunodeficiency Virus) or AIDS (Acquired Immune Deficiency Syndrome)
- Homeopathy
- Honey
- Hoodia
- Hops: See
NIH awards nearly $35 million to research natural products
(09/09/15) - Hormones
- Horse Chestnut
- Horsetail (MedlinePlus)
- Hospice Care
- Hot Flashes
- Huntington's Disease
- Hyperbaric Oxygen Therapy
- Hypertension (High Blood Pressure)
- Hypertriglyceridemia (High Blood Triglyceride Levels)
- Hypnosis or Self-hypnosis
- Immunosuppression: See
Mouse Study Shows Green Tea Polyphenols May Repair DNA Damage Caused by UV Radiation
(02/01/10) - Impetigo
- In Vitro Fertilization (IVF): See
Acupuncture Shows Promise in Improving Rates of Pregnancy Following IVF
(03/08/08) - Indigestion or Upset Stomach
- Infertility
- Inflammatory Bowel Disease (IBD)
- Insomnia
- Insulin Resistance
- Intermittent Claudication: See
Ginkgo: At a Glance - Iodine
- Iron
- Irritable Bowel Syndrome (IBS)
- Joint Pain…Also see Arthritis
- L-Arginine (MedlinePlus)
- L-Tryptophan
- Labor Pain
- Lactoferrin
- Laetrile (Amygdalin)
- Lavender
- Lemon or Lemon Balm: See
Aromatherapy May Make Good Scents, But Does It Work?
(04/01/08) - Licorice Root or Glycyrrhizin
- Light Therapy
- Liver Disease
- Lobelia
- Low-Back Pain
- Lung or Pulmonary Disease
- Lutein
- Lycium (MedlinePlus)
- Lycopene
- Lyme Disease
- Magnesium
- Magnets
- Malaria
- Manganese
- Marijuana and Cannabinoids
- Massage
- Meditation
- Mediterranean Diet Information (MedlinePlus)
- Megavitamins
- Melatonin
- Men (or Men and Boys or Males)
- Menopause
- Mental Health
- Metabolic Syndrome
- Methylsulfonylmethane (MSM)
- Migraine: See Headaches
- Military and Veterans
- Milk Thistle or Silymarin
- Mind and Body Practices
- Mindfulness
- Mindfulness-Based Stress Reduction (MBSR): See Meditation
- Minerals
- Mistletoe or European Mistletoe
- Monounsaturated Fatty Acids: See
Study Explores Relationship Between Fatty Acids and Cognitive Decline in Women
(05/01/11) - Mouth Ulcers From Cancer Treatment/Chemotherapy/Radiation: See
Chamomile: At a Glance - Moxibustion
- Multiple Sclerosis
- Multivitamins
- Muscle Pain
- Music Therapy
- Nasal Congestion
- Nasal Irrigation or Rinsing
- Nasal or Sinus Swelling: See
Bromelain: At a Glance - Naturopathy
- Nausea or Vomiting
- Neck Pain
- Necrotizing Enterocolitis
- Nerve Pain: See
Public Notification: Asihuri Plus Forte contains hidden drug ingredients (FDA;
05/04/15
) - Neti Pot
- Neurodegenerative Diseases
- Neurofeedback
- Neurologic Conditions
- Niacin (Vitamin B3)
- Night Sweats
- Night Vision: See
Bilberry: At a Glance - Noni (Morinda)
- Obesity
- Omega-3 Fatty Acids
- Omega-6 Fatty Acids
- Opioids
- Orthopaedics: See
Adjuvant Treatment of Distal Radius Fractures With Vitamin C (link is external) (American Academy of Orthopaedic Surgeons) - Osteoarthritis
- Osteopathic Manipulative Treatment
- Osteoporosis
- Ovarian Cyst: See
Polycystic Ovary Syndrome (HHS Office on Womens Health)
- Pain
- Palmitic Acid: See
Laboratory Study Explores Anti-HIV Potential of Palmitic Acid
(12/01/09) - Pantothenic Acid (Vitamin B5) (MedlinePlus)
- Parkinson's Disease
- Passionflower
- Patient-practitioner Relationships
- Pediatrics: Children or Adolescents (Teenagers)
- Pennyroyal (MedlinePlus)
- Peppermint and Peppermint Oil
- Peripheral Arterial (Vascular) Disease
- Phosphate Salts (MedlinePlus)
- Phytoestrogens or Plant Estrogens
- Placebo Effect
- Polycystic Ovary Syndrome
- Polyphenols
- Pomegranate
- Precision Medicine Initiative
- Pregnancy
- Premenstrual Syndrome (PMS)
- Probiotics
- Progressive Relaxation
- Propolis (MedlinePlus)
- Prostate Enlargement (Benign Prostatic Hypertrophy or BPH)
- Psoriasis
- PTSD (Post-traumatic Stress Disorder)
- Pycnogenol
- Red Clover
- Red Yeast Rice
- Reflexology
- Reiki
- Relaxation Techniques
- Researchers
- Respiratory Infections
- Respiratory Problems
- Resveratrol
- Rheumatoid Arthritis: See Arthritis
- Rhodiola: At a Glance
- Riboflavin (Vitamin B2)
- Ringing in the Ears (Tinnitus)
- Ringworm: See
Bitter Orange: At a Glance - Rosacea
- S-Adenosyl-L-methionine (SAMe)
- Safety
- Sage
- Saw Palmetto
- Schisandra: See
Hepatitis C and Dietary Supplements - Seasonal Affective Disorder
- Seasonal Allergies
- Seizure: See
In the News: Component of Marijuana Reduces Seizures in Some Children With Epilepsy - Selenium
- Seniors or Older Adults or Elderly
- Senna (MedlinePlus)
- Sexual Enhancement
- Shingles
- Silver Acetate: See
5 Things To Know About Complementary Health Approaches for Quitting Smoking - Silver, Colloidal
- Silymarin
- Sinus Infections: See
European Elder: At a Glance - Sinus Irrigation or Rinsing
- Skin Conditions
- Sleep Disorders
- Smoking Cessation
- Sore Throat: See
Sage: At a Glance - Soy
- Spinal Manipulation
- Spirituality
- St. John's Wort (Hypericum)
- Stamina or Energy or Athletic Performance
- Statistics
- Steroids and Steroid-like Substances
- Stress
- Stroke
- Sublingual Immunotherapy
- Swedish Massage
- Tai Chi
- Tea
- Tea Tree Oil (Melaleuca Oil)
- Teething
- Temporomandibular Disorder or Bruxation
- Tension Headaches
- Therapeutic Touch
- Thiamin (Vitamin B1)
- Thunder God Vine
- Thymus Extract: See
Hepatitis C and Dietary Supplements - Tinnitus (Ringing in the Ears)
- Traditional Chinese Medicine (TCM)
- Transcendental Meditation
- Travel: See
Complementary Health Approaches for Travelers - Turmeric
- Ulcerative Colitis
- Ulcers, Stomach: See
Cat's Claw: At a Glance - Urinary Symptoms: See
Saw Palmetto: At a Glance - Urinary Tract Infection (UTI)
- Vaccinations/Immunizations for Children
- Valerian
- Vascular Fragility: See
Grape Seed Extract: At a Glance - Vitamin A (Retinol)
- Vitamin B12
- Vitamin B6
- Vitamin C (Ascorbic Acid)
- Vitamin D
- Vitamin E
- Vitamin K
- Vitamins and Minerals
CDC Guideline for Prescribing Opioids for Chronic Pain
Vital Signs: Overdoses of Prescription Opioid Pain Relieversand Other Drugs Among Women - United States, 1999-2010
Evidence-Based Medicine: Literature Reviews
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- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Herb-Drug Interactions (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Herb-Drug Interactions (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Literature on Depression 2 (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Literature on Dietary Supplements and Safety (PubMed®)
- Literature on Dietary Supplements and Safety (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Herb-Drug Interactions (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Herb-Drug Interactions (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Herb-Drug Interactions (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Herb-Drug Interactions (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Herb-Drug Interactions (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Herb-Drug Interactions (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Literature on Placebo Effect (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Herb-Drug Interactions (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Herb-Drug Interactions (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Herb-Drug Interactions (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Herb-Drug Interactions (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Herb-Drug Interactions (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)
- Systematic Reviews/Reviews/Meta-analyses (PubMed®)
- Randomized Controlled Trials (PubMed®)