The document discusses the use of evidence-based medicine to evaluate complementary and alternative medicine. It begins with background on the importance of staying current with medical literature and using well-formulated clinical questions. It then discusses how to develop background and foreground clinical questions using the PICO framework to identify patients, interventions, comparisons, and outcomes. Several examples of applying PICO to clinical scenarios are provided. The document also reviews types of medical literature and types of clinical studies used in evidence-based evaluations.

1. The Use of Evidence-Based Medicine to Evaluate Complementary / Alternative Medicine Developing the Question Judy Burnham USA Biomedical Library

2. A physician who does not use books and journals, who does not need a library, who does not read one or two of the best weeklies and monthlies, soon sinks to the level of the cross-counter prescriber, and not alone in practice, but in those mercenary feelings and habits that characteristic a trade. William Osler Presidential address to the Maryland State Medical Society, April 1897

3. Reading to stay current vs EBM "The clinical literature is now so big that general physicians who want to keep abreast of the journals relevant to their practices have to examine 19 articles a day, 365 days a year." Davidoff F, Haynes B, Sackett D, Smith R: Evidence based medicine: a new journal to help doctors identify the information they need. BMJ 1995;310:1085-6

4. Complementary/Alternative Medicine and Evidence Based Medicine

5. Developing the Question “ To get the right answer, you must first ask the right question.”

6. Background questions Question root (who, what, where, when, how, why) with a verb Some aspect of the disorder itself Sackett DL et al. Evidence-Based Medicine, 2000 What microbial organisms can cause community-acquired pneumonia?

7. Foreground questions Ask for specific knowledge needed to manage a specific patient with a specific disorder Is St. John’s Wort effective in relieving the symptoms of post-partum depression?

8. Background vs Foreground Experience with Condition Background Foreground

9. 5ways well-formulated questions help Help focus learning time on patients’ clinical needs Help focus learning time on your particular knowledge needs Suggest high yield search strategies Suggest forms that useful answers might take Help communicate clearly with colleague for referral

10. The Well Built Clinical Question - PICO P – Patient or Problem I – Intervention, Prognostic Factor or Exposure C - Comparison O – Outcomes

11. A 19-year-old woman comes home from college with an acute maxillary sinusitis. You just heard about treating this with a shorter 3-day course of antibiotics rather than the usual 10 days of prescribed treatment. You wonder whether you should try the shorter course with the patient.

12. P – Patient or Problem Describe a group of patients similar to the one being treated List most important characteristics What is primary problem or disease? Any significant co-existing problems? Sex? Age? Race? (If relevant) adult with acute maxillary sinusitis

13. I – Intervention, Prognostic Factor or Exposure What is the main intervention, prognostic factor or exposure being considered? Drug therapy? Test? Surgery? Exposure? What factors may influence the prognosis of the patient? Age? Co-existing problems? Drug intervention

14. C - Comparison What is main alternative to compare with the intervention? 2 drugs? 2 tests? Question may not always have a specific comparison Most relevant with a therapy question 3 day course vs 10-day course of trimethoprim-sulfamethoxazole

15. O – Outcomes What can you hope to accomplish, measure, improve or affect? What are you trying to do for the patient? Relieve or eliminate symptoms? Reduce the number of adverse events? Improve function or test scores? Same cure rate with fewer adverse effects and lower costs

16. Structure of Well Built Clinical Question Our Question: In adult with acute maxillary sinusitis , does a 3-day course of trimethoprim-sulfamethoxazole yield the same cure rates as a 10-day course , with fewer adverse effects and costs ? affect [Outcome] or [Comparison, if any] does [Intervention] In patient with [Patient/ Problem]

17. Things to remember No right or wrong answers – the question depends on the information needs of the clinician May not need all of the items in the PICO Sometimes helpful to say question out loud Focus on most important issue for patient

18. Too many questions? What is the most important issue for this patient? What issue should I address first? What question, when answered, will help me most?

19. Mrs. Jones has developed light-headedness on her blood pressure medicine and wants to stop taking them. What would you advise her to do? In 68 year old white woman with essential hypertension, no co-existing illness and no significant past medical history , do the benefits of continuing therapy with hydrochlorthiazide outweigh the inconvenience ? (vs no meds) Our Question: affect [Outcome] or [Comparison, if any] does [Intervention] In patient with [Patient/ Problem]

20. PICOmaker Home Screen Univ of Alberta http://www.library.ualberta.ca/pdazone/pico/

21. PICOmaker Input Screen

24. Types of Questions Diagnosis Prognosis Therapy Etiology

25. Diagnosis Differential Diagnosis – rank possible causes by likelihood, seriousness, treatability Diagnostic Testing – how to select and interpret diagnostic tests to confirm or exclude a diagnosis Precision Accuracy Acceptability Safety Expense Is saliva analysis comparable to blood analysis in the clinical setting?

26. Prognosis How to anticipate the patient’s likely course over time and anticipate any likely complications A 69-year old retired teacher returns for follow-up of congestive heart failure that first presented 1 month before. After you review her progress, she asks you about her prognosis.

27. Therapy How to select treatments that do more good than harm, treatments that are worth the efforts and costs of using them A 19-year-old woman comes home from college with an acute maxillary sinusitis. You just heard about treating this with a shorter 3-day course of antibiotics rather than the usual 10 days of prescribed treatment. You wonder whether you should try the shorter course with with patient.

28. Harm/Etiology Cause of disease or condition Does aromatherapy present any risk to pregnant women?

29. Other types of questions Clinical examination gather and interpret findings from H&P Prevention reduce chance of disease by identifying and modifying risk factors diagnosis by early screening Cost-Analysis Compare cost and consequences of different treatment and tests

30. Considering cost as a factor, which test works best for diagnosis of of Prader-Willi syndrome (PWS) and Angelman syndrome (AS). DNA methylation studies followed by fluorescence in situ hybridization (FISH) for any positive DNA result FISH analysis followed by DNA testing for any negative result, simultaneous DNA testing and FISH analysis.

31. Type of Question: Mrs. Jones has developed light-headedness on her blood pressure medicine and wants to stop taking them. What would you advise her to do? Question: In 68 year old white woman with essential hypertension, no co-existing illness and no significant past medical history, do the benefits of continuing therapy with hydrochlorthiazide outweight the inconvenience? affect [Outcome] or [Comparison, if any] does [Intervention] In patient with [Patient/ Problem]

32. A 45-year old male patient who smokes and has a family history of cardiovascular disease asks you if Vitamin E and carotene will help protect him from developing heart problems. Type of Question: affect [Outcome] or [Comparison, if any] does [Intervention] In patient with [Patient/ Problem]

33. A 58-year-old patient with a history of cardiovascular disease wants to try the Atkins diet and asks for your advice. Type of Question: affect [Outcome] or [Comparison, if any] does [Intervention] In patient with [Patient/ Problem]

34. The Medical Literature Primary – original research Experimental (an intervention is made or variables are manipulated) Randomized Control Trials Controlled trials Observational (no intervention or variables are manipulated) Cohort studies Case-control studies Case reports Secondary – reviews of original research Reviews Meta-analysis Systematic reviews Practice guidelines Decision analysis Consensus reports Editorial, commentary

35. Case Series / Case Reports Reports on treatment, etc. of individual patients

36. Choanal atresia: an unusual serious complication of complementary and alternative medical treatment . Tseng CC . Tsai TL . Chen KT . Lin CZ Archives of Otolaryngology -- Head & Neck Surgery. 129(4):475-7, 2003 Apr. The use of complementary and alternative medicine (CAM) is common among patients with chronic, long-standing nasal disease. Complications resulting from inappropriate CAM practices are sometimes reported, but serious complications such as choanal atresia and stenosis are rare. We report a case of choanal atresia and stenosis due to herbal drug (ie, chemical) cauterization of the nasal cavity in a 39-year-old man. We reviewed the literature on why patients previously given conventional treatment seek alternative therapies. The patient underwent surgical intervention to relieve choanal atresia and stenosis. The postoperative course was unremarkable, and follow-up for 1 year revealed no evidence of restenosis. Choanal atresia and stenosis resulting from CAM treatment are rare. Otolaryngologists should be aware of possible complications occurring in patients receiving such treatments.

37. Case Control Studies Studies in which patients who already have a specific condition are compared with people who do not Rely on medical records and patient recall for data collection

38. Hepatitis C; a retrospective study, literature review, and naturopathic protocol . M illiman WB . Lamson DW . Brignall MS . Alternative Medicine Review. 5(4):355-71, 2000 Aug. The standard medical treatment of hepatitis C infection is only associated with sustained efficacy in a minority of patients. Therefore, the search for other treatments is of utmost importance. Several natural products and their derivatives have demonstrated benefit in the treatment of hepatitis C and other chronic liver conditions. Other herbal and nutritional supplements have mechanisms of action that make them likely to be of benefit. This article presents comprehensive protocol, including diet, lifestyle, and therapeutic interventions. The authors performed a retrospective review of 41 consecutive hepatitis C patients. Of the 14 patients with baseline and follow-up data who had not undergone interferon therapy, seven had a greater than 25-percent reduction in serum alanine aminotransferase (ALT) levels after at least one month on the protocol. For all patients reviewed, the average reduction in ALT was 35 U/L (p=0.026). These data appear to suggest that a conservative approach using diet and lifestyle modification, along with safe and indicated interventions, can be effective in the treatment of hepatitis C. Controlled trials with serial liver biopsy and viral load data are necessary to confirm these preliminary findings.

39. Cohort Studies From a large population, follows patients who have a specific condition or receive a particular treatment over time and compared with another group that has not been affected by the condition or treatment studies

40. Use of complementary and alternative medical therapies in patients with cardiovascular disease . American Heart Journal. 145(5):806-12, 2003 May. METHODS: Interviewers administered telephone questionnaires to 107 patients randomly selected from a stratified cohort of 2487 eligible patients participating in a registry of patients with CVD. RESULTS: The current use of CAM therapies was reported by 64% of the patients surveyed. Nutritional supplements (40%) and megadose vitamins (35%) were the most frequently used preparations. Most CAM therapy users (65%) cited their underlying cardiac condition as the reason for taking such therapy. The most common sources of information about CAM were a friend or relative (43%) or the respondent's usual physician. However, although 80% of respondents claimed that they had discussed their use of CAM therapies with their physician, 58% of respondents taking a potentially toxic cardiovascular medication (digoxin, warfarin, sotalol, or amiodarone) were simultaneously taking an oral supplement. CONCLUSION: The use of CAM therapies was high in the cohort of patients surveyed. Physicians caring for patients with CVD need to inquire about CAM therapy use. Further scientific study should be performed to evaluate the potential benefits and risks of CAM therapies in this patient population.

41. Randomized Controlled Trials Study effect of therapy on real patients Include methodologies that reduce the potential for bias Intervention group vs control group Patients assigned in randomized fashion Blinded or non-blinded studies

42. Treatment of Hypertension with Alternative Therapies (THAT) Study: a randomized clinical trial. Journal of Hypertension. 20(10):2063-8, 2002 Oct. OBJECTIVES: To examine the effect of spinal manipulation on blood pressure. DESIGN: This randomized clinical trial compared the effects of chiropractic spinal manipulation and diet with diet alone for lowering blood pressure in participants with high-normal blood pressure or stage I hypertension. Blood pressure observers were blinded to treatment group. SETTING: The study was conducted at the Berman Center for Clinical and Outcomes Research in Minnesota. Chiropractic treatments were administered by chiropractic physicians within private practice settings. PARTICIPANTS One hundred and forty men and women, aged 25-60 years, with high-normal blood pressure or stage I hypertension, were enrolled. One hundred and twenty-eight participants completed the study. INTERVENTIONS: (i) A dietary intervention program administered by a dietitian or (ii) a dietary intervention program administered by a doctor of chiropractic in conjunction with chiropractic spinal manipulation. The frequency of treatment for both groups was three times per week for 4 weeks, for a total of 12 visits. MAIN OUTCOME MEASURES: The primary outcomes for this study were change from baseline in diastolic and systolic blood pressure…

43. Systematic Review Extensive literature search is conducted in systematic fashion Only uses studies with sound methodology Studies are collected, reviewed, assessed and the results summarized according to predetermined criteria of the review question

44. Common complementary and alternative therapies for yeast vaginitis and bacterial vaginosis: a systematic review. Obstetrical & Gynecological Survey. 58(5):351-8, 2003 May. This article is a systematic review of the literature regarding the most commonly used complementary and alternative medicine (CAM) therapies for yeast vaginitis and bacterial vaginosis. A search was conducted of all published literature on conventional search engines ( PubMed, EMBASE, the Cochrane Registry, CINAHL, LILACS) and alternative medicine databases (Natural Medicines Comprehensive Database, Longwood Herbal Taskforce, and Alternative Medicine Alert ), for all studies of the five most commonly used CAM treatments of vaginitis. Inconsistencies in definition of vaginitis, type of intervention, control groups, and outcomes prevented performance of a meta-analysis, and paucity of high-quality studies made ranking by evidence-based scales unsuitable…

45. Meta-Analysis Examines a group of valid studies on a topic Combines results using accepted statistical methodology to reach a consensus on the overall results

46. The effects of exercise on resting blood pressure in children and adolescents: a meta-analysis of randomized controlled trials. Kelly GA. Kelly KS. Tran ZV. Preventive Cardiology. 6(1):8-16, 2003 Winter. Resting blood pressure in children and adolescents can track into adulthood. The purpose of this study was to use the meta-analytic approach to examine the effects of exercise on resting systolic and diastolic blood pressure in children and adolescents. Twelve randomized, controlled trials representing 16 outcomes in 1,266 subjects met the inclusion criteria. Reductions in blood pressure were approximately 1% and 3% for resting systolic and diastolic blood pressures, respectively. However, random-effects modeling using 5000 bootstrap confidence intervals revealed that neither result was statistically significant (systolic, x-bar (x);+/-SEM=-1+/-2; 95% bootstrap confidence intervals=-2 to 0 mm Hg; diastolic, x+/-SEM=-2+/-1; 95% bootstrap confidence intervals=-3 to 0 mm Hg). The results of this study suggest that short-term exercise does not appear to reduce resting systolic and diastolic blood pressure in children and adolescents. However, a need exists for additional studies, especially in hypertensive children and adolescents.

48. Cost-effectiveness of beer versus red wine for the prevention of symptomatic coronary artery disease. Innes G. CMAJ. 1998 Dec 15;159(12):1463-6. BACKGROUND: Until now, red wine has been the cardioprotective beverage of choice, but the convenience and lack of adverse effects make beer a more cost-effective, safe and widely available choice. A paucity of evidence in support of this led to our study. METHODS: During a 6-month period, 11,780 consecutive patrons at 18 randomly selected urban and community liquor distributors were recruited. Participants were randomly assigned to receive either beer or wine daily for 5 years. Of the 10,078 people who met the inclusion criteria, 5033 were assigned to receive red wine and 5039 to receive beer every day. RESULTS: Effectiveness and adverse effects were equal in the 2 groups. However, costs for beer were substantially lower. INTERPRETATION: In view of its effectiveness, low cost, acceptable adverse-event profile and the fact that it is available in convenient single-dose dispensers, beer should replace red wine as the cardioprotective beverage of choice. Type of study?

49. Ice cream evoked headaches (ICE-H) study: randomised trial of accelerated versus cautious ice cream eating regimen BMJ 2002;325:1445-1446 ( 21 December ) Students at Dalewood Middle School in Hamilton (Canada) in classes 63, 81, 82, 83, 84, and 85 were eligible to participate and were approached by the principal author after permission was received from the school's teachers. The primary outcome measure was the incidence and duration of ice cream headache assessed via self reported questionnaires completed 5-10 minutes after eating the ice cream. All statistical tests were conducted on an intention to treat basis and were two tailed (P<0.05). All 145 students from six classes who were approached provided verbal consent. There were no refusals and no loss to follow up. The table shows the baseline characteristics of the two groups. Twenty (27%) of 73 students in the accelerated eating group reported ice cream headache compared with 9 (13%) of 72 students in the cautious eating group (relative risk 2.2 (95% confidence interval 1.03 to 4.94), number needed to harm 6.71 (3.79 to 200.48)). Of the 29 headaches reported, 17 (59%) lasted for less than 10 seconds. The lifetime prevalence of ice cream headache among the participants was 115/145 (79% (73% to 86%)). Type of study?

50. Translating Lifestyle Intervention to Practice in Obese Patients With Type 2 Diabetes: Improving Control with Activity and Nutrition (ICAN) study. Wolf AM, Conaway MR, Crowther JQ, Hazen KY, L Nadler J, Oneida B, Bovbjerg VE. Diabetes Care. 2004 Jul;27(7):1570-6. OBJECTIVE-To assess the efficacy of a lifestyle intervention program that can be readily translated into clinical practice for obese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS-The study consisted of a 12-month randomized controlled trial of 147 health plan members with type 2 diabetes and obesity (BMI >/=27 kg/m(2)). Participants were randomized to lifestyle case management or usual care. Case management entailed individual and group education, support, and referral by registered dietitians; intervention cost was $350 per person. Individuals treated with usual care received educational material. Both groups received ongoing primary care. Outcomes were difference between groups for change in weight (kilograms), waist circumference (centimeters), HbA(1c), fasting lipid levels, use of prescription medications, and health-related quality of life. RESULTS-Case management resulted in greater weight loss (P < 0.001), reduced waist circumference (P < 0.001), reduced HbA(1c) level (P = 0.02), less use of prescription medications (P = 0.03), and improved health-related quality of life (P < 0.001) compared with usual care. The 12-month group difference in weight loss and waist circumference was 3.0 kg (95% CI -5.4 to -0.6) and -4.2 cm (-6.8 to -1.6). HbA(1c) differences were greatest at 4 months (-0.59%, P = 0.006) but not significant by 12 months (-0.19%, P = 0.45). Participants in the case management group lowered their use of medications, primarily diabetes medications, by 0.8 medications per day more than participants treated with usual care (P = 0.03). In seven of nine quality-of-life domains, the case management group improved compared with usual care (P < 0.05). CONCLUSIONS-Moderate-cost dietitian-led lifestyle case management may improve diverse health indicators among obese patients with type 2 diabetes.

51. Do humorous preoperative teaching strategies work? Schrecengost A . AORN Journal. 74(5):683-9, 2001 Nov. Incorporating humor into preoperative teaching may improve patients' ability to recall pertinent instruction. This article describes a study in which an experimental, two-group, pretest/posttest design was used to determine whether there was a significant difference in the amount of knowledge patients recalled after receiving a teaching booklet either with (i.e., experimental) or without (i.e., control) humor. The sample included 50 patients undergoing open-heart surgery. Results indicate that there was no significant difference (F1, 48 = .07, P > .05) between the groups in the amount of knowledge gained related to postoperative pulmonary exercises. Both groups, however, had a statistically significant increase in the amount of knowledge gained from pretest to posttest (F1, 48 = 39.16, P < .05). Before humorous teaching strategies can be recommended for use in preoperative teaching, further research about the relationship between preoperative instruction, humor, and knowledge retention is necessary. Type of study?

52. Levels of Evidence Level I: obtained from at least one properly controlled randomized trial, considered the gold standard of evidence. Level II-1:derived from controlled trials without randomization. Level II-2: well-designed cohort or case-control studies. Level II-3: includes studies with external control groups or ecological studies. Level III evidence is derived from reports of expert committees, not because it is weaker than levels I or II, but because it is often difficult to ascertain the scientific origin of the committee opinion.

53. Evidence Pyramid Case Series/Case Reports Case Control Studies Cohort Studies Randomized Controlled Trial Systematic Review Meta-analysis Animal Research Work downward until you find the answer

54. Questions of therapy, etiology and prevention which can best be answered by RCT can also be answered by a meta-analysis or systematic review. Economic analysis Cost Prospective, blind comparison to gold standard Clinical Exam RCT > cohort study > case control > case series Prevention Cohort study > case control > case series Prognosis RCT > cohort > case control > case series Etiology / Harm Prospective, blind comparison to gold standard Diagnosis RCT > cohort > case control > case series Therapy Suggested Best Type of Study Type of Question

55. Question: In adult with acute maxillary sinusitis, does a 3-day course of trimethoprim-sulfamethoxazole yield the same cure rates as a 10-day course, with fewer adverse effects and costs? Type of question: Type of study: Therapy RCT>cohort>case control> case series affect [Outcome] or [Comparison, if any] does [Intervention] In patient with [Patient/ Problem]

56. Question: Type of question: Type of study: affect [Outcome] or [Comparison, if any] does [Intervention] In patient with [Patient/ Problem]

57. A 42-year old woman presented at the emergency room of the hospital complaining of muscle pain and tiredness. She was found to have hyperventilation and weakness of four limbs, with muscle power of grade 5 ( )/5. All her symptoms gradually subsided over the next few hours. History revealed she was taking maqianzi', a herbal remedy, for neck pain. Could this herbal supplement have caused her problems? Question: In adult woman, does maqianzi cause muscle pain and tiredness? Type of question: Type of study: Etiology RCT>cohort>case control> case series affect [Outcome] or [Comparison, if any] does [Intervention] In patient with [Patient/ Problem]

58. A mother calls the office because her 3-year-old has diarrhea. A friend has told her that zinc supplements had helped when her child had diarrhea. She asks your advice. Question: In an infant or small child with diarrhea, are zinc supplements useful for therapy. Type of question: Type of study: Therapy RCT>cohort>case control> case series affect [Outcome] or [Comparison, if any] does [Intervention] In patient with [Patient/ Problem]

59. A middle-age male patient has heard that onions and garlic help protective against cancer and cardiovascular disease? He has a family history of cancer and is thinking of taking them to help protect him. Question: In an adult with family history of lung cancer will onions or garlic act as a preventive agent? Type of question: Type of study: Prevention RCT>cohort>case control> case series affect [Outcome] or [Comparison, if any] does [Intervention] In patient with [Patient/ Problem]

60. You have heard that kidney yin deficiency is a valid tool to diagnose postmenopausal women with vasomotor symptoms. You need to find further information on this test. Question: In an postmenopausal woman is kidney yin deficiency as effective as standard tools in diagnosis of vasomotor symptoms? Type of question: Type of study: Diagnosis Prospective blind comparison to gold standard affect [Outcome] or [Comparison, if any] does [Intervention] In patient with [Patient/ Problem]

61. A study suggests that compound coenzyme Q10 can slow disease progression in patients with early-stage Parkinson's disease (PD). Should you recommend this to your patients? Question: In an adult with early stage Parkinson’s disease, will compound coenzyme Q10 slow the progression of the disease? Type of question: Type of study: Prognosis Cohort study>case control> case series affect [Outcome] or [Comparison, if any] does [Intervention] In patient with [Patient/ Problem]

62. GTN ointment has been recommended for the management of patients with severe and/or chronic anal fissure. Would this be a good alternative to sphincterotomy for these patients? Question: In patient with chronic anal fissure, will GTN ointment be as effective as a sphincterotomy in management of the problem? Type of question: Type of study: Therapy RCT>cohort>case control> case series affect [Outcome] or [Comparison, if any] does [Intervention] In patient with [Patient/ Problem]