Evidence Based Practice

1. Evidence Based Practice Introduction for residents

2. Judith Riley, OD drfoureyes@aol.com 918 527 7210

3. The roots of EBP are in Epidemiology. The set up and use of studies to evaluate populations, treatments, testing, and therapies, looking for outcomes, diagnosis and prognosis. • What studies can do this? Experimental and observational. The study used depends upon the information being sought.

4. Experimental vs. Observational Studies Were exposures assigned by investigators? Once this happens the study becomes experimental. If a natural course of the disease is being followed without interference by the investigator, the study is observational.

5. Experimental vs. Observational studies Experimental are useful for clinical knowledge as far as what choice in treatment, what dose, how long to treat. Observational studies lead to knowledge as to the etiology and risk factors for human disease. Who gets disease? What are the risks for morbidity and mortality?

6. Types of Experimental Studies • Non Randomized trial: subjects are knowingly assigned to the control or trial group. This can lead to bias in the findings. • Randomized trial: The subjects are assigned to groups in a masked/blinded fashion: be it single, double blind or triple blind. This leads to less bias in the findings. Not appropriate with toxic or carcinogenic agents, it would be unethical to assign a known carcinogen.

7. Randomized Clinical Trial

8. Use of Randomized trials • New drugs • Non medication treatments of disease • New technology • Screening programs • New ways of organizing care • New delivery services • Randomized clinical trials are for more than just patient care as compared to Randomized trials.

9. Selection of subjects in a random study Should be well documented in writing and direction so others may follow in the future. No element of subjective decision making on the part of the investigator as to whom is included or not. We want to trust the results and be able to repeat them.

10. Masking or Blinding • Once subjects are assigned they should not know which group they are being assigned to. • Placebos may be used to help mask. • The observers or data collectors should not know which group a patient is in or the subject. “Double blinding”. • In a triple blinding; subject, data collectors and data analyzers do not know who is in which group.

11. Crossover • Planned crossover: after being on treatment for a while, the patient is crossed over to the other therapy and observed with it. Each patient acts as their own control. • Carryover from previous therapy must be accounted for. (prostaglandin in gl) Also patient enthusiasm may be better for first treatment. • Unplanned crossover: subjects change treatment during study by subject choice or clinician.

12. Generalizing the results of the study to the general population • Internal validity: study was properly done without major methodologic problems. The study size was good, comparison groups were valid. Findings are valid. • External validity: the new therapy is better for the disease treatment regardless of where the patients are treated, not just for the study group. It can be generalized to the entire population.

13. FDA phases • Phase I; clinical pharmacologic studies of small groups (20-80) looking for toxic and pharmacologic effects. • Phase II; clinical investigations of 100 to 200 patients for efficacy and relative safety. • Phase III; large-scale randomized controlled studies for effectiveness and relative safety which are often multicentered

14. Licensed after passing Phase III • Unfortunately some adverse effects such as carcinogenesis and teratogenesis may not manifest for many years. • Phase IV studies are post marketing surveillance to monitor new agents as they are used for treatment. • Avandia , almost recall this summer.

15. Publication bias • Not all results of clinical studies are published • Erroneous conclusions may be drawn if only one side is published. • Dramatic results are more likely to be published. • Funding may affect what is published. • All clinical trials of medical interventions must be registered in a public trial registry before any participants are enrolled.

16. Review: Contact Lens Spectrum • What makes a trial valid? • Design and Randomization • Control of Variables • Masking • Number and composition of subjects • Good analysis and true representation of results • Meaningful results • Validity to your patient

17. Types of observational study designs • Cohort study: analytical study • Case-control study: analytical study • Cross-sectional study: analytical study • Case study: descriptive study

18. Types of Observational Studies Are groups set up and chosen to be observed? Yes…..this becomes an analytical study as now comparisons are being made between the two groups. No……this becomes a descriptive study and usually is used to develop hypothesis for future studies.

19. Analytical Observational Studies The direction of the study determines the type of study: • If you first look for exposure, and then check the outcome: Cohort Study. This is good to find causal relationships. • If you first look at the outcome and then go back and check for exposure, this is a Case Control study and is good for studying rare diseases. • If you look at the exposure and the outcome at the same time, this is a Cross-Sectional study and you can identify prevalence with it.

20. Cohort study • A group of exposed individuals and a group of nonexposed individuals are identified and followed up on to compare the incidence or rate of death from disease in the two groups. • If a positive association exists between the exposure and the disease, the proportion of the exposed in whom the disease develops should be greater than in the nonexposed group. Great for finding the cause of a disease.

21. Cohort compared to Randomized Studies • Both studies compared exposed and non exposed groups. • Studies with harmful exposures can not be randomized such as carcinogens so cohorts can be used ethically. Lifestyle choices lead to some people having desired exposure for study. • When not performing a randomized study questions are often left unanswered. Are other factors besides the tested exposure leading to conclusions?

22. Cohort Studies

23. Prospective Cohort Study • Also called concurrent cohort or longitudinal study. • A defined population is chosen and then followed over time. First seeing who develops the disease and then what course the disease takes. • This type of study takes many years. • Exposure and nonexposure are found as they occur during the study.

24. Retrospective Cohort Study • Also called historical cohort study or nonconcurrent prospective study. • Use past data and histories to establish data. • Exposed and nonexposed cases are still compared, less time is needed. • Exposure is ascertained from past records and outcome is known when the study begins from existing records.

25. Biases in cohort studies • Bias in assessment of the outcome: observer knows exposure in subjects, biasing outcome. • Information Bias: quality of information should be equal between exposed and nonexposed. Subjects may be the source of information bias. Poor information given. • Biases from nonresponse and losses to follow-up: poor subject response to survey and lost subjects • Analytic Bias: strong preconceptions may lead to bias in interpretation of results.

26. Case-Control Studies • Case studies or case series are a way to observe the course of the disease. • With out a comparison or control group conclusions are not reliable. • Comparison is an essential component of epidemiologic investigation, case-control study design uses comparison. Case studies do not.

27. Design of Case-Control Study

28. Sometimes a Case-Control study is called a backward Cohort as in cohort the exposure is first identified and then the disease. Case-Control first identifies the presence of disease and then the exposure.

29. What case-control is not • This is not a measurement of prevalence. • The number of controls is chosen by the investigator and does not reflect the prevalence of the disease in the population. • It is not a cohort test as the study begins with people with the disease and compares them to people without the disease. Cohort studies work with exposed and non exposed people and follows them for development of disease over time.

30. Case-control studies are valuable when disease is rare. • Cases may be easy to locate from established records. • Case-control studies are usually faster than cohort studies.

31. When to use case-control studies • First step when searching for cause of an adverse health outcome. • Compare people with disease and people without the disease. • Figure out which exposure or characteristic is causing the disease. • Once the relationship is documented, then a more expensive cohort study may be done to explore if exposure is linked to the disease.

32. Cross-sectional studies • The characteristics of a population are studied at one time point, this study can be used to document prevalence. • Exposures, disease and outcomes can all be studied. • Useful for determining health care needs.

33. We have studies, Using the strengths of the different forms of studies, questions about patients can be answered. We can look for population characteristics, treatment options, comparisons and expected outcomes Evidence based practice turns information from studies into clinical decisions and application.

34. Archie Cochrane • MD/ Epidemiologist from Scotland • In 1972 published: ”Effectiveness and Efficiency” bringing attention to the bad effects in health care from lack of available evidence. • “It is surely a great criticism of our profession that we have not organized a critical summary, by specialty or subspecialty, adapted periodically, of all relevant randomized controlled trials”

35. An international systematic review of clinical trials by specialty was his proposal for improving health care. • In the 1980s, Iain Chalmers set about starting the pilot of Effective Care in Pregnancy and Childbirth, the first area of clinical practice reviewing RCT’s. • This review exposed gaps in care between research and clinical practice. This led to belief in the benefits of evidence based practice.

36. Corticosteroids for preterm birth

37. Corticosteroid treatment reduced the odds of babies dying from complications of immaturity by 30 to 50%. But due to lack of the information getting to the doctors, thousands died because the 1972 study was not well known. Meta-analysis of these studies helped the use of steroids become a standard.

38. Clinical Decision Making • What test is the best to explore the condition the patient presents with? • Which treatment would be the most effective? • The practitioner’s knowledge base, skills, attitudes, resources, patient’s expectations and concerns all feed into the decision.

40. Dave Sackett A definition from David Sackett, McMaster University, Ontario , Canada: Evidence Based Medicine: integrating individual clinical expertise with the best available external clinical evidence from systematic research to achieve the best possible patient management.

41. 1990: Sackett’s “Just in Time” learningAn EBM Approach to Education • Evidence cart on ward rounds - 1995 • Looked up 2-3 questions per patient • Took 15-90 seconds to find • Changed about 1/3 decisions • Rounds took longer!

42. Evidence Based Medicine or Evidence Based Practice Using the term Evidence Based Practice is more inclusive of different areas of health care practice. The term practice encompasses more than just physiological, anatomical or biochemical processes found in medicine. Practices covers outcomes of clinical activities that are greater than just medicine.

43. Using Evidence Based Practice • Acknowledge that there are uncertainties in clinical knowledge. Both in self knowledge and in changes to knowledge from new findings. • Use research information to reduce uncertainties. • Know which information found is strong and which is weak. • Determine probabilities of uncertainties.

44. New clinical skills in using EBP 1. Efficient literature searching. 2. Application of formal rules of evidence in evaluating the clinical literature.

45. What skills are currently being used? • Attending journals and conferences • Reading journals • Information from pharmaceutical representatives • Textbooks • Published clinical guidelines • Electronic searching • Small group learning • Talking to other colleagues

46. Finding the best information for the clinical questions you have. Questions arise as patients are evaluated and treated. How many question on average arise? In a study of 103 Iowa GPs, in 2.5 days 1101 questions were generated. 702 questions were pursued for answers in print and from human resources. Less than 2 minutes were spent on finding these answers. Of all these questions, only 2 led to a formal literature search.

47. Information seeking habits Physicians report 2 questions for every 3 patients.Observation shows usually 5 questions for each patient. Only 30% of questions were answered, usually by asking a colleague Textbooks were thought to be too old, lack of time to find answers, and lack of knowledge of where to look were given as reasons for not finding answers.

48. Back to the cart David Sackett in 1998, with his evidence cart reported that with 71 information searches to answer clinical questions, 52% confirmed the management decision, 25% led to a new therapy or treatment plan, 23% corrected a previous plan. S. Crowley in 2003, with CAR study showed that 520 clinical questions when the answers were sought in medical literature 53% confirmed the patient management, 47% the medication, diagnostic, or prognostic information was changed.

49. The Study Data of 145 cases and clinical decisions • 31 could be supported by a randomized controlled trial • 65 were supported by a head to head trial (not a placebo-controlled trial) • 23 were supported by case-control or cohort studies • 4 were supported by case series reports • 22 could not be supported by a literature study

50. Use of Randomized clinical Trials to determine probable clinical outcomes in treating patients. 20,000 trials are published each year. In 2005, 55 new trials published every day. Reading every trial would be impossible, so methods to find the most important trials for the the questions that arise in practice are needed.