1. Evidence-Based Medicine
It is increasingly difficult for health care professionals to stay current with all the developments with drug therapy and for us to keep up with all other information required in clinical practice. Pharmacists work with other health care professionals to solve and prevent drug therapy problems. The pharmacists also needs the literature to do this effectively. Increasingly, clinicians, like pharmacists, are turning to evidence based medicine to identify the best course of action for each patient. Evidence based medicine helps health care professionals sort out the information and make the best decisions for optimal patient care. These strategies can help any healthcare professional to distinguish reliable and beneficial pharmacotherapy options from those that lack the potential to improve patient care and perhaps that may even be harmful.
Lisa M. Lundquist, PharmD, BCPS

2. Learning Objectives Define evidence-based medicine
Describe the rationale of the basis of making clinical decisions
List the steps involved in making patient-care decisions using evidence-based medicine
Given a clinical question, be able to search for evidence and apply to the clinical question
So far, you have learned about research methods and statistical principles. These last two lectures will help you put it all together. After listening to this lecture, you should be able to define evidence based medicine, describe the rational of the basis of making clinical decisions, list the steps involved I making patient-care decisions using evidence based medicine, and given a clinical question, be able to search for evidence and apply to the clinical question.

3. Evidence-Based Medicine
Definition
The conscientious, explicit, and judicious use of current best evidence in making decisions about the care of the individual patient.
It means integrating individual clinical expertise with the best available external clinical evidence from systematic research.
The most common definition of evidence based medicine is taken from Dr. David Sackett. Evidence based medicine is the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of the individual patient. It means integrating individual clinical expertise with the best available external clinical evidence from systematic research. Evidence based medicine aims to apply the best available evidence gained from the scientific method to medical decision making. It seeks to assess the quality of evidence of the risk and benefits of treatment.

4. Steps in the Process Identify a patient
Formulate an appropriate clinical question
Conduct a literature search
Select the key articles
Critically appraise the articles
Apply the results of the search to your patient
There are six steps in the process of evidence based medicine. First you must identify the patient. Clinical problems arise from the care of patients. Second, you must formulate an appropriate clinical question based on the information that you have on the patient. You are converting information needs into focused questions. Next you must conduct a literature search and select key articles. You are efficiently tracking down the best evidence with which to answer the question about your patient. Fifth, you must critically appraise the evidence for validity and clinical usefulness. You must evaluate the literature and lastly, you must apply the results in clinical practice, specifically for your patient. Evidence based medicine requires new skills of the clinician, including efficient literature searching and the application of formal rules of evidence in evaluating the clinical literature. Evidence based medicine always begins and ends with the patient in mind.

5. Steps in the Process Assess Ask Acquire Appraise Apply Assess Appraise
Another way to think about the approach of evidence based medicine is in a circular or continuous process of assessing, asking, acquiring, appraising, and applying. Once you have identified your patient you can assess or identify the clinical problem of your patient and key issues that exist about your patient. Then ask well built questions that can be answered using evidence based medicine. This is formulating a clinical question. You can acquire knowledge using selected resources and primary literature. Then critically appraise the validity importance and applicability of the evidence that has been retrieved. Lastly, apply that evidence to the clinical situation and the patient.

6. Clinical Decision Making
Clinical Experience
Scientific
Explanation / Evidence
Evidence based medicine is the integration of clinical expertise, patient values, and the best evidence into the decision making process into the patient care. Clinical expertise refers to the clinicians cumulative experience, education, and clinical skills. The patient brings to the counter his or her own personal own unique concerns, expectations, and values. The best evidence is usually found in clinically relevant research that has been conducted using sound methodology. The evidence by itself does not make a decision for you, but it can help support the patient care process. The full integration of these three components into the clinical decision making process enhances the opportunity for optimal clinical outcomes and quality of life. The practice of evidence based medicine is usually triggered by patient encounters which generate questions about the effects of therapy, the utility of diagnostic tests, the prognosis of disease, or the ideology of disorders. In a 2003 study of 520 clinical questions for which answers were sought in the medical literature. 53% of the cases, the literature of evidence based medicine confirmed the therapeutic decision, however in 47% of the cases the literature changed the medication or the course of the therapy.
Patient Values

7. Developing a Clinical Question
Who is the patient?
What is the intervention?
Are any alternatives available?
What is the expected outcome?
As we mentioned, evidence based medicine begins and ends with the patient. The next step in the process is to take the identified problem and construct a question that is relevant to the patient case and is phrased in such a way as to facilitate an answer. This is called developing a well built clinical question. The components of constructing a clinical question are listed. Who is the patient? How would you describe the patient that is similar to yours? What is the most important characteristics of the patient? This may include the primary problem, the disease, or even coexisting medical conditions. Sometimes the gender, age, or ethnicity of a patient might be relevant to the diagnosis or treatment of the disease. What is the intervention? Which main intervention are you considering? What do you want to do for the patient? Prescribe a drug, request a diagnostic test, order a laboratory test? Are there any alternative available. What is the main alternative to compare with the intervention? Are you trying to decide between two drugs, treatment or no treatment? Your clinical question does not always need a specific comparison or alternative. What is the expected outcome? What can you hope to accomplish, measure, or improve for this patient? Are you wanting to treat a medical condition, relieve or eliminate symptoms, minimize the number of adverse effects? So to develop our clinical question, we must answer who is the patient, what is the intervention, and what is the expected outcome?

8. Types of Questions Diagnosis Therapy Prognosis Etiology
The practice of evidence based medicine is a process of life-long self directed problem based learning. In which caring for ones own patient creates the need for clinically important information about diagnosis, effects of therapy, prognosis of diseases, and other clinical and healthcare issues. Instead of routinely reviewing the contents of dozens of journals for interesting articles, evidence based medicine suggests that you target your reading to issues related to specific patient problems. Developing clinical questions and then searching current databases maybe a more productive way of keeping current with the literature. Evidence based medicine has been noted to convert the abstract exercise of reading and appraising the literature into the pragmatic process of using the literature to benefit individual patients while simultaneously expanding the clinicians knowledge base.

9. Levels of Evidence Primary Secondary Tertiary Original research
Compilation and interpretation of original research
Tertiary
Recommendations regarding clinical application of secondary evidence
The practice of evidence abased medicine advocates that clinicians search the published literature to find answers to their clinical questions. There are literally millions of published journal articles and studies available to clinicians. Choosing the best resource is an important decision. There are three levels of evidence. Primary evidence is original research. This is the most current source of evidence and it is the day to day progression of medicine. Secondary evidence is the compilation and interpretation of original research. It often summarizes primary evidence or provides you with an assessment of the original research. Tertiary evidence are recommendations regarding the clinical application of the secondary evidence. This is also known as clinical practice guidelines.

10. Primary Evidence
Randomized controlled trial Observational study Uncontrolled trial Descriptive study Case report
There are many types of clinical research. You have discussed the research methodologies for each of these trial designs. This slide shows the increasing strength of primary evidence. A case report involving one patient is considered the weakest level of evidence. The gold standard for primary literature is the randomized controlled trial which is the strongest level of primary evidence.

11. Meta-analysis Systematic review Opinion of respected authorities
Secondary Evidence
Meta-analysis Systematic review Opinion of respected authorities
We said that secondary evidence is the compilation and interpretation of original research. This includes meta-analysis, systematic reviews and opinions of respected authorities. In a meta-analysis results of previously conducted clinical trials are combined and statistically evaluated. Meta-analysis are designed to provide greater insight into clinical dilemmas than individual clinical trials. The Cochran library grants access to systematic reviews which help summarize the results from a number of studies. The opinion of respected authorities is considered the weakness level of secondary evidence and a meta-analysis is considered the strongest level of secondary evidence.

12. Evidence Pyramid Meta-analyses Systematic reviews RCTs Cohort studies
Case-control studies
Case reports/case series
Animal research/laboratory studies
The evidence pyramid is shown here. As you move up the pyramid the amount of the available literature decreases but it increases in its relevance to its clinical setting. Remember, that randomized controlled trials or RCT’s are the gold standard for literature and are most often where your focus will be for answering clinical questions.

13. Tertiary Evidence Clinical practice guidelines
Level A: Strong recommendation
Level B: Recommendation
Level C: Option/alternative
Level D: Recommendation against
Level I: Insufficient evidence
We stated that tertiary evidence or recommendations regarding the clinical application of literature. Clinical practice guidelines have been defined as systematically developed statements to assist practitioner and patient decisions about appropriate healthcare for specific clinical circumstances. The authors of clinical practice guidelines gather evidence, appraise the evidence, and combine the evidence into a concise, convenient readily useable format for clinicians. Two examples for clinical practice guidelines are the national cholesterol education program adult treatment guidelines which are often abbreviated NACP guidelines for cholesterol management and the joint national committee or JNC guidelines for hypertension management. In guidelines, recommendations for a clinical service or treatment is classified by the balance of risk versus benefit and the level of evidence on which the information is based. Listed are the various levels on which recommendations are classified. Level A is a strong recommendation. There is good scientific evidence that suggests the benefits substantially outweigh the potential risks. Level B, there is fair scientific evidence that suggests the benefits outweigh the risk. This is considered to be a recommendation. Level C, benefits are provided but the balance between benefits and risks are too close for making a general recommendation. So Level C treatment is considered an option. Level D, the risk outweigh the benefits, so this is a recommendation against. Level I, the scientific evidence is lacking of poor quality or conflicting such that risks versus benefit can not be assessed. So Level I is insufficient evidence.

14. Literature Search Search strategy Search engines PubMed, OVID
Cochrane Database
Systematic reviews
Clinical practice guidelines
National Clearinghouse
Once you have formulated a well built clinical question you need to determine a search strategy for literature searching. You must translate a clinical question into a useable strategy. You must select an appropriate database to use for the search. You have learned about these databases in your drug information lectures in your POP course. There are literally millions of published reports, journal articles, correspondence, and studies available to clinicians. Choosing the best search engine and search strategy is an important decision. Large databases such as Medline will give you access to the primary literature. Medline is the most comprehensive resource for health related literature searches and is accessible to everyone through PubMed.

15. Evaluating the Evidence
Were the results of the study valid?
Trial design considerations
Generalizability
Follow-up
Power
What were the results?
Can the results be applied to my patients?
Next we must evaluate or appraise the evidence. This is also called clinical literature evaluation. Some questions for us to consider include were the results of the study valid? Trial design considerations, high quality studies have clearly defined eligibility criteria and have minimal missing data. Analysis of blinding, randomization, patient follow-up, and baseline characteristics of patients must come into play here. Generalizability, studies may only be applicable to narrowly defined patient populations. It may not be generalizable to clinical practice. Follow-up, sufficient time for defined outcomes to occur can influence the study outcomes and the statistical power of a study to detect differences in a treatment and a control arm. Power, this mathematical calculation can determine if the number of patients is sufficient to detect a difference in treatment arms. What were the results? Were practical, clinically important recommendations made? Were the results statistically significant? Were they clinically significant? What is the impact of uncertainty? Can the results be applied to my patients? We must return back to our patient. We must now consider the results in the context of our patient and clinical question. Were the patients studied similarly to my patient? We must also consider cost and compliance here.

16. Exercise
Henry is an active 5 year old boy. His mother brought him in for a check-up because Henry has had a fever and a sore throat for several days.  
You suspect Strep and a throat culture is taken. The standard treatment for Streptococcal pharyngitis is oral penicillin three times a day; however, for Henry and his mother, you are concerned about compliance and the expense of this medication. 
You recall reading that a daily dose of amoxicillin is just as good as penicillin, but costs less. You want to review the literature before you decide on amoxicillin for Henry and possibly changing your standard treatment recommendation and practice.
Lets work through the steps in the process of evidence based medicine. Lets consider this patient situation to help us develop a clinical question. Henry is an active 5 year old boy. His mother brought him in for a check-up because he has had a fever an d sore throat for several days. You suspect Strep and a throat culture is taken. The standard treatment for Streptococcal pharyngitis is oral penicillin three times a day; however, for Henry and his mother, you are concerned about compliance and the expense of this medication. You recall reading that a daily dose of amoxicillin is just as good as penicillin, but costs less. You want to review the literature before you go and decide on amoxicillin for Hendry and possibly changing your standard treatment recommendation and practice.

17. Developing the Clinical Question
What is the best treatment for relieving the symptoms of a sore throat?
In children with strep throat, is amoxicillin as effective as penicillin for relief of symptoms?
Is amoxicillin better than penicillin for young children?
Considering the information we know about our patient. Lets develop a clinical question. There are three choices to consider. A, what is the best treatment for relieving the symptoms of a sore throat? B, In children with strep throat, is amoxicillin as effective as penicillin for relief of symptoms. C, Is amoxicillin better tan penicillin for young children? Choice A does not identify a patient population. This question is to general. We want information on specific drug therapies. Choice B is a well built clinical question. We know our patient population, children with Strep Throat. Our intervention amoxicillin. The comparison, penicillin and the outcome we want to achieve, relief of symptoms. Choice C is also to general. Is amoxicillin better than penicillin for what? We need to identify the illness or condition that is being treated.

18. Search Strategy Search Terms Limits Streptococcus Pharyngitis
Amoxicillin
Penicillin
Limits
Randomized controlled trial
Children 0-18 years
Based on the case of Henry, we must identify our search strategy. Search terms that we might consider are Streptococcus, Pharyngitis, which is the medical term for sore throat. Amoxicillin and Penicillin. Likely we would want to use and between all four search terms to encompass all aspects of our clinical question. We can also limit our search to the gold standard of primary evidence, the randomized control trial and to children since our clinical question is related to Henry, our 5 year old patient.

19. Assignment
Using the search strategy on the previous slide and the PubMed database, identify an article which utilizes evidence-based medicine to answer the clinical question.
Bring the abstract of the article you identify to class tomorrow for discussion.
Here is an assignment for you to complete the process of evidence based medicine and to conduct a literature search and select a key article based on our patient and clinical question that we have developed. Using the search strategy on the previous slide and the PubMed database, identify an article which utilizes evidence based medicine to answer the clinical question. Bring the abstract of your article you identify to class tomorrow for our discussion.