Evidence Based Medicine From Clinical trials to Clinical Practice Mohamed Meshref M.D, DES( Lyon) Faculty of Medicine Cairo University
EBM: Topics to discuss Introduction to EBM Levels of evidence The process of EBM: Step I: Formulate the clinical question Step II: Finding the evidence (The literature search) Step III: Evaluate the evidence Conclusion
What is EBM? Evidence based medicine is the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients. The practice of evidence based medicine means integrating individual clinical expertise with the best available external clinical evidence from systematic research.
What is evidence-based medicine? Evidence-based medicine (EBM) Patient Values Clinical expertise Best Research Evidence
What is evidence-based medicine? By Best Research Evidence we mean clinically relevant research, often from the basic sciences of medicine, but especially from patient centered clinical research.
What is evidence-based medicine? By Clinical Expertise: we mean the ability to use our clinical skills and past experience to rapidly identify each patient s unique health state and diagnosis, their individual risks and benefits of potential interventions, and their personal values and expectations.
What is evidence-based medicine? By Patient Values we mean the unique preferences, concerns and expectations each patient brings to a clinical encounter and which must be integrated into clinical decisions if they are to serve the patient
What is evidence-based medicine? EBM takes systematic approach to looking at medical evidence. It requires the physician to: Assess your patient Ask Clinical Questions Acquire the best Evidence Appraise the evidence Apply the evidence to patient care
EBM: Topics to discuss Introduction to EBM Levels of evidence The process of EBM: Step I: Formulate the clinical question Step II: Finding the evidence (The literature search) Step III: Evaluate the evidence Conclusion
Evidence Based Medicine Levels - Level I: Adequately powered, high quality randomized trial, or meta-analysis of randomized trials showing statistically consistent results - Level II: Randomized trials inadequately powered, possibly biased, or showing statistically inconsistent results
Evidence Based Medicine Levels - Level III: Non-randomized studies with concurrent controls - Level IV: Non-randomized studies with historical controls (i.e. typical single-arm phase II studies) - Level V: Expert committee review, case reports, retrospective studies
Evidence Based Medicine Meta-Analysis of Phase III Trials/ Systematic reviews Randomized Phase III Trial Phase II Clinical Trial (s) Phase I Clinical Trial (s) In Vitro/Vivo Data Anecdotes
EBM: Topics to discuss Introduction to EBM Levels of evidence The process of EBM: Step I: Formulate the clinical question Step II: Finding the evidence (The literature search) Step III: Evaluate the evidence Conclusion
Step I: Formulating the clinical question Start with the patient: a clinical problem/ question arises out of the care of the patient. The Question: Construct a well-built question derived from the case.
Step I: Formulating the clinical question Anatomy of a good clinical question (PICO) 1. Patient or problem How would you describe a group of patients similar to yours? What are the most important characteristics of the patient? (This may include the primary problem, disease, or co-existing conditions. Sometimes the sex, age or race of a patient might be relevant to the diagnosis or treatment of a disease). 2. Intervention, prognostic factor, or exposure Which main intervention, prognostic factor, or exposure are you considering? What do you want to do for the patient? Prescribe a drug? Order a test? Order surgery? 3. Comparison What is the main alternative to compare with the intervention? Are you trying to decide between two drugs, a drug and no medication or placebo, or two diagnostic tests? 4. Outcomes What can you hope to accomplish, measure, improve or affect? (What are you trying to do for the patient? Relieve or eliminate the symptoms? Reduce the number of adverse events? Improve function or test scores? )
Step I: Formulating the clinical question Clinical Case: Mr. Hussein is a 70 years old male who was diagnosed to have a stage IV NSCLC 8 months ago and was treated with platinum doublet for 4 cycles. He tolerated first line chemotherapy with difficulty. Now he relapsed, his ECOG PS is 1, he is symptomatic, he has no co morbidities. He wants to be treated but doesn t want to suffer from the side effects of treatment as he lives alone. What would be the right question to ask?
Step I: Formulating the clinical question Problem Relapsed NSCLC, elderly Intervention Chemotherapy Comparison (if any) Chemo type, TKIs? Outcome Primary : reduce symptoms, improve survival Secondry: Reduce toxicity Our question may be: For elderly patients with relapsed NSCLC what is the most effective therapy with least toxicity? Key words : NSCLC, second line, chemotherapy, TKI
EBM: Topics to discuss Introduction to EBM Levels of evidence The process of EBM: Step I: Formulate the clinical question Step II: Finding the evidence (The literature search) Step III: Evaluate the evidence Conclusion
Secondary Sources A secondary research is an attempt to synthesize the results and conclusions of two or more publications on a given topic Can I trust this secondary source: (Only if you say yes to the following) No conflict of interest Clearly states the question it addresses There is a clear evidence based methodology behind finding, producing and checking the information The source is reviewed and updated regularly
Useful resources
Is a review addressing a specific research question using explicit methodology of collecting, selecting and appraising studies Systematic reviews
Primary Sources Needed when there is no collective secondary source data Search strategies for MEDLINE are Thesaurus and text word search We might need to do the search using the 2 methods so as not to miss important articles which might have been indexed in a different way.
EBM: Topics to discuss Introduction to EBM Levels of evidence The process of EBM: Step I: Formulate the clinical question Step II: Finding the evidence (The literature search) Step III: Evaluate the evidence Conclusion
Evaluate the evidence Appraise the evidence for: Its validity ( closeness to the truth) Applicability ( usefulness in clinical practice)
Are the results of this therapy study valid? 1. Was the assignment of patients to treatment randomized? 2. Were all the patients who entered the trial properly accounted for at its conclusion? Was follow-up complete? 3.Were patients analyzed in the groups to which they were (originally) randomized? 4. Were the groups similar at the start of the trial? 5. Aside from the experimental intervention, were the groups treated equally?
Are the results applicable to your patient?
EBM: Topics to discuss Introduction to EBM Levels of evidence The process of EBM: Step I: Formulate the clinical question Step II: Finding the evidence (The literature search) Step III: Evaluate the evidence Conclusion
Conclusion
Conclusion Remember that: Prestigious journals and authors are never a seal of guarantee of quality Research needs to be filtered Research of poor methodology harms our practice and need to excluded Controversial results of studies needs to be summarized
Conclusion Because randomized trials and systematic review of randomized trials is much more likely to inform us and much more likely to mislead us, it has become the gold standard for judging whether a treatment does more good than harm. However, some questions about therapy do not require randomized trials or cannot wait for the trials to be conducted. And if no randomized trials have been carried out, we must follow the trail to the next best external evidence and work from there David L Sackett BMJ 1996