Types of questions. Framing a question: PICO question. 12:00-12:45 Study designs. Exercise

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1 Disclaimer: The contents of this presentation are the views of the author and do not necessarily represent an official position of the European Commission. European Union, 2013 Types of questions. Framing a question: PICO question Jesús López Alcalde Public Health Policy Support Unit Institute for Health and Consumer Protection (JRC-IHCP) GRADE Workshop: Agenda 9:00-10:15 Introduction. Guideline development process and the GRADE approach 10:15-11:00 Types of questions. Framing a question: PICO question. Exercise 11:00-11:15 Coffee 11:15-12:00 Choosing outcomes. Relative importance of outcomes. Exercise 12:00-12:45 Study designs. Exercise 12:45-13:30 Lunch 13:30-14:30 Search of the literature. Exercise 14:30-15:00 Determinants of quality of evidence: What can lower the evidence? (I) 15:00-15:15 Coffee 15:15-17:00 Determinants of quality of evidence: What can lower the evidence? (II) Exercise Joint Research Centre The European Commission s in-house science service 9:00-11:15 Determinants of quality of evidence: What can lower the evidence? (III) Determinants of quality of evidence: What can upgrade evidence? 11:15-11:30 Coffee 11:30-13:00 Going from the evidence to the recommendation. Exercise 13:00-13:45 Lunch 13:45-16:00 Using the Guideline Development Tool (GDT) software. Exercise 2 GRADE Workshop Feedback Ispra and December conclusions 2013 Outline Guideline as a list of questions to answer Guideline as a list of questions to answer Types of questions "[..] knowledge is information in action, information focused in results" Peter F. Drucker Question formulation: the PICO format Exercise Take home message: Guidelines formulate questions which lead to actions 3 GRADE Workshop Ispra December GRADE Workshop Ispra December 2013 Outline Guidelines as lists of questions to answer Types of questions Question formulation: the PICO format Exercise 5 GRADE Workshop Ispra December GRADE Workshop Ispra December

2 Types of questions Exercise: Type of question (Background/Foreground) Background questions Question Type of question Definition: What is Chronic Obstructive Pulmonar Disease (COPD)? What is contact investigation in tuberculosis? Background question Mechanism: What is the mechanism of action of beta-agonists? What is avian influenza? Background question Foreground questions What effect do antivirals have on reducing mortality? Foreground question Recomendation Effects interventions: In patients with COPD, do beta-agonists improve survival? Validity of diagnostic tests Foreground questions lead to action, to recommendations! Is this antiviral safe? What proportion of people who have contact with cases of TB are correctly diagnosed with the Mantoux test? Foreground question Foreground question Recomendation Recomendation 7 GRADE Workshop Ispra December GRADE Workshop Ispra December 2013 Types of question: other clasification How common is the problem? Is this diagnostic test accurate? Magnitud of the problem Diagnosis Exercise: Type of question Question 1. What is the sensitivity and specifity of mammography for screening of breast cancer? Type of question Diagnosis Magnitud of the problem What will happen if we do not add a therapy? Prognosis 2. Do centrally organised screening programmes reduce breast cancer mortality? Diagnosis What are the benefits of this intervention? What are the harms associated to this intervention? Modified from OCEBM Levels of Evidence Working Group*. "The Oxford 2011 Levels of Evidence". Oxford Centre for Evidence-Based Medicine. Screening Other preventive interventions Therapy Common harms Rare harms 3. Does the increase of tobacco taxes reduce lung cancer mortality? 4. Does breast cancer screening based in mamography cause anxiety in women? 5. What are the effects of intercessory prayer as an additional intervention for people with health problems already receiving routine health care? Common harms Prognosis Common harms Rare harms 9 GRADE Workshop Ispra December GRADE Workshop Ispra December 2013 This workshop will focus on recommendations about the effects of interventions A hard moment: select the questions to answer in the guideline GRADE does not provide a formal structure for evaluating the quality of evidence underlying questions of prognosis. "I am rather like a mosquito in a nudist camp; I know what I ought to do, but I don't know where to begin" Stephen Bayne Please, select good questions! 11 GRADE Workshop Ispra December GRADE Workshop Ispra December

3 What is a good question? Please, answer Questions in guidelines There is controversy around the answer There is doubt around the answer Want to confirm the present answer It will determine research in future Will improve care, cost, quality of life should be practice driven should NOT be evidence driven Adapted from 13 GRADE Workshop Ispra December GRADE Workshop Ispra December 2013 Outline Guidelines as list of questions to answer Types of questions Question formulation: the PICO format Exercise Framing a foreground question Example: Should we recommend the use of antiplatelet agents in people with vascular disease? P I POPULATION C O 15 GRADE Workshop Ispra December GRADE Workshop Ispra December 2013 PICO question: the Population Example Question: Should we recommend the use of antiplatelet agents in people with vascular disease? Decide how broadly the patients will be defined A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1997;348:1329e39 Antiplatelet agents differ in effectiveness in those with peripheral vascular disease vs. those with myocardial infarction Options for the population's definition: only patients with myocardial infarction; patients with myocardial infarction and stroke; patients with any vascular disease (cerebro-, cardio-, or peripheral vascular disease), etc. POPULATION: Patients with any vascular disease (cerebro-, cardio-, or peripheral vascular disease). It may be inappropriate 17 GRADE Workshop Ispra December GRADE Workshop Ispra December

4 Please, consider "everyday patients", not "ideal patients" PICO question: the Intervention Question: Should we recommend the use of antiplatelet agents for vascular disease? The panel must decide how broadly the intervention will be defined What proportion of everyday depresive patients would be excluded from antidepressant efficacy trials? Please, suggest options to define the intervention: 66% of everyday depresive patients would be excluded Options to define the intervention: all antiplatelet agents; any dose of an specific antiplatelet, aspirin; a relatively narrow range of doses of aspririn, etc. 19 GRADE Workshop Ispra December GRADE Workshop Ispra December 2013 Example: Should we recommend the use of mozarellaversus parmigiano in pizzas? PICO question: the comparator POPULATION: There may be multiple comparators to an intervention Pizza Specify the comparator explicitly! Mozzarela Mozarella Burrata When multiple agents are involved, guideline developers should specify whether the recommendation is suggesting that all agents are equally recommended or that some agents are recommended over others. Parmigiano Customer's satisfaction Take home message: If different kinds of mozzarella differ in taste, a single estimate across the mozzarelas will not well serve the decision-making needs of customers 21 GRADE Workshop Ispra December GRADE Workshop Ispra December 2013 What kind of comparators can we find? Please, suggest One important comment about Comparators: Doing nothing Placebo (an inactive substance) Test your intervention against something meaningful!!!! Sham intervention (an inactive procedure) Other active intervention The same intervention but with different dose, adminstration route, etc. On the contrary you will do marketing, not research 23 GRADE Workshop Ispra December GRADE Workshop Ispra December

5 Administered twicea day (morning and night) Examples of meaningless comparators Example of meaningless comparison A comparator known to be useless A comparator known to be useful but in the trial is used in a useless way (for example, at a low or high dose) Amitryptiline (new antidepressant) Aparently free of side effects like drowsiness Versus Paroxetine (old antidepressant) Old drug known to make people sleepy "Onethingthat'slikelytomakeyournew treatmentlook goodistestingit against something that doesn't work very well; this might sound absurd, or evencruel [ ]" Normally given by night Ben Goldacre, 2012: Bad Pharma: How Medicine is Broken, and How We Can Fix It Amitryptiline Versus Paroxetine Outcome: daytime sleepiness Safer Nerv Ment Dis 190: , 2002 Ben Goldacre, 2012: Bad Pharma 25 GRADE Workshop Ispra December GRADE Workshop Ispra December 2013 A guideline question often involves another specification: High income environment 27 GRADE Workshop Ispra December 2013 The SETTINGwhere the recommendation is intended Middle income environment Low income environment Should we recommend the use of antibiotics for children with otitis media? Low risk of mastoiditis High risk of mastoiditis Framing a foreground question Example: Should we recommend the use of antiplatelet agents for vascular disease? P I C O 28 GRADE Workshop Ispra December 2013 POPULATION +SETTING Please, consider the context! Take home message: When defining P, I and C The magnitude of the effect on the key outcomes should be similar across the range of patients and interventions considered by the question Evidence of the importance of the context: a dramatic document Consider the context where the recommendation will be applied 30 GRADE Workshop Ispra December

6 Disclaimer: The contents of this presentation are the views of the author and do not necessarily represent an official position of the European Commission. JRC xxxxx European Union, 2013 PICO format in words Any questions? Should [I] versus [C] be used for/in [P]? Exercise 31 GRADE Workshop Ispra December 2013 Exercise: Define Population, Intervention and Comparator (30 min) Background Anticoagulants (blood thinners) may improve the survival of patients with cancer This benefit could be related to the prevention of blood clots and to a direct antitumor effect (in addition to preventing blood clots) PICO question finally imposed! Should parenteral anticoagulants versus placebo or no intervention be used in patients with cancer with no indication for anticoagulation? The "general" question: Should I give blood thinners in patients with cancer? Instructions: Read Section 0: "Background on anticoagulants" (5 min) Population Patients with cancer with no indication for prophylactic anticoagulation (e.g. perioperatively) or for therapeutic anticoagulation (e.g. for the treatment of deep vein thrombosis) Form groups and select someone to report back (3 min) Specify P, I and C of the clinical question (10 min) Report back to the whole group (2 minutes) Question suggested by the facilitator Intervention Parenteral anticoagulants, in particular, unfractionated heparin (UFH), low molecular weight heparin (LMWH), and fondaparinux (synthetic heparin) Comparator Placebo or no intervention Outcome See next session!!! Akl EA, et al. Cochrane Database of Systematic Reviews 2011, Issue 1. Art. No.: CD GRADE Workshop Ispra December GRADE Workshop Ispra December