Course: Research in Biomedicine and Health III Seminar 2: Asking a question

 EBM steps ◦ Step 1: Formulating questions that can be answered ◦ Step 2: Finding best evidence ◦ Step 3: Quick critical assessment of the evidence ◦ Step 4: Applying evidence ◦ Step 5: Assessing effectiveness and efficiency of the process

“PICOT” model: Patient (For which patient, population or problem you need information?) Intervention/indicator (What is the intervention you are studying?) Comparison/control (Which is the alternative treatment?) Outcome (What is the effect of the intervention?) Type of study (Which is the optimal study design ?) Who is treated? What is given as a treatment? What is the comparison? What outcome is of interest to us? How to ask a clinical question? What is the study design?

Question typeIdeal study design TherapyRCT PreventionRCT > Cohort> Case-control DiagnosisProspective, blind, randomized trial of comparison with golden standard PrognosisCohort> Case-control> Case series/ Case report Cost and efficiencyEconomic analysis PhenomenonQualitative study

Be precise! Kew words for database search P Patient, problem I intervention C Comparison (not always) O Outcome T Type of study

Aim of steps 1. i 2. : find “pearls”

Examples of clinical questions What is causing migraine? How often a 40 year-old women needs to go to mammography? What is the efficacy and safety of early and long-term use of clopidogrel and aspirin compared to aspirin alone in patients with acute coronary syndrome without ST-segment increase? In patients with mechanical ventilation longer than 48 hours, is oral decontamination with chlorchexidine (CHX) or CHX + colistine useful in decreasing the risk of pneumonia related to ventilation?

Examples of clinical questions Ethiology and risk factors What is causing the problem? Prevalence How common is the problem? Has this patient a problem? Diagnosis Who will have a problem? Prognosis and prediction Intervention How to treat a disease or condition? What is the problem? Phenomenon

 Interventions cover a wide spectrum of activities - from medications and other clinical therapeutics to change in life habits (exercise, smoking cessation) and social activities (education programmes).  Interventions may include patient care for a single patient but also public health activities.

28 year-old man suffers from furunculosis in the last 8 months. These episodes are treated by drainage and 2 different atibiotics, but the disease relapses. The patient asks if the relapses can be prevented. Patient with recurring furunculosis Prophylactic antibiotics No treatment Decrease in relapse of furunculosis Q: In patients with recurring furunculosis, can prophylactic antibiotic therapy in comparison to no treatment decrease the incidence of recurring episodes?

 Reading a medical journal, you find an article about imiquimode cream for the treament of basal cell carcinoma. The notion of a cream as cancer therapy sounds surprising, so you wonder about its efficacy, especially in regard to long- term cure rate. Patient with basal cell carcinoma Imiquimode cream Active placebo – standard/gold therapy Increase in long-term cure rate with the cream Q: In patients with basal cell carcinoma, can im iquimode cream, in comparison to standad surgical intervention, increase the long-term cure rate in these patients?

 Questions about ethiology and risk factors are questions about what causes a disease or health condition.  Harmful outcomes of activities or exposures  Common in public health: ◦ Can intake of certain food increase risk of cardiovascular disease? ◦ Can exposure to infrared waves increase risk of cancer?

Jane is expecting her first baby in two months. She read about the benefits and harms of injections of vitamin K to newborns. She is scared by the reports of increased risk of childhood leukemia in babies administered vit. K injections. She asks you if this is true and what the risk is for her baby. Newborn Vitamin K injection No vitamin K injection Childhood leukemia Q: In newborns, does the administration of vit. K injection increase the risk of childhood leukemia?

 Questions about how many people have a diseases or health condition.  Examples: ◦ What is the prevalence of hearing problems in newborns? ◦ What is the prevalence of Alzheimer’s disease in the population older than 70?

Maria is a 6-month baby coming to her regular check up. She was born prematurely, at the gestational age of 35 months. You want to warn the parents about the odds that Maria may have hearing problems. Infant Premature birth Term birth Deafness Q: In preterm infants, in comparison to term babies, what is the prevalence of deafness?

 Questions about: ◦ How accurate are diagnostic tests in different patient groups. ◦ How accurate are diagnostic tests in comparison to other tests.

Clara is pregnant for the second time. She had her first baby when she was 30 and had amniocentesis to exclude Down’s syndrome. The test was negative, but she was not satisfied because she got results in the 18th pregnancy week. She is now 35 and asks if there is a test with a quicker answer. Your hospital has biochemical test of serum markers and ultrasound of nuchal folds in the first trimester, but you want the check if the test is sensitive and specific enough in comparison to amniocentesis. Pregnant women Serum markers biochemistry + US of nuchal folds Amniocentesis Correct diagnosis (specificity and sensitivity) of Down’s syndrome Q: In pregnant women, is nuchal fold US + serum markers test equaly correct as amniocentesis in diagnosing Down’s syndrome?

 What are the odds for an outcome for a population with certain characteristics (risk factors)? ◦ What are the odds that a man who feels atypical chest pain develops heart failure? ◦ What is predicted mortality and morbidity for a person who is diagnosed with colon cancer?

Clonic seizures in childhood are common and disturbing for parents, but the decision to start prophylactic therapy after the first attack is difficult. To help parents make a decision, you have to explain them the risk of new attacks after the first clonic seizure of undetermined cause. Children A clonic attack of undetermined cause No attack Future attacks Q: In children with a single clonic attack of undetermined origin, in comparison to children without attacks, what is the risk of future clonic seizures?

For each type of clinical question there are study designs that provide best evidence for the question. These are always study designs that have a maximum decrease in bias.

Question typeIdeal study design TherapyRCT PreventionRCT > Cohort> Case-control DiagnosisProspective, blind, randomized trial of comparison with golden standard PrognosisCohort> Case-control> Case series/ Case report Cost and efficiencyEconomic analysis PhenomenonQualitative study

Observational Design Experimental No controlCohort Case- control Non-randomized control Randomized control Open Single blind Double blind Increasing validity of evidence for conclusions on cause and consequence

Examples of disbalance between surogate and relevant outcomes: Disease or conditionSurogate outcomeRelevant outcome Lidocaine for arrythmia after AMI Decreases arrythmiaIncreases mortality Vitamin E for heart disease Decreases the level of free radicals Do not decrease mortality Clofibrate for hyperlipidemia Decreases blood lipid levels Do not decrease mortality Sodium floride for bone fracture prevention Increases bone densitiyDo not decrease fracture rate Hormone replacement therapy Decreases LDL, increasese HDL Do not decrease mortality, can increase incidence of cardiovascular events in women over 60