1.

When considering implementation of a new medical intervention, which one of the following study designs would be placed at the top of the hierarchy of evidence? A) meta-analysis of randomized trials of B-blocker therapy for acute myocardial infarction B) case report of innovative surgical approach C) observational cohort study of asthma patients D) animal model of hemorrhagic shock E) cross-sectional telephone survey of migraine headache patients Feedback: High quality meta-analysis or large multi-center RCT sit at the top of the evidence hierarchy; animal studies and case reports are at the bottom.

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Correct Answer(s): A

2. Determination of whether the results of a study are applicable to your patient population is best described by which one of the following? A) meta-analysis B) external validity C) confidence interval D) prognosis E) internal validity Feedback: external validity refers to the studies generalizability or applicability to populations other than the study population itself. Internal validity refers to the study providing an unbiased estimate of the underlying truth.

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Correct Answer(s): B

3. You are a pediatric pulmonologist at a community hospital in a medium sized Michigan town (population circa 120,000). You sit on the local county health board and attend a meeting where a respiratory therapist who works at your hospitals emergency department (and who has also been instrumental in setting up a new local asthma coalition) is on the agenda. She gives a presentation entitled The excessive burden of childhood asthma in our community. She has obtained emergency department (ED) billing data from your hospital and has information on the 220 ED asthma visits that occurred in children last year. She shows that almost 60% of these visits were from the same 30 children (mean number of asthma visits per child was 4.4 with a range of 2 to 16). She goes on to provide several compelling anecdotes of children and parents she has seen in the ED who were simply clueless (her words not yours) about the management of their asthma. Examples of this include patients who fail to understand the difference between their rescue and long-term controller inhalers, or who fail to heed any of the instructions on their asthma management plan, or who simply come into the ED every time their inhaler runs out. She then explains to the board that there needs to be a program whereby (quote) we educate these people rather than having them come in to the ED all the time. You decide to review the evidence regarding the effectiveness of asthma education programs following an ED visit. All of the following could be components of a well designed EBM Clinical Question (i.e., PIO or PICO) addressing this particular scenario except: A) standard of care B) asthma education C) billing data D) return visits to the ED E) pediatric asthma patients Feedback: A good EBM Clinical Question includes the patient population, intervention, comparison, and outcome (PICO). An example would be, In pediatric patients that present to the Emergency Department (ED) with acute asthma, does an intensive asthma education program decrease return visits compared to standard of care? Answer B is not directly relevant to the clinical nature of the question.

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Correct Answer(s): C

4. Use the PubMed Clinical Queries tool at the PubMed sitehttp://www.ncbi.nlm.nih.gov/pubmed/ (find the Clinical Queries link under PubMed Tools in the centre column). Enter the search terms asthma AND education ANDemergency department. Which one of the following categories would be the most appropriate to click on to start your search? A) etiology B) diagnosis C) clinical prediction guide D) prognosis E) therapy Feedback: This is a question about therapy, which in this case is an asthma education program. The clinical queries tool will automatically enter search terms that are aimed at finding study designs that match issues of therapy.

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Correct Answer(s): E

5. Now perform the above search using the narrow, specific search option under 'Scope' pull down menu box. One of the "top 30 hits" is the article by Brown et al (number 27 of the 91 hits) which we will be using in next weeks RCT exercise. Now click on the "Filter citations..." link that is directly underneath the search results. Examine the pre-defined Clinical Queries search filters used for this particular search. All of the following search terms are listed except: A) therapeutic use B) controlled C) randomized controlled trial D) trial E) randomized Feedback: Feedback: All of following terms were automatically entered into the narrow, specific search option: (randomized controlled trial[Publication Type] OR (randomized[Title/Abstract] AND controlled[Title/Abstract] AND trial[Title/Abstract])). A broad/sensitive search casts a wider net by using additional search terms such as therapeutic use which does not appear in the set of terms used for the specific/narrow search.

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Correct Answer(s): A

6. Using the link below listen to the TED talk given by Epidemiologist Ben Goldacre (yes, it is 15 minutes in length) and answer the following question: http://www.ted.com/talks/ben_goldacre_battling_bad_science.html?utm_source=newsletter_weekly_2011-1004&utm_campaign=newsletter_weekly&utm_medium=email According to the talk by Dr Goldacre the single biggest threat to the accuracy (validity) of medical evidence is: A) The use of placebo controlled groups in pharmaceutical drug trials. B) The selective publication of positive research findings (i.e., Publication bias) in combination with a lack of access to the original trial data. C) The over-exposure of so called scientific experts who have limited or no scientific training. D) The limitations of governmental drug approval process. E) The excessive coverage of medical research findings by the lay press.

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Correct Answer(s): B

Points Awarded Points Missed Percentage

5.00 3.00 62.5%

1. A placebo controlled, concealed, blinded RCT was conducted to test the effectiveness of a new anti-platelet agent for secondary stroke prevention. The therapy is known to reduce the risk of stroke on a relative basis by 20%, however, due to side effects about 30% of patients will stop taking the drug within a few weeks. All of the following are true except: A) The number need to treat to prevent one stroke event cannot be calculated from the information provided B) The results of a per protocol analysis should be similar to the intention to treat analysis C) The intention to treat analysis will underestimate the magnitude of the true treatment effect D) The RRR for the therapy is 20% E) An intention to treat analysis rather than a per protocol analysis should be conducted Feedback: Given that the treatment is known to be effective, then the high non-compliance rate amongst the treated group will mean that the ITT analysis will in all likelihood fail to demonstrate the 20% RRR. Thus answer c is correct. Because of the high non-compliance rate the results of a PP analysis would be very different hence d is incorrect. The NNT cannot be calculated because you have no information on the baseline risk in the population.

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Correct Answer(s): B

2. The RCT is the gold standard of clinical research designs because: A) The RCT can be applied to all clinical questions of interest. B) All of the response options are correct. C) They always include a placebo group. D) Randomization places the control group at a higher baseline risk. E) Randomization reduces confounding from known and unknown confounders. Feedback: Randomization should ensure that there are no differences between the groups at baseline. This phenomenon can be described either in terms of the groups having equivalent prognoses at baseline, or in terms of the control of known and unknown confounding variables (answer B).

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Correct Answer(s): E

3. Which of the following factors could comprise the external validity of a randomized controlled trial: A) Systematic baseline differences between the study and the target populations B) Subjects enrolled were all volunteers C) Differential compliance rates between intervention and control groups D) testing multiple post-hoc sub-group analyses E) a and b

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Correct Answer(s): E

4. The results of an RCT where the event rate in the control subjects was 30% and that in the treatment group was 10% can be described as:

A) RR = 0.5, RRR = 100%, ARR 10%, NNT 50. B) RR = 0.5, RRR = 50%, ARR 10%, NNT 10 C) RR = 2.0, RRR = 50%, ARR 20%, NNT 5. D) RR = 3.0, RRR = 67%, ARR 20%, NNT 20. E) RR = 0.33, RRR = 67%, ARR 20%, NNT 5. Feedback: (RR= TER/CER = 10%/20% = 0.5; RRR = 1 RR; ARR = CER TER = 10%; NNT= 1/ARR = 1/0.1 = 10)

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Correct Answer(s): E

5. Anesthetic death in healthy surgical patients is fortunately very rare, occurring in approximately 1 in 50,000 patients. However, it is estimated that at least half of these deaths occur because of operator error (e.g., overdoes, equipment malfunction) and are thus potentially preventable. As part of a national effort to reduce avoidable in-hospital deaths, a quality improvement project based around implementation of a bedside checklists for all anesthetic procedures is developed. It is proposed to test the efficacy of this checklist by a multi hospital randomized controlled trial involving a total of 500 patients. The principle limitation to doing such a trial would be: A) Unwillingness of anesthesiologists to participate. B) Concern that the drop-out rate would be high. C) Difficulty in blinding the operators/assessors. D) Insufficient power due to low baseline event rate. E) Efficacy of checklist is unproven. Feedback: The question can be answered based on common sense alone. Given the baseline event rate of 1 in 50,000 there is only a 1 in 100 chance that a single anaesthetic death would be observed in the study of 500 subjects. There is absolutely no way of proving anything with a n of 1 sample, hence power is insufficient. For the record, even with a large RRR of 50% formal power analyses indicate that a sample size of over 2 million per group would be required to obtain 80% power.

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Correct Answer(s): D

6. Blinding is an important feature of a RCT because: A) It helps reduce selection bias B) All of the response options are correct C) It helps prevent biased assessment of outcomes D) It is required to do an ITT analysis. E) It helps reduce confounding by indication Feedback: Blinding helps to ensure that outcomes are assessed equally in both groups (that is, it prevents measurement bias) (Answer a). Randomization is what helps reduce confounding and selection bias. An ITT analysis may be performed if the clinical trial is blinded or not.

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Correct Answer(s): C

7.

Based on the table below all of the answers for the missing cells are correct except: A) a = 0.02 B) m = 100 C) c = 0.02 D) f = 0.75 E) k = 0.01

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Correct Answer(s): E

8. Otitis Media with Effusion (OME) is very common in infants and young children. A clinical trial (NEJM 1987;316:432-7) found that in children with three months of OME, resolution rates at 4 weeks were 30% with amoxicillin and only 14% with placebo. What is the relative risk reduction (RRR) of amoxicillin for the resolution of OME? A) 0.19 B) 0.86 C) 2.1 D) 0.70 E) 0.81

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Correct Answer(s): A

1. In a case-control study assessing harm, the most helpful approach to ameliorate the problem of confounding by indication is: A) Collecting data on all relevant prognostic variables B) All other options are correct C) Minimizing recall bias by using memory aids during subject interviews D) Using at least two different methods to verify exposure status E) Ensuring the data collectors are blinded to the hypothesis under investigation Feedback: In a case-control study, correcting for confounding requires adjustment for baseline differences in prognostic variables - typically using multivariable statistical methods. This requires that comprehensive data on baseline prognostic (i.e., confounding) variables be collected - hence the answer is B. Blinding data collectors (option A) would fix a measurement bias not a selection bias. Verifying exposure status (option C) is also only a fix for measurment bias.

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Correct Answer(s): A

2.

As a physician epidemiologist at a very large HMO, you are asked to investigate a possible link that has been reported in the media between a new childhood vaccine given shortly after birth and attention defecit disorder (as reported by a combination of medical record audit and parental interviews) in kindergarten aged children. Considering issues such as timeliness, ethics, feasibility and the quality of evidence generated, which of the following study designs would be the best choice? A) Retrospective cohort. B) Case-control study. C) Multi-state case series. D) RCT. E) Prospective cohort. Feedback: Retrospective cohort is the best design choice, providing an answer that could be obtained relatively quickly. The other potential design option is d (CCS) but is more vulnerable to biases such as selection and other reporting biases (= measurement bias). Prospective cohort would take too long, RCT is probably not ethical or practical, and a case-series is very unlikely to provide any definitive information.

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Correct Answer(s): A

3. What is the number needed to harm for a compound that increases the risk of an adverse event by 3 fold in a population with a 0.3% absolute baseline risk (control event rate)? A) 111 B) 20 C) 167 D) 3 E) 33 Feedback: The rate in the exposed group is 0.9% (i.e., 0.3 x 3), so the absolute risk increase (ARI) is 0.6% (i.e. ,0.9 0.3). The NNH is then 1/0.006 = 166.7

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Correct Answer(s): C

4. The advantages of using a CCS in the study of harm include all the following except: A) CCS can take advantage of matching and restriction to control confounding B) CCS are better than cohort at providing information on the cause of rare diseases. C) CCS can be designed and completed relatively quickly D) All of the other answers are advantages of using CCS E) CCS are better than cohort studies at providing information on the effect of rare exposures. Feedback: The correct answer is C - case-control studies are not very efficient when exposures are rare - in such cases any OR estimate is liable to be extremely impressive because only a handful of cases and controls are exposed. (in such a situation a cohort study that explicitly identified people with the exposure would be a better choice)

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Correct Answer(s): E

5. When new drugs that are thought to have improved safety or efficacy are introduced to the market place they may be preferentially prescribed to specific populations of patients. The tendency to prescribe a specific type of treatment based on a patients underlying prognosis or comorbidity profile is best termed:

A) Channeling B) Cohort Effect C) Confounding bias D) Verification Bias E) Selection Bias Feedback: Channeling bias is the term used to specifically describe this phenomenon (which does result in confounding and can be regarded as a form or selection bias but both of these are the net effects of the phenomenon and not the best term to describe it.

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Correct Answer(s): A

6. The APPROVe Trial was designed as a 3 year placebo controlled double blind RCT to assess the effect of Rofecoxib (a Cox2 inhibitor) in preventing recurrence of neoplastic polyps. As part of the safety monitoring component of the trial, all cardiovascular (CV) events were monitored and independently evaluated by a blinded committee (NEJM 2005;352:10921102). In the placebo group, the rate of significant CV events (defined according to APTC criteria as the combination of death from CV events, nonfatal MI and nonfatal stroke) was 0.54 per 100 patient-years. Rofecoxib increased the risk of significant CV events by 2-fold. What is the number needed to harm (NNH)? A) About 2 B) 185 C) 108 D) 100 E) 54 Feedback: The rate in the rofecoxib group is twice that of the baseline group hence 0.54 x 2 = 1.08 per 100 patient years. Hence absolute risk increase is 1.08- 0.54 = 0.54 or 0.0054. NNH = 1 / 0.0054 = 185.

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Correct Answer(s): B

7. The APPROVe Trial was designed as a 3 year placebo controlled double blind RCT to assess the effect of Rofecoxib (a Cox2 inhibitor) in preventing recurrence of neoplastic polyps. As part of the safety monitoring component of the trial, all cardiovascular (CV) events were monitored and independently evaluated by a blinded committee (NEJM 2005;352:10921102). In the placebo group, the rate of significant CV events (defined according to APTC criteria as the combination of death from CV events, nonfatal MI and nonfatal stroke) was 0.54 per 100 patient-years. Rofecoxib increased the risk of significant CV events by 2-fold. If 100 patients were treated with Rofecoxib for one year, about how many CV events (as defined by APTC criteria) would you expect to see? A) About 2 B) About 20 C) About 0.54 D) About 1 E) Cannot be calculated from the data given Feedback: The rate in the rofecoxib group is twice that of the baseline group hence 0.54 x 2 = 1.08 per 100 patient years. So about 1.

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Correct Answer(s): D