EVIDENCE DETECTIVES December 28, 2005 Edward Amores, M.D. Reviewed and edited by P. Wyer, M.D. Part I Question Formulation

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1 EVIDENCE DETECTIVES December 28, 2005 Edward Amores, M.D. Reviewed and edited by P. Wyer, M.D. Part I Question Formulation Clinical Scenario Quite often in the Pediatric ED and at times in the adult ED we see acute otitis media, and standard clinical practice is to treat with antibiotics, e.g. amoxicillin. Some attendings advocate the use of a decongestant, e.g. Afrin spray or Sudafed tabs, for decongestion early in the treatment of otitis, with the thought that a decongestant, or for that matter an antihistamine, allows a decrease in the inflammation of the Eustachian tube, so that drainage from the middle ear is more effective. I wanted to examine the evidence behind this practice. We polled the residents at the outset of the session and confirmed that these agents are frequently prescribed along with antibiotics for the treatment of patients with otitis media in the pediatric ED. PICO PICO defines the question, not just generation of search terms. P: Patients who present to the peds emergency dept with symptomatic otitis x 0-3 days/ otoscopic evidence of otitis media without perforation, with or without prior otitis hx I: antihistamines and/or decongestants C: usual co-intervention is antibiotics O: quicker pain relief, decreased incidence of complications, e.g. perf, hearing loss, mastoiditis, return visits Question Do patients presenting to the peds ED with ear complaints/ otoscopic evidence of nonperforated otitis media treated with decongestants/antihistamines in addition to abx note a decrease in duration of symptoms/ incidence of complications/ return visits compared to patients treated with abx alone? Group Search Strategies We divided ourselves into three groups, and asked each group to commit to a search strategy on paper. One group searched Ovid Medline, another Cochrane Database of Systematic Reviews, and the third used Pubmed clinical queries. In preparation for the session I also utilized Google Scholar, and Ovid All EBM Reviews: In Ovid Medline, we entered otitis media AND decongestants OR antihistamines; got 136 hits, mostly old data/studies from the 80's- most were secondary articles, findings also crossed into reviews of chronic OM. Nevertheless, we found our target paper-

2 Cochrane Ear, Nose and Throat Disorders Group Cochrane Database of Systematic Reviews. 4, EBM Reviews - Cochrane Database of Systematic Reviews Flynn, CA. Griffin, GH. Schultz, JK. Decongestants and antihistamines for acute otitis media in children. [Systematic Review] Cochrane Acute Respiratory Infections Group Cochrane Database of Systematic Reviews. 4, In Cochrane s Database of Systematic Reviews, we entered otitis media and got the target paper immediately as the second hit. In Pubmed clinical queries, we entered otitis media AND antihistamines OR decongestants, got 74 hits under systematic reviews, but this included unrelated topics such as treatment for overactive bladder, so I tried narrow, specific search in therapy and got 560 hits. * The teaching point here again, if too many relevant hits, look for a systematic review. Ovid s All EBM reviews, yielded 46 hits with the terms otitis media AND decongestants OR antihistamines. In addition to the target paper, I noted a protocol of interest, entitled Antihistamines and/or decongestants for hearing loss, otalgia or late sequelae associated with otitis media with effusion (OME) in children. Cochrane protocols are reviews that have not yet been completed and hence are not ready to be appraised. Diana s Comments We then invited our research librarian, Ms. Diana Delgado, to comment on the research strategies used. She provided feedback and gave useful pointers on optimizing search strategies. She educated us on different search terms, and on which databases were most useful for specific types of searches. Teaching Points We then reviewed several key teaching points. The following is a sample of some of these points:! A systematic review, such as a Cochrane review, is a higher level of evidence than an individual trial.! A rigorously done search and review demonstrating lack of efficacy of a commonly administered therapy is potentially of high impact that could importantly change practice.! Did the Cochrane review for our target paper pool the results of the individual studies they included for the outcomes we are interested in? If yes, then we definitely need to look at the review as the primary piece of evidence. If not, was it because of differences in how the studies were done or in what they found? If the former, we may need to choose the studies that come closest to the question we have asked and look at them individually.! If a lot of individual studies are found, this clues you in that a systematic review may exist and would be much more efficient than looking through the individual studies yourself and trying to come to a conclusion.! With a Cochrane review, one can easily find the studies they included and excluded.

3 ! One study, particularly if large, may be of particularly high quality and by looking at it in depth we may get a better idea of the quality of research underlying the evidence.! One study may particularly correspond to the population, interventions or outcomes we are interested in. Part II- Critical Review Citation: Flynn CA, Griffin GH, Schultz JK. Decongestants and antihistamines for acute otitis media in children. The Cochrane Database of Systematic Reviews 2004, Issue 3. Most recently substantively updated May 2004

4 Guide I) Are the results valid? Comments 1. Did the review explicitly address a sensible question? Yes, the question asked is plausible- at least intuitively, decongestion of the Eustachian tubes might allow for decreased inflammation and thus more effective drainage of an otitis media. Although 2 classes of medication, antihistamine and decongestants, were included, they were considered separately in the analysis, avoiding possible erroneous pooling of results. 2. Was the search for relevant studies detailed and exhaustive? Yes, the Cochrane search strategy is exhaustive, includes multiple search strategies done by the relevant Review Group and is well documented. 3. Were the primary studies of high methodological quality? The authors used the *Jadad scale scores, a scale used to roughly measure study design quality, and considered concealment of randomization for each study. All the studies were RCT, with 2 reviewers in complete agreement. The studies varid in methodological quality by all measures used and the authors considered whether the weaker studies reported different results from the stronger studies. *See below for explanation of Jadad scores. 4. Were the assessments of the included studies reproducible? Yes, although one should know that Cochrane uses a standard protocol in which the method of assessment is explained.

5 II) What are the Results? 1. What are the overall results of the study? Combination therapy showed a statistically significant decrease in acute otitis media at 2 weeks (RR 0.82, 95% CI 0.68, 0.99); however, there was no significant difference when the weaker studies were removed (RR 1.01, 95% CI 0.94, 1.22). Furthermore, monotherapy showed no significant decrease AOM two weeks later. 2. How precise are the results? Not very precise, as evidenced by the wide Confidence Interval. E.g., for combined therapy for the outcome of persistent otitis at 2 weeks, even when the weaker studies are included, the confidence interval 0.68, 0.99 around the relative risk includes clinically insignificant values. That is, if the RR were 0.99, the relative risk reduction would be 1%. Only 23% (251/1096) of the placebo group had persistent otitis. A reduction of this risk by 1% would yield an absolute risk reduction of only 0.2% and would result in a Number Needed to Treat of 100/0.2 = 500. Few practitioners would be willing to write 500 prescriptions for antihistamines plus decongestants to prevent one child from having otitis 2 weeks later. 3. Were the results similar from study to study? Yes, as evidenced by the p value of heterogeneity- the larger the p value of heterogeneity, the more consistent the studies. When these were removed, reveals no significant change - see slides and response to question 1 above. III) Will the results help me in caring for my patients? 1. How can I best interpret the results to There is no appreciable benefit of using decongestants and /or apply them to the care of my patients? antihistamines in pediatric patients with otitis media. 2. Were all patient-important outcomes considered? 3. Are the benefits worth the costs and potential risks? No repeat visits should have been taken into account. No- there is a risk of toxicity with decongestants and /or antihistamine use in these patients. Summary Our findings are that there is no evidence supporting the use of decongestants and /or antihistamines in pediatric patients with otitis media. In fact, it may prove dangerous given the risk of toxicity. This exercise has allowed us to examine a clinical scenario, to formulate a question using the PICO format, and to review the available evidence- all of

6 which may affect our daily clinical practice. Hopefully, this will translate into improved strategies for searching for evidence in the future. Jadad Scores From A numerical score between 0-5 is assigned as a rough measure of study design/reporting quality (0 being weakest and 5 being strongest). This number is based on a wellestablished, validated scale developed by Jadad et al. (Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Controlled Clinical Trials 1996; 17[1]: 1-12). This calculation does not account for all study elements that may be used to assess quality. A Jadad score is calculated using the seven items in the table below. The first five items are indications of good quality, and each counts as one point towards an overall quality score. The final two items indicate poor quality, and a point is subtracted for each if its criteria are met. The range of possible scores is 0 to 5. Jadad Score Calculation Item Was the study described as randomized (this includes words such as randomly, random, and randomization)? Was the method used to generate the sequence of randomization described and appropriate (table of random numbers, computer-generated, etc)? Score Was the study described as double blind? 0/1 Was the method of double blinding described and appropriate (identical placebo, active placebo, dummy, etc)? Was there a description of withdrawals and dropouts? 0/1 Deduct one point if the method used to generate the sequence of randomization was described and it was inappropriate (patients were allocated alternately, or according to date of birth, hospital number, etc). Deduct one point if the study was described as double blind but the method of blinding was inappropriate (e.g., comparison of tablet vs. injection with no double dummy). 0/1 0/1 0/1 0/-1 0/-1

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8 Jadad >3

9 Concealment A