This is the old version of SRDR. The next, SRDRplus is available! Registration of your SRDRPlus account is free and approval is automatic. Click Here to register an SRDRPlus account.

Advanced Search

Completed Systematic Reviews




Catheter Ablation for Treatment of Atrial Fibrillation [Prospectively Entered]


Public Project Complete

Statistics: 50 Studies, 7 Key Questions, 2 Extraction Forms,
Date Published: Feb 17, 2016 06:14PM
Description: Because catheter ablation is increasingly being used to treat AF patients in the Medicare population, and there is uncertainty regarding the efficacy and harms of this procedure in this population in particular, a systematic review to re-evaluate the current state of evidence, identify and evaluate inconsistencies in the evidence, and identify important research gaps is warranted to help inform clinical practice and policy.
Contributor(s): Andrea Skelly (PhD, MPH/Spectrum Research) Marian McDonagh (PharmD/OHSU) Robin Hashimoto (PhD/Spectrum Research) Gillian Sanders-Schmidler (PhD/Duke) Sana Al-Khatib (MD, MHS/Duke) Rochelle Fu (PhD/OHSU) Elaine Graham (MLS/OHSU) Tracy Dana (MLS/OHSU) Erika Brodt (BS/Spectrum Research) Katie Moran (BS/Spectrum Research) Kathryn Mihalovich (BS/Spectrum Research)
Funding Source: Agency for Healthcare Research and Quality (AHRQ). Prepared by the Pacific Nortwest Evidence-based Practice Center under Contract No. HHSA 290-2012-00014-I. The Technology Assessment is available at: http://www.cms.gov/Medicare/Coverage/DeterminationProce
Methodology Description: Using predefined criteria, randomized trials and observational studies comparing the efficacy, effectiveness, or safety of catheter ablation (radiofrequency or cryoballoon ablation) to medical therapy in patients with atrial fibrillation were included. Analyses were stratified by type of atrial fibrillation and length of followup (>12 months vs. ≤12 months). The quality of included studies was assessed, data were extracted, results were summarized qualitatively and using meta-analysis, and the strength of the evidence was graded for each primary outcome.

Zoom Preview | Show Downloadable Content

Off-Label Use of Atypical Antipsychotics: An Update [Entered Retrospectively]


Public Project Complete

Statistics: 129 Studies, 4 Key Questions, 1 Extraction Form,
Date Published: Dec 08, 2015 12:00PM
Description: Objectives: Antipsychotic medications are approved by the U.S. Food and Drug Administration (FDA) for treatment of schizophrenia, bipolar disorder, and for some drugs, depression. We performed a systematic review on the efficacy and safety of atypical antipsychotic drugs for use in conditions lacking FDA approval. Data Sources: We searched PubMed, Embase, PsycINFO, CINAHL (Cumulative Index to Nursing and Allied Health Literature), Cochrane DARE (Database of Abstracts of Reviews of Effects), and Cochrane CENTRAL (Cochrane Central Register of Controlled Trials) from inception to May 2011. We included only English-language studies. Review Methods: Controlled trials comparing an atypical antipsychotic (risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone, asenapine, iloperidone, paliperidone) to either placebo, another atypical antipsychotic drug, or other pharmacotherapy, for the off-label conditions of anxiety disorder, attention deficit hyperactivity disorder, dementia and severe geriatric agitation, major depressive disorder, eating disorders, insomnia, obsessive compulsive disorder (OCD), post traumatic stress disorder (PTSD), personality disorders, substance abuse, and Tourette’s syndrome were included. Observational studies with sample sizes greater than 1,000 were included to assess rare adverse events. Two investigators conducted independent article review, data abstraction, and study quality assessment. Results: One hundred seventy trials contributed data to the efficacy review. Among the placebocontrolled trials of elderly patients with dementia reporting a total/global outcome score that includes symptoms such as psychosis, mood alterations, and aggression, small but statistically significant effect sizes ranging from 0.12 and 0.20 were observed for aripiprazole, olanzapine, and risperidone. For generalized anxiety disorder, pooled analysis of three large trials showed that quetiapine was associated with a 26 percent greater likelihood of "responding," defined as at least 50 percent improvement on the Hamilton Anxiety Scale, compared with placebo. For obsessive-compulsive disorder, risperidone was associated with a 3.9-fold greater likelihood of "responding," defined as a 25 to 35 percent improvement on the Yale Brown Obsessive Compulsive Scale (YBOCS) compared with placebo. We identified 6 trials on eating disorders, 12 on personality disorder, an existing metaanalysis and 10 trials of risperidone or olanzapine for PTSD, 36 trials for depression of which 7 assessed drugs without an FDA-approved indication, and 33 trials of aripiprazole, olanzapine, quetiapine, or risperidone for treating substance abuse disorders. We identified one small trial (N=13) of atypical antipsychotics for insomnia which was inconclusive. For eating disorder patients specifically, evidence shows that atypicals are do not cause significant weight gain. The level of evidence is mixed regarding personality disorders and moderate for an association of risperidone with improving post-traumatic stress disorder. Evidence does not support efficacy of atypical antipsychotics for substance abuse. In elderly patients, adverse events included an increased risk of death (number needed to harm [NNH]=87), stroke (for risperidone, NNH=53), extrapyramidal symptoms (for olanzapine (NNH=10) and risperidone (NNH=20), and urinary symptoms (NNH= from 16 to 36). In nonelderly adults, adverse events included weight gain (particularly with olanzapine), fatigue, sedation, akithisia (for aripiprazole) and extrapyramidal symptoms. Direct comparisons of different atypical antipsychotics for off-label conditions are rare. Conclusions: Benefits and harms vary among atypical antipsychotics for off-label usage. For symptoms associated with dementia in elderly patients, small but statistically significant benefits were observed for aripiprazole, olanzapine, and risperidone. Quetiapine was associated with benefits in the treatment of generalized anxiety disorder, and risperidone was associated with benefits in the treatment of OCD; however, adverse events were common.
Contributor(s): Margaret Maglione, MPP; Alicia Ruelaz Maher, MD; Jianhui Hu, MPP; Zhen Wang, MS; Roberta Shanman, MLS; Paul G. Shekelle, MD, PhD; Beth Roth, MA; Lara Hilton, MPH; Marika J Suttorp, MS; Brett A Ewing, MS; Aneesa Motala, BA; Tanja Perry, BHM
Funding Source: The Agency for Healthcare Research and Quality (AHRQ)
Methodology Description: We conducted an initial update search on June 1, 2008, as part of a project to determine if Comparative Effectiveness Reviews (CERs) funded by AHRQ needed updating; this search included only the drugs aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone. Regular update searches continued through May 2011. The search for off-label use of the newly approved atypicals (iloperidone, paliperidone and asenapine) included all years available in the electronic databases through May 2011. Searches for utilization data were conducted, as were searches for use for new conditions (anxiety, ADHD, eating disorders, insomnia, and substance abuse). Databases searched include: DARE (Database of Abstracts of Reviews of Effects), Cochrane Database of Systematic Reviews, CENTRAL (Cochrane Central Register of Controlled Trials), PubMed (National Library of Medicine, includes MEDLINE), Embase (biomedical and pharmacological bibliographic database), CINAHL (Cumulative Index to Nursing and Allied Health Literature), and PsycINFO. A summary of detailed search strategies is available in Appendix A. Other sources of literature include clinicaltrials.gov, references of included studies, references of relevant reviews, and personal files from related topic projects. In addition, the AHRQ Effective Health Care Program Scientific Resource Center (SRC) at Oregon Health Sciences University requested unpublished studies from pharmaceutical manufacturers and searched the FDA and Health Canada databases. Two trained researchers reviewed the list of titles resulting from our electronic searches and selected articles to obtain. Each article retrieved was reviewed with a brief screening form (see Appendix B: screener) that collected data on medication, psychiatric condition, study design, population, sample size, and study duration. Only studies on humans were included. Studies that did not report any outcomes of efficacy, effectiveness, safety/adverse events, or utilization patterns were excluded. As single dose or short term trials (less than 6 weeks in length) are common for several of the new uses, we decided, at the TEP’s suggestion, not to limit inclusion by study duration. Clinical trials were used to review efficacy outcomes. In the case that no clinical trials were found for a given condition or drug of interest, we turned to observational studies. All reported side effects and adverse events were abstracted from clinical trials, even if the trial did not report efficacy or effectiveness results. We also included large observational studies of adverse events. Reports of utilization and prescribing patterns were accepted if they discussed use in the United States since 1995. Data were independently abstracted by a health services researcher and a psychiatrist trained in the critical assessment of evidence. The following data were abstracted from included trials: trial name, setting, population characteristics (including sex, age, ethnicity, and diagnosis), eligibility and exclusion criteria, interventions (dose, frequency, and duration), any co-interventions, other allowed medication, comparisons, and results for each outcome.

Zoom Preview | Show Downloadable Content

Imaging Techniques for Treatment Evaluation for Metastatic Breast Cancer [Retrospectively Entered]


Public Project Complete

Statistics: 17 Studies, 1 Key Question, 1 Extraction Form,
Date Published: Sep 09, 2015 09:45PM
Description: The purpose of this technical brief is to understand current utilization of metastatic breast imaging modalities for treatment evaluation in the United States, both in order to summarize the current state of the science and to inform future research on this topic.
Contributor(s): Laura S. Gold, Ph.D. Christoph I. Lee, M.D., M.S.H.S. Beth Devine, Pharm.D., Ph.D. Heidi Nelson, M.D., M.P.H. Roger Chou, M.D. Scott Ramsey, M.D., Ph.D. Sean D. Sullivan, Ph.D.
Funding Source: Prepared by the Pacific Northwest Evidence-based Practice Center under Contract No. HHSA 290-2012-00014-I, Agency for Healthcare Research and Quality. AHRQ Publication No. 14-EHC044-EF, available at: March 2015. www.effectivehealthcare.ahrq.gov/reports/fi
Methodology Description: We worked with Key Informants, including clinicians, patient advocates, representatives from the device manufacturing industry, and a product purchaser. Additionally, we searched gray and published literature from 2003–2013. We qualitatively synthesized the information from the Key Informant interviews and the gray literature. From the published literature, we abstracted data on the types of imaging used to evaluate treatment of metastatic breast cancer.

Zoom Preview | Show Downloadable Content

Psychosocial and Pharmacologic Interventions for Disruptive Behavior in Children and Adolescents


Public Project Complete

Statistics: 97 Studies, 2 Key Questions, 1 Extraction Form,
Date Published: Jul 27, 2015 03:22PM
Description: None Provided
Contributor(s): None Provided
Funding Source: None Provided
Methodology Description: None Provided

Zoom Preview | Show Downloadable Content

Venous Thromboembolism Prophylaxis in Orthopedic Surgery [Entered Retrospectively]


Public Project Complete

Statistics: 149 Studies, 8 Key Questions, 8 Extraction Forms,
Date Published: Jul 23, 2015 02:45PM
Description: Objectives: This is an evidence report prepared by the University of Connecticut/Hartford Hospital Evidence-based Practice Center (EPC) examining the comparative efficacy and safety of prophylaxis for venous thromboembolism in major orthopedic surgery (total hip replacement [THR], total knee replacement [TKR], and hip fracture surgery [HFS]) and other nonmajor orthopedic surgeries (knee arthroscopy, injuries distal to the hip requiring surgery, and elective spine surgery). Data Sources. Medline, the Cochrane Central Register of Controlled Trials, and Scopus from 1980 to May 2011 with no language restrictions; Review Methods: Controlled trials of any size and controlled observational studies with >750 subjects were included in our comparative effectiveness review if they were in patients undergoing one of six a priori defined orthopedic surgeries; provided data on prespecified intermediate, final health, or harms outcomes; defined deep vein thrombosis (DVT) and pulmonary embolism (PE) according to rigorous criteria (where applicable), and included prophylactic products (pharmacologic or mechanical) available in the United States. Using predefined criteria, data on study design, interventions, quality criteria, study population, baseline characteristics, and outcomes were extracted. All of the available data were qualitatively evaluated and where possible, statistically pooled. We used random effects derived relative risks (RR) for most analyses and Peto’s Odds Ratios (OR) in comparisons of rare events both with 95 percent confidence intervals (CIs). I2 was used to detect statistical heterogeneity and Egger’s weighted regression statistics were used to assess for publication bias. The strength of evidence (SOE) and applicability of evidence (AOE) for each outcome was rated as insufficient (I), low (L), moderate (M), or high (H); Results: In major orthopedic surgery (THR, TKR, and HFS, respectively), the incidence of DVT (39 percent, 53 percent, 47 percent), PE (6 percent, 1 percent, 3 percent), major bleeding (1 percent, 3 percent, 8 percent), and minor bleeding (5 percent, 5 percent, not reported) were reported in the placebo/control groups of clinical trials. The SOE and AOE were predominantly low for THR and TKR and was insufficient HFS. In major orthopedic surgery, pharmacologic prophylaxis reduced major venous thromboembolism (VTE) (OR 0.21 [0.05 to 0.95], SOE: L, AOE: L), DVT (RR 0.56 [0.47 to 0.68], SOE: M, AOE: L), and proximal DVT (pDVT) (RR 0.53 [0.39 to 0.74], SOE: H, AOE: L), but increased minor bleeding (RR 1.67 [1.18 to 2.38], SOE: H, AOE: M). Prolonged prophylaxis for >28 days was superior to prophylaxis for 7 to 10 at reducing symptomatic objectively confirmed VTE (RR 0.38 [0.19 to 0.77], SOE: M, AOE: L), PE (OR 0.13 [0.04 to 0.47], SOE: H, AOE: L), DVT (RR 0.37 [0.21 to 0.64], SOE: M, AOE: M), and pDVT (RR 0.29 [0.16 to 0.52], SOE: H, AOE: M) but increased minor bleeding (OR 2.44 [1.41 to 4.20], SOE: H, AOE: M). Using both pharmacologic and mechanical prophylaxis reduced DVT (RR 0.48 [0.32 to 0.72] SOE: M, AOE: M) versus pharmacologic prophylaxis alone. Low molecular weight heparins (LMWHs) reduced PE (OR 0.48 [0.24 to 0.95], SOE: M, AOE: L), DVT (RR 0.80 [0.65 to 0.99], SOE: M, AOE: L), pDVT (RR 0.60 [0.38 to 0.93], SOE: H, AOE: L), major bleeding (OR 0.57 [0.37 to 0.88], SOE: H, AOE: L), and heparin induced thrombocytopenia (OR 0.12 [0.03 to 0.43], SOE: M, AOE: L) versus unfractionated heparin. LMWHs reduced DVT (RR 0.66 [0.55 to 0.79], SOE: L, AOE: M) but increased major bleeding (RR 1.92 [1.27 to 2.91], SOE: H, AOE: M), minor bleeding (RR 1.23 [1.06 to 1.43], SOE: M, AOE: M), and surgical site bleeding (OR 2.63 [1.31 to 5.28], SOE: L, AOE: L) versus vitamin K antagonists. LMWHs increased DVT (RR 1.99 [1.57 to 2.51], SOE: M, AOE: L) and pDVT (OR 2.19 [1.52 to 3.16], SOE: L, AOE: L) but reduced major bleeding (OR 0.65 [0.48 to 0.89], SOE: M, AOE: L) versus factor Xa inhibitors. Antiplatelets increased DVT (1.63 [1.11 to 2.39], SOE: M, AOE: L) versus mechanical prophylaxis. Unfractionated heparin increased DVT (RR 2.31 [1.34 to 4.00], SOE: M, AOE: L) and pDVT (OR 4.74 [2.99 to 7.49], SOE: M, AOE: L) versus direct thrombin inhibitors. Intermittent compression stocking decreased DVT (RR 0.06 [0.01 to 0.41], SOE: L, AOE: L) versus graduated compression stockings. We did not have adequate information to evaluate the role of inferior vena cava filter (IVC) filters or to evaluate the impact of prophylaxis on nonmajor orthopedic surgeries; Conclusions: In major orthopedic surgery, while the risk of developing deep vein thrombosis is highest followed by pulmonary embolism and major bleeding, there are inadequate data to say whether or not deep vein thrombosis causes pulmonary embolism or is an independent predictor of pulmonary embolism. The balance of benefits to harms is favorable for providing prophylaxis to these patients and to extend the period of prophylaxis beyond the standard 7–10 days. The comparative balance of benefits to harms for LMWHs are superior to unfractionated heparin. Other interclass comparisons either could not be made due to lack of data, showed similarities between classes on outcomes, or had offsetting effects where benefits of one class on efficacy was tempered by an increased risk of bleeding. The balance of benefits to harms for combined pharmacologic plus mechanical prophylaxis versus either strategy alone could not be determined. We could not determine the impact of IVC filters on outcomes or the impact of prophylaxis on the nonmajor orthopedic surgeries evaluated.
Contributor(s): Diana M. Sobieraj, PharmD; Craig I. Coleman, PharmD; Vanita Tongbram, MBBS, MPH; Soyon Lee, PharmD; Jennifer Colby, PharmD; Wendy T. Chen, PharmD; Sagar S. Makanji, PharmD; Ajibade Ashaye, MD, MPH; Jeffrey Kluger, MD, FACC; C. Michael White, PharmD, FCP, FCCP
Funding Source: The Agency for Healthcare Research and Quality (AHRQ)
Methodology Description: A systematic literature search of Medline, the Cochrane Central Register of Controlled Trials, and Scopus from 1980 to September 2010 was conducted with no language restrictions. The year 1980 was used as a restriction to reflect contemporary practice. Two separate literature searches were conducted. The first search was used to identify studies that evaluated pharmacologic, mechanical, or inferior vena cava filter methods of thromboprophylaxis in patients undergoing major orthopedic surgery, describe the association between patient, surgical, or postsurgical characteristics and VTE or bleeding, or describe the association between intermediate and final health outcomes to answer KQs 1 through 9. The second search was used to identify studies which evaluate pharmacologic or mechanical methods of thromboprophylaxis in patients undergoing knee arthroscopy, surgical repair of a lower extremity injury distal to the hip, or elective spine surgery to answer KQs 10 and 11. Backward citation tracking was also conducted. A grey literature search of regulatory documents, abstracts, and ongoing clinical trials was conducted by the Scientific Resource Center and reviewed by two independent investigators for inclusion into our literature base by applying the same a priori defined inclusion criteria defined below. The literature searches were updated in May 2011. Two independent investigators assessed studies for inclusion in a parallel manner based on a priori defined criteria. In evaluating all KQs, randomized controlled trials (RCTs) of any size or controlled observational studies (case controlled or cohort studies) enrolling at least 750 patients were included if they explicitly reported the use of imaging studies to confirm VTE events (Doppler ultrasound or venography for DVT and spiral computed tomography [CT] angiography or ventilation/perfusion [V/Q] scan with either Prospective Investigation of Pulmonary Embolism Diagnosis [PIOPED] criteria or high clinical suspicion based on symptoms for PE). Observational studies that enrolled fewer than 750 subjects were excluded because numerous RCTs in this literature base enroll over 500 participants, with the most contemporary trials enrolling over 1,000 participants. Therefore observational studies would need to be of larger size to provide additional valuable information on outcomes of interest and applicability. Additional inclusion criteria were used specific to each KQ and are stated below.

Zoom Preview | Show Downloadable Content