Tammeka Swinson Evans

Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Depression: A Systematic Review and Meta-Analysis

OBJECTIVE To evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) in patients with major depressive disorder (MDD) and 2 or more prior antidepressant treatment failures (often referred to as treatment-resistant depression [TRD]). These patients are less likely to recover with medications alone and often consider nonpharmacologic treatments such as rTMS. DATA SOURCES We searched MEDLINE, EMBASE, the Cochrane Library, PsycINFO, and the International Pharmaceutical Abstracts for studies comparing rTMS with a sham-controlled treatment in TRD patients ages 18 years or older. STUDY SELECTION We included 18 good- or fair-quality TRD studies published from January 1, 1980, through March 20, 2013. DATA EXTRACTION We abstracted relevant data, assessed each studys internal validity, and graded strength of evidence for change in depressive severity, response rates, and remission rates. RESULTS rTMS was beneficial compared with sham for all outcomes. rTMS produced a greater decrease in depressive severity (high strength of evidence), averaging a clinically meaningful decrease on the Hamilton Depression Rating Scale (HDRS) of more than 4 points compared with sham (mean decrease = -4.53; 95% CI, -6.11 to -2.96). rTMS resulted in greater response rates (high strength of evidence); those receiving rTMS were more than 3 times as likely to respond as patients receiving sham (relative risk = 3.38; 95% CI, 2.24 to 5.10). Finally, rTMS was more likely to produce remission (moderate strength of evidence); patients receiving rTMS were more than 5 times as likely to achieve remission as those receiving sham (relative risk = 5.07; 95% CI, 2.50 to 10.30). Limited evidence and variable treatment parameters prevented conclusions about which specific treatment options are more effective than others. How long these benefits persist remains unclear. CONCLUSIONS For MDD patients with 2 or more antidepressant treatment failures, rTMS is a reasonable, effective consideration.

Translating Evidence-Based Interventions Into Practice: The Design and Development of the Merck Childhood Asthma Network, Inc. (MCAN)

Pediatric asthma is a multifactorial disease, requiring complex, interrelated interventions addressing children, families, schools, and communities. The Merck Childhood Asthma Network, Inc. (MCAN) is a nonprofit organization that provides support to translate evidence-based interventions from research to practice. MCAN developed the rationale and vision for the program through a phased approach, including an extensive literature review, stakeholder engagement, and evaluation of funding gaps. The analysis pointed to the need to identify pediatric asthma interventions implemented in urban U.S. settings that have demonstrated efficacy and materials for replication and to translate the interventions into wider practice. In addition to this overall MCAN objective, specific goals included service and system integration through linkages among health care providers, schools, community-based organizations, patients, parents, and other caregivers. MCAN selected sites based on demonstrated ability to implement effective interventions and to address multiple contexts of pediatric asthma prevention and management. Selected MCAN program sites were mature institutions or organizations with significant infrastructure, existing funding, and the ability to provide services without requiring a lengthy planning period. Program sites were located in communities with high asthma morbidity and intended to integrate new elements into existing programs to create comprehensive care approaches.

The predictive validity of quality of evidence grades for the stability of effect estimates was low: a meta-epidemiological study

OBJECTIVE To determine the predictive validity of the U.S. Evidence-based Practice Center (EPC) approach to GRADE (Grading of Recommendations Assessment, Development and Evaluation). STUDY DESIGN AND SETTING Based on Cochrane reports with outcomes graded as high quality of evidence (QOE), we prepared 160 documents which represented different levels of QOE. Professional systematic reviewers dually graded the QOE. For each document, we determined whether estimates were concordant with high QOE estimates of the Cochrane reports. We compared the observed proportion of concordant estimates with the expected proportion from an international survey. To determine the predictive validity, we used the Hosmer-Lemeshow test to assess calibration and the C (concordance) index to assess discrimination. RESULTS The predictive validity of the EPC approach to GRADE was limited. Estimates graded as high QOE were less likely, estimates graded as low or insufficient QOE more likely to remain stable than expected. The EPC approach to GRADE could not reliably predict the likelihood that individual bodies of evidence remain stable as new evidence becomes available. C-indices ranged between 0.56 (95% CI, 0.47 to 0.66) and 0.58 (95% CI, 0.50 to 0.67) indicating a low discriminatory ability. CONCLUSION The limited predictive validity of the EPC approach to GRADE seems to reflect a mismatch between expected and observed changes in treatment effects as bodies of evidence advance from insufficient to high QOE.

Grades for quality of evidence were associated with distinct likelihoods that treatment effects will remain stable

OBJECTIVES We sought to determine whether producers or users of systematic reviews using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach or a close variation give the same meanings to terms intended to convey uncertainty about treatment effects when interpreting grades for the quality or strength of evidence. STUDY DESIGN AND SETTING Following exploratory interviews with stakeholders and user testing, we conducted an international Web-based survey among producers and users of systematic reviews. For each quality grade (high, moderate, low, very low/insufficient), we asked participants to assign a minimum likelihood that treatment effects will not change substantially as new studies emerge. Using multivariate analysis of covariance, we tested whether the estimated likelihoods differed between producers and users. RESULTS In all, 244 participants completed the survey. The associated minimum likelihoods that treatment effects will not change substantially for high, moderate, and low grades of quality of evidence (QOE) were 86% [95% confidence interval (CI): 85%, 87%], 61% (95% CI: 59%, 63%), and 34% (95% CI: 32%, 36%), respectively (very low was preset at 0%). Likelihoods for each grade were similar between producers and users of systematic reviews (P > 0.05 for all comparisons). CONCLUSION GRADE is, in general, a suitable method to convey uncertainties for systematic review producers to users. The wide ranges of likelihoods associated with GRADE terms suggest that current definitions of levels of QOE that rely exclusively on qualitative certainty expressions should be augmented by numerical predictions once such data are available.

Average effect estimates remain similar as evidence evolves from single trials to high-quality bodies of evidence: a meta-epidemiologic study

OBJECTIVES The objective of our study was to use a diverse sample of medical interventions to assess empirically whether first trials rendered substantially different treatment effect estimates than reliable, high-quality bodies of evidence. STUDY DESIGN AND SETTING We used a meta-epidemiologic study design using 100 randomly selected bodies of evidence from Cochrane reports that had been graded as high quality of evidence. To determine the concordance of effect estimates between first and subsequent trials, we applied both quantitative and qualitative approaches. For quantitative assessment, we used Lins concordance correlation and calculated z-scores; to determine the magnitude of differences of treatment effects, we calculated standardized mean differences (SMDs) and ratios of relative risks. We determined qualitative concordance based on a two-tiered approach incorporating changes in statistical significance and magnitude of effect. RESULTS First trials both overestimated and underestimated the true treatment effects in no discernible pattern. Nevertheless, depending on the definition of concordance, effect estimates of first trials were concordant with pooled subsequent studies in at least 33% but up to 50% of comparisons. The pooled magnitude of change as bodies of evidence advanced from single trials to high-quality bodies of evidence was 0.16 SMD [95% confidence interval (CI): 0.12, 0.21]. In 80% of comparisons, the difference in effect estimates was smaller than 0.5 SMDs. In first trials with large treatment effects (>0.5 SMD), however, estimates of effect substantially changed as new evidence accrued (mean change 0.68 SMD; 95% CI: 0.50, 0.86). CONCLUSION Results of first trials often change, but the magnitude of change, on average, is small. Exceptions are first trials that present large treatment effects, which often dissipate as new evidence accrues.

Reply to E. Grunfeld

To the Editor: We appreciate Grunfeld’s comments on our Journal of Oncology Practice article “Models of Cancer Survivorship Care: Overview and Summary of Current Evidence.” We particularly appreciate her identifying an error in the manuscript, that several citation numbers in the text did not correspond to the correct sources in the reference list. We resolved this citation source error and submitted a correction to the Journal of Oncology Practice with an updated reference list. Dr Grunfeld also points out that the sample size for one of her studies included in our analysis was incorrect. The correct sample size was listed in the Evidence Tables accompanying the Agency for Healthcare Research and Quality Technical Brief on which our article was based. We have also submitted a correction for this to Journal of Oncology Practice. Grunfeld notes that we did not include two trials and related citations despite her having notified us of these citations in a response to a request for comments on the preliminary version of the Technical Brief. We carefully reviewed her suggested citations at the time, and our responses are available at www.effectivehealthcare.ahrq.gov/ehc/products/523/ 1933/cancer-survivor-care-transition-disposition-140702.pdf. As we note in our inclusion and exclusion criteria, we sought studies that clearly demonstrated two or more services for survivorship care within one or more of the four core Institute of Medicine survivorship care components (prevention, surveillance, intervention, coordination) intended to facilitate survivors’ experience and had formal referrals to services that facilitate survivors’ experiences. In other words, we were looking for studies spanning multiple needs of a cancer survivor, rather than studies addressing single needs. Grunfeld et al (1996) and Grunfeld et al (2006) focused on routine followup, which we interpreted to mean surveillance. These studies did not, therefore, meet our inclusion criteria. Grunfeld also responds to our statement that we “found little information on usual care for cancer survivors” and lists several studies on survivorship care. The articles suggested here by Grunfeld are important studies. However, these studies present information on the number and type of physician visits and rates of receiving certain preventive care services among cancer survivors. This does not constitute the full range of “usual care” survivors may experience. For example, these studies do not provide information on two of the four aspects of survivorship care recommended by the Institute of Medicine: interventions for illnesses secondary to cancer and cancer treatment; and coordination between specialists and primary care providers to ensure that all the health needs of survivors are met. As such, they present limited information on usual care for cancer survivors. More research is needed to describe the full range of health care services received by cancer survivors as part of usual care, and how these services may differ among survivors receiving care as part of a survivorship care model. We thank Grunfeld for her careful review of our manuscript, and her comment that this article and the associated Technical Brief will serve as an important foundational document for future survivorship research.