Innovations in data collection, management, and archiving for systematic reviews.

Data abstraction is a key step in conducting systematic reviews because data collected from study reports form the basis of appropriate conclusions. Recent methodological standards and expectations highlight several principles for data collection. To support implementation of these standards, this article provides a step-by-step tutorial for selecting data collection tools; constructing data collection forms; and abstracting, managing, and archiving data for systematic reviews. Examples are drawn from recent experience using the Systematic Review Data Repository for data collection and management. If it is done well, data collection for systematic reviews only needs to be done by 1 team and placed into a publicly accessible database for future use. Technological innovations, such as the Systematic Review Data Repository, will contribute to finding trustworthy answers for many health and health care questions.

Asymptomatic carotid artery stenosis treated with medical therapy alone: temporal trends and implications for risk assessment and the design of future studies.

BACKGROUND: The rate of adverse clinical outcomes among patients with asymptomatic carotid stenosis receiving medical therapy alone can be used to guide clinical decision-making and to inform future research. We aimed to investigate temporal changes in the incidence rate of clinical outcomes among patients with asymptomatic carotid stenosis receiving medical therapy alone and to explore the implications of these changes for the design of future comparative studies. SUMMARY: We searched MEDLINE, the Cochrane Central Register of Controlled Trials, US Food and Drug Administration documents, and reference lists of included studies (last search: December 31, 2012). We selected prospective cohort studies of medical therapy for asymptomatic carotid artery stenosis and we extracted information on study characteristics, risk of bias, and outcomes. We performed meta-analyses to estimate summary incidence rates, meta-regressions to assess trends over time, and simulations to explore sample size requirements for the design of future studies comparing new treatments against medical therapy. The main outcomes of interest were ipsilateral stroke, any stroke, cardiovascular death, death, and myocardial infarction. We identified 41 studies of medical therapy for patients with asymptomatic carotid stenosis (last recruitment year: 1978-2009). The summary incidence rate of ipsilateral carotid territory stroke (25 studies) was 1.7 per 100 person-years. This incidence rate was significantly lower in recent studies (last recruitment year from 2000 onwards) as compared to studies that ended recruitment earlier (1.0 vs. 2.3 events per 100 person-years; p < 0.001). The incidence rates of any territory stroke (17 studies), cardiovascular death (6 studies), death (13 studies), and myocardial infarction (5 studies) were 2.7, 4.1, 4.6, and 1.8 per 100 person-years, respectively. Simulations showed that future studies would need to enroll large numbers of patients with a relatively high incidence rate under medical therapy, and evaluate interventions with large effect sizes, to have adequate power to reliably detect treatment effects. KEY MESSAGES: Improved prognosis under medical therapy alone has narrowed the potential range of risk reduction attainable with new treatments for asymptomatic carotid stenosis. Future comparative studies will need to enroll large numbers of patients to assess treatment effectiveness.

A community consultation survey to evaluate support for and success of the IMMEDIATE trial.

BACKGROUND: The IMMEDIATE (Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency care) Trial, a randomized controlled double-blind clinical effectiveness trial of glucose-insulin-potassium (GIK) administered in ambulances in the out-of-hospital setting, used the Exception from Informed Consent Requirements (EFIC) for Emergency Research under Title 21 of the Code of Federal Regulations. EFIC requirements include community consultation that typically involves using a variety of communication methods and venues to inform the public of the research and to receive their feedback. Although not the primary purpose of the community consultation process, a common concern to research sponsors, staff, and institutional review boards (IRBs) is whether there will be a sufficient number of participants to justify mounting a study in their community. Information from community consultation regarding the community acceptance might inform this question. PURPOSE: We evaluated the utility of telephone survey data done as part of the EFIC process as a way to project the ultimate rate of trial participant enrollment. METHODS: A telephone survey community consultation process was undertaken in nine communities planning to be IMMEDIATE Trial sites using a representative sampling of the target population in the areas covered by participating emergency medical service (EMS) agencies. Survey respondents were read a description of the planned study and its informed consent approach that included the option for patients to decline participation in the trial while being transported for acute care in an ambulance. Survey respondents were then asked whether they would object to participating in the study. At the conclusion of actual trial enrollment, the Coordinating Center compared the survey results with the actual rates of enrollment at each site. RESULTS: Approximately 200 (range = 200-271) respondents completed the survey in each of the study communities. Of 2079 survey respondents, 68% (range = 61%-75%) said that they would not object to participating in the trial if experiencing a heart attack, and 85% (range = 79%-89%) said that they would allow the study to be done in their community. During actual trial enrollment in the communities, 79% (range = 63%-91%) of the 828 potential participants agreed in the ambulance to have the study drug started and provided informed consent at the hospital, an average of 13 percentage-points higher than projected by the survey (95% confidence interval (CI): 9%-17%), 19% higher on a relative scale (CI: 14%-25%). CONCLUSIONS: The survey-based approach to community consultation proved to be an efficient way to obtain representative input from potential clinical trial participants. The survey data generated a relatively good and conservative estimate of the ultimate rate of trial enrollment. This information could be useful to investigators and IRBs in projecting enrollment for clinical trials using EFIC.

Management strategies for asymptomatic carotid stenosis: a systematic review and meta-analysis.

BACKGROUND: Adults with asymptomatic carotid artery stenosis are at increased risk for ipsilateral carotid territory ischemic stroke. PURPOSE: To examine comparative evidence on management strategies for asymptomatic carotid stenosis and the incidence of ipsilateral stroke with medical therapy alone. DATA SOURCES: MEDLINE, Cochrane Central Register of Controlled Trials, U.S. Food and Drug Administration documents, and review of references through 31 December 2012. STUDY SELECTION: Randomized, controlled trials (RCTs) and prospective or retrospective nonrandomized, comparative studies of medical therapy alone, carotid endarterectomy (CEA) plus medical therapy, or carotid artery stenting (CAS) plus medical therapy for adults with asymptomatic carotid stenosis, as well as single-group prospective cohort studies of medical therapy, were reviewed. DATA EXTRACTION: Two investigators extracted information on study and population characteristics, results, and risk of bias. DATA SYNTHESIS: Forty-seven studies in 56 publications were eligible. The RCTs comparing CAS and CEA were clinically heterogeneous; 1 RCT reported more but not statistically significant ipsilateral stroke events (including any periprocedural stroke) in CAS compared with CEA, whereas another RCT, in a population at high surgical risk for CEA, did not. Three RCTs showed that CEA reduced the risk for ipsilateral stroke (including any periprocedural stroke) compared with medical therapy alone, but these results may no longer be applicable to contemporary clinical practice. No RCT compared CAS versus medical therapy alone. The summary incidence of ipsilateral stroke across 26 cohorts receiving medical therapy alone was 1.68% per year. LIMITATIONS: Studies defined asymptomatic status heterogeneously. Participants in RCTs did not receive best-available medical therapy. CONCLUSION: Future RCTs of asymptomatic carotid artery stenosis should explore whether revascularization interventions provide benefit to patients treated by best-available medical therapy. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Emerging magnetic resonance imaging technologies for musculoskeletal imaging under loading stress: scope of the literature.

Imaging under loading stress is hypothesized to improve the diagnostic value of magnetic resonancel imaging (MRI) for musculoskeletal conditions. This article reviews 57 studies about MRI under physiologic loading stress performed in an upright or sitting position or under axial loading by using a compression device. The most commonly imaged regions were the spine (33 studies) and knee (13 studies). Most studies had a cross-sectional (n = 37) or case-control (n = 13) design and reported on anatomical measurements rather than patient-relevant end points. Studies were generally small: The median (25th, 75th percentile) number of case patients was 26 (17, 45), and the median (25th, 75th percentile) number of control participants was 13 (12, 20 for case-control studies). Fifteen of 57 studies used at least 2 imaging tests and reported on diagnostic or patient-relevant outcomes but did not report meaningful information on the relative performance of the tests. In 10 studies that included information on adverse effects, 5% to 15% of participants reported new-onset or worsening pain and neuropathy during MRI under loading stress. Overall, evidence is insufficient to support the clinical utility of MRI under loading stress for musculoskeletal conditions.

Combined immunotherapy with controlled interleukin-12 gene therapy and immune checkpoint blockade in recurrent glioblastoma: An open-label, multi-institutional phase I trial.

BACKGROUND: Veledimex (VDX)-regulatable interleukin-12 (IL-12) gene therapy in recurrent glioblastoma (rGBM) was reported to show tumor infiltration of CD8+ T cells, encouraging survival, but also up-regulation of immune checkpoint signaling, providing the rationale for a combination trial with immune checkpoint inhibition. METHODS: An open-label, multi-institutional, dose-escalation phase I trial in rGBM subjects (NCT03636477) accrued 21 subjects in 3 dose-escalating cohorts: (1) neoadjuvant then ongoing nivolumab (1mg/kg) and VDX (10 mg) (n = 3); (2) neoadjuvant then ongoing nivolumab (3 mg/kg) and VDX (10 mg) (n = 3); and (3) neoadjuvant then ongoing nivolumab (3 mg/kg) and VDX (20 mg) (n = 15). Nivolumab was administered 7 (±3) days before resection of the rGBM followed by peritumoral injection of IL-12 gene therapy. VDX was administered 3 hours before and then for 14 days after surgery. Nivolumab was administered every two weeks after surgery. RESULTS: Toxicities of the combination were comparable to IL-12 gene monotherapy and were predictable, dose-related, and reversible upon withholding doses of VDX and/or nivolumab. VDX plasma pharmacokinetics demonstrate a dose-response relationship with effective brain tumor tissue VDX penetration and production of IL-12. IL-12 levels in serum peaked in all subjects at about Day 3 after surgery. Tumor IFNγ increased in post-treatment biopsies. Median overall survival (mOS) for VDX 10 mg with nivolumab was 16.9 months and for all subjects was 9.8 months. CONCLUSION: The safety of this combination immunotherapy was established and has led to an ongoing phase II clinical trial of immune checkpoint blockade with controlled IL-12 gene therapy (NCT04006119).

Symptom clusters and physical function for patients receiving chemotherapy.

OBJECTIVES: To examine the literature on symptom clusters and the impact of co-occurring symptoms on the physical function of patients with cancer during treatment. DATA SOURCES: Research and review articles. CONCLUSION: Unmanaged symptoms occur in what are often called symptom clusters. A focus on known and frequently present co-occurring symptoms, such as pain, fatigue, and sleep disturbance, might be the most efficient and effective way to manage specific symptoms and improve patient functioning. IMPLICATIONS FOR NURSING PRACTICE: Nurses should select assessments that identify multiple symptoms and define their co-occurrence.

A Structured Approach Using the Systematic Review Data Repository (SRDR): Building the Evidence for Oral Health Interventions in the Population With Intellectual and Developmental Disability.

BACKGROUND: This review describes the methods used for a systematic review of oral health intervention literature in a target population (people with intellectual and developmental disability (I/DD)), which spans a broad range of interventions and study types, conducted with specialized software. OBJECTIVE: The aim of this article is to demonstrate the review strategy, using the free, online systematic review data repository (SRDR) tool, for oral health interventions aimed at reducing disparities between people with I/DD and the general population. RESEARCH DESIGN: Researchers used online title/abstract review (Abstrackr) and data extraction (SRDR) tools to structure the literature review and data extraction. A practicing clinician and an expert methodologist completed the quality review for each study. The data extraction team reported on the experience of using and customizing the SRDR. RESULTS: Using the SRDR, the team developed four extraction templates for eight key questions and completed extraction on 125 articles. CONCLUSIONS: This report discusses the advantages and disadvantages of using an electronic tool, such as the SRDR, in completing a systematic review in an area of growing research. This review provides valuable insight for researchers who are considering the use of the SRDR.

The lack of evidence for PET or PET/CT surveillance of patients with treated lymphoma, colorectal cancer, and head and neck cancer: a systematic review.

UNLABELLED: PET and PET/CT are widely used for surveillance of patients after cancer treatments. We conducted a systematic review to assess the diagnostic accuracy and clinical impact of PET and PET/CT used for surveillance in several cancers. METHODS: We searched MEDLINE and Cochrane Library databases from 1996 to March 2012 for English-language studies of PET or PET/CT used for surveillance of patients with lymphoma, colorectal cancer, or head and neck cancer. We included prospective or retrospective studies that reported test accuracy and comparative studies that assessed clinical impact. RESULTS: Twelve studies met our inclusion criteria: 6 lymphoma (n = 767 patients), 2 colorectal cancer (n = 96), and 4 head and neck cancer (n = 194). All studies lacked a uniform definition of surveillance and scan protocols. Half the studies were retrospective, and a third were rated as low quality. The majority reported sensitivities and specificities in the range of 90%-100%, although several studies reported lower results. The only randomized controlled trial, a colorectal cancer study with 65 patients in the surveillance arm, reported earlier detection of recurrences with PET and suggested improved clinical outcomes. CONCLUSION: There is insufficient evidence to draw conclusions on the clinical impact of PET or PET/CT surveillance for these cancers. The lack of standard definitions for surveillance, heterogeneous scanning protocols, and inconsistencies in reporting test accuracy preclude making an informed judgment on the value of PET for this potential indication.

A Web-based archive of systematic review data.

Systematic reviews have become increasingly critical to informing healthcare policy; however, they remain a time-consuming and labor-intensive activity. The extraction of data from constituent studies comprises a significant portion of this effort, an activity which is often needlessly duplicated, such as when attempting to update a previously conducted review or in reviews of overlapping topics.In order to address these inefficiencies, and to improve the speed and quality of healthcare policy- and decision-making, we have initiated the development of the Systematic Review Data Repository, an open collaborative Web-based repository of systematic review data. As envisioned, this resource would serve as both a central archive and data extraction tool, shared among and freely accessible to organizations producing systematic reviews worldwide. A suite of easy-to-use software tools with a Web frontend would enable researchers to seamlessly search for and incorporate previously deposited data into their own reviews, as well as contribute their own.In developing this resource, we identified a number of technical and non-technical challenges, as well as devised a number of potential solutions, including proposals for systems and software tools to assure data quality, stratify and control user access effectively and flexibly accommodate all manner of study data, as well as means by which to govern and foster adoption of this new resource.Herein we provide an account of the rationale and development of the Systematic Review Data Repository thus far, as well as outline its future trajectory.