Methods for Identifying Health Research Gaps, Needs, and Priorities: a Scoping Review.

BACKGROUND: Well-defined, systematic, and transparent processes to identify health research gaps, needs, and priorities are vital to ensuring that available funds target areas with the greatest potential for impact. OBJECTIVE: The purpose of this review is to characterize methods conducted or supported by research funding organizations to identify health research gaps, needs, or priorities. METHOD: We searched MEDLINE, PsycINFO, and the Web of Science up to September 2019. Eligible studies reported on methods to identify health research gaps, needs, and priorities that had been conducted or supported by research funding organizations. Using a published protocol, we extracted data on the method, criteria, involvement of stakeholders, evaluations, and whether the method had been replicated (i.e., used in other studies). RESULTS: Among 10,832 citations, 167 studies were eligible for full data extraction. More than half of the studies employed methods to identify both needs and priorities, whereas about a quarter of studies focused singularly on identifying gaps (7%), needs (6%), or priorities (14%) only. The most frequently used methods were the convening of workshops or meetings (37%), quantitative methods (32%), and the James Lind Alliance approach, a multi-stakeholder research needs and priority setting process (28%). The most widely applied criteria were importance to stakeholders (72%), potential value (29%), and feasibility (18%). Stakeholder involvement was most prominent among clinicians (69%), researchers (66%), and patients and the public (59%). Stakeholders were identified through stakeholder organizations (51%) and purposive (26%) and convenience sampling (11%). Only 4% of studies evaluated the effectiveness of the methods and 37% employed methods that were reproducible and used in other studies. DISCUSSION: To ensure optimal targeting of funds to meet the greatest areas of need and maximize outcomes, a much more robust evidence base is needed to ascertain the effectiveness of methods used to identify research gaps, needs, and priorities.

Combat and Operational Stress Control Interventions and PTSD: A Systematic Review and Meta-Analysis.

INTRODUCTION: Military personnel must prepare for and respond to life-threatening crises on a daily basis. This lifestyle places stress on personnel, and particularly so on deployed service members who are isolated from support systems and other resources. As part of a larger systematic review on the acceptability, efficacy, and comparative effectiveness of interventions designed to prevent, identify, and manage stress reactions, we assessed posttraumatic stress disorder (PTSD) outcomes. MATERIALS AND METHODS: We searched the electronic databases PsycINFO, PubMed, PTSDPubs, the Defense Technical Information Center, and Cochrane Central, as well as bibliographies of existing systematic reviews, to identify English-language studies evaluating the efficacy or comparative effectiveness of stress control interventions published since 1990. Controlled trials and cohort comparisons of interventions with military, law enforcement, and first responders were included. Two independent reviewers screened literature using predetermined eligibility criteria. Researchers individually abstracted study-level information and outcome data and assessed the risk of bias of included studies; data were reviewed for accuracy by the project leader. Changes in PTSD symptom scores from baseline to post-intervention were converted to standardized mean differences for comparison across studies. Risk ratios were calculated for PTSD case rates post-deployment. When several studies that compared an intervention group with a similar control/comparator reported the same outcome category and measure type, we conducted meta-analysis. We conducted meta-regression by adding a categorical variable, representing setting (i.e., in theater) or population (military vs. law enforcement or first responders) to the meta-analysis model to assess whether this variable was associated with the outcome across studies. The quality of the body of evidence (QoE) was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, which considers study limitations (risk of bias), directness, consistency, precision, and publication bias. RESULTS: Sixteen controlled trials and 13 cohort comparisons reporting PTSD outcomes met inclusion criteria. Eight controlled trials and two cohort studies had high risk of bias, primarily due to poor, differential, or unknown response rate at follow-up. Twenty-four of the 29 studies included military personnel. Interventions included Acceptance-based Skills training, Attention Bias Modification training, stress inoculation with biofeedback, Critical Incident Stress Debriefing, group psychological debriefing, Eye Movement Desensitization and Reprocessing for sub-clinical stress, embedding mental health providers in theater, Third Location Decompression, reintegration programs, and a 3-week post-deployment residential program for psychological resource strengthening.Meta-analyses of studies comparing a group that received a stress control intervention to a group that did not receive an intervention found no significant difference in reduction in PTSD symptom scores (moderate QoE) or PTSD case rate post-deployment (low QoE). A meta-analysis of studies comparing a specific stress control intervention to an active comparator (usually standard stress management education) found no significant effect on PTSD symptom scores (moderate QoE). CONCLUSION: Although combat and operational stress control (COSC) interventions may play a valuable role in decreasing stress, decreasing absenteeism, and enabling return to duty, a systematic review of 29 studies that included a control/comparison group found little evidence that COSC is effective in preventing PTSD or decreasing PTSD symptom scores in military personnel.

Differences in lymphoma patients between chimeric antigen receptor T-cell therapy trials and the general population.

Chimeric antigen receptor (CAR)-T cell therapies appear to be promising treatments for non-Hodgkin's and B-cell lymphoma. However, several CAR-T therapies approved by the US Food and Drug Administration have only been tested for efficacy in relatively few single-arm clinical trials with small sample sizes. We sought to examine the differences between patients in these trials and the general population of patients with non-Hodgkin's and B-cell lymphoma. Five hundred and twenty-two patients from 15 CAR-T trials found in a systematic review and 417,492 patients from the Surveillance, Epidemiology, and End Results (SEER) Program database were compared. CAR-T study participants appeared to be younger (46.7% under 70 years old vs. 42.2%), more male (68.0% vs. 55.7%), and followed for a shorter period of time compared to patients in the SEER population (mean [M] 45.6 months, 95% confidence interval [CI] 17.7 to 63.3 months follow-up vs. M 57.1 months, 95% CI 57.0 to 57.3 months survival). CAR-T study participants may differ significantly from the general population of patients with non-Hodgkin's and B-cell lymphoma. Effectiveness of CAR-T therapies in the general population of lymphoma patients may differ from effectiveness demonstrated in trials. Newly created CAR-T patient registries are essential to establishing population-level effectiveness of the therapies.

Radiation Therapy for Brain Metastases: A Systematic Review.

PURPOSE: This evidence report synthesizes the available evidence on radiation therapy for brain metastases. METHODS AND MATERIALS: The literature search included PubMed, EMBASE, Web of Science, Scopus, CINAHL, clinicaltrials.gov, and published guidelines in July 2020; independently submitted data, expert consultation, and contacting authors. Included studies were randomized controlled trials (RCTs) and large observational studies (for safety assessments), evaluating whole brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS) alone or in combination, as initial or postoperative treatment, with or without systemic therapy for adults with brain metastases due to lung cancer, breast cancer, or melanoma. RESULTS: Ninety-seven studies reported in 189 publications were identified, but the number of analyses was limited owing to different intervention and comparator combinations as well as insufficient reporting of outcome data. Risk of bias varied, and 25 trials were terminated early, predominantly owing to poor accrual. The combination of SRS plus WBRT compared with SRS alone or WBRT alone showed no statistically significant difference in overall survival (hazard ratio [HR], 1.09; 95% confidence interval [CI], 0.69%-1.73%; 4 RCTs) or death owing to brain metastases (relative risk [RR], 0.93; 95% CI, 0.48%-1.81%; 3 RCTs). Radiation therapy after surgery did not improve overall survival compared with surgery alone (HR, 0.98; 95% CI, 0.76%-1.26%; 5 RCTs). Data for quality of life, functional status, and cognitive effects were insufficient to determine effects of WBRT, SRS, or postsurgery interventions. We did not find systematic differences across interventions in serious adverse events, number of adverse events, radiation necrosis, fatigue, or seizures. WBRT plus systemic therapy (RR 1.44; 95% CI, 1.03%-2.00%; 14 studies) was associated with increased risks for vomiting compared with WBRT alone. CONCLUSIONS: Despite the substantial research literature on radiation therapy, comparative effectiveness information is limited. There is a need for more data on patient-relevant outcomes such as quality of life, functional status, and cognitive effects.

An evidence map of randomised controlled trials evaluating genetic therapies.

OBJECTIVES: Genetic therapies replace or inactivate disease-causing genes or introduce new or modified genes. These therapies have the potential to cure in a single application rather than treating symptoms through repeated administrations. This evidence map provides a broad overview of the genetic therapies that have been evaluated in randomised controlled trials (RCTs) for efficacy and safety. ELIGIBILITY CRITERIA: Two independent reviewers screened publications using predetermined eligibility criteria. Study details and data on safety and efficacy were abstracted from included trials. Results were visualised in an evidence map. INFORMATION SOURCES: We searched PubMed, EMBASE, Web of Science, ClinicalTrials.gov and grey literature to November 2018. RISK OF BIAS: Only RCTs were included in this review to reduce the risk of selection bias in the evaluation of genetic therapy safety and efficacy. INCLUDED STUDIES: We identified 119 RCTs evaluating genetic therapies for a variety of clinical conditions. SYNTHESIS OF RESULTS: On average, samples included 107 participants (range: 1-1022), and were followed for 15 months (range: 0-124). Interventions using adenoviruses (40%) to treat cardiovascular diseases (29%) were the most common. DESCRIPTION OF THE EFFECT: In RCTs reporting safety and efficacy outcomes, in the majority (60%) genetic therapies were associated with improved symptoms but in nearly half (45%) serious adverse event (SAEs) were also reported. Improvement was reported in trials treating cancer, cardiovascular, ocular and muscular diseases. However, only 19 trials reported symptom improvement for at least 1 year. STRENGTHS AND LIMITATIONS OF EVIDENCE: This is the first comprehensive evidence map of RCTs evaluating the safety and efficacy of genetic therapies. Evidence for long-term effectiveness and safety is still sparse. This lack of evidence has implications for the use, ethics, pricing and logistics of genetic therapies. INTERPRETATION: This evidence map provides a broad overview of research studies that allow strong evidence statements regarding the safety and efficacy of genetic therapies. Most interventions improve symptoms, but SAE are also common. More research is needed to evaluate genetic therapies with regard to the potential to cure diseases.

A Systematic Review in Support of the National Consensus Project Clinical Practice Guidelines for Quality Palliative Care, Fourth Edition.

CONTEXT: Palliative care continues to be a rapidly growing field aimed at improving quality of life for patients and their caregivers. OBJECTIVES: The purpose of this review was to provide a synthesis of the evidence in palliative care to inform the fourth edition of the National Consensus Project Clinical Practice Guidelines for Quality Palliative Care. METHODS: Ten key review questions addressing eight content domains guided a systematic review focused on palliative care interventions. We searched eight databases in February 2018 for systematic reviews published in English from 2013, after the last edition of National Consensus Project guidelines was published, to present. Experienced literature reviewers screened, abstracted, and appraised data per a detailed protocol registered in PROSPERO. The quality of evidence was evaluated using the Grading of Recommendations, Assessment, Development and Evaluations criteria. The review was supported by a technical expert panel. RESULTS: We identified 139 systematic reviews meeting inclusion criteria. Reviews addressed the structure and process of care (interdisciplinary team care, 13 reviews; care coordination, 18 reviews); physical aspects (48 reviews); psychological aspects (26 reviews); social aspects (two reviews); spiritual, religious, and existential aspects (11 reviews); cultural aspects (three reviews); care of the patient nearing the end of life (grief/bereavement programs, six reviews; final days of life, two reviews); ethical and legal aspects (36 reviews). CONCLUSION: A substantial body of evidence exists to support clinical practice guidelines for quality palliative care, but the quality of evidence is limited.