Role of Isolated Limb Perfusion in the Era of Targeted Therapies and Immunotherapy in Melanoma. A Systematic Review of The Literature

Background. Isolated limb perfusion (ILP) is a locoregional procedure indicated by the unresectable melanoma of the limbs. Its complexity and highly demanding multidisciplinary approach means that it is a technique only implemented in a few referral centers around the globe. This report aims to examine its potential role in the era of targeted therapies and immunotherapy by conducting a systematic review of the literature on ILP. Methods. PubMed, Embase and Cochrane Library were searched. The eligibility criteria included publications from 2000–2020 providing valid data o effectiveness, survival or toxicity. Studies in which the perfusion methodology was not clearly described, letters to the editor, non-systematic reviews and studies that applied outdated clinical guidelines were excluded. To rule out studies of a low methodological quality and assess the risk of bias, the following aspects were also required: a detailed description of the applied ILP regimen, the clinical context, follow-up periods, analyzed clinical endpoints, and the number of analyzed ILPs. The disagreements were resolved by consensus. The results are presented in tables and figures. Results. Twenty-seven studies including 2637 ILPs were selected. The median overall response rate was 85%, with a median complete response rate of 58.5%. The median overall survival was 38 months, with a 5-year overall survival of 35%. The toxicity was generally mild according to Wieberdink toxicity criteria. Discussion. ILP still offer a high efficacy in selected patients. The main limitation of our review is the heterogeneity and age of most of the articles, as well as the absence of clinical trials comparing ILP with other procedures, making it difficult to transfer its results to the current era. Conclusions. ILP is still an effective and safe procedure for selected patients with unresectable melanoma of the limbs. In the era of targeted therapies and immunotherapy, ILP remains an acceptable and reasonable palliative treatment alternative, especially to avoid limb amputations. The ongoing clinical trials combining systemic therapies and ILP will provide more valuable information in the future to clarify the potential synergism of both strategies.

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Crizotinib Versus Chemotherapy on ALK-positive NSCLC: A Systematic Review of Efficacy and Safety

Current Cancer Drug Targets ◽

10.2174/1568009617666170623115846 ◽

2018 ◽

Vol 19 (1) ◽

pp. 41-49 ◽

Cited By ~ 2

Author(s):

Mingxia Wang ◽

Guanqi Wang ◽

Haiyan Ma ◽

Baoen Shan

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Adverse Events ◽

Objective Response Rate ◽

Retrospective Studies ◽

Response Rate ◽

Objective Response ◽

Treated Group ◽

Efficacy And Safety ◽

Alk Positive

Introduction: Crizotinib was approved to treat anaplastic lymphoma kinase (ALK)- positive non-small cell lung cancer (NSCLC) by the Food and Drug Administration in 2011.We conducted a systematic review of clinical trials and retrospective studies to compare the efficacy and safety of crizotinib with chemotherapy. </P><P> Methods: We searched electronic databases from inception to Dec. 2016. Clinical trials and retrospective studies regarding crizotinib and crizotinib versus chemotherapy in treatment of NSCLC were eligible. The primary outcomes were the objective response rate (ORR) and disease control rate (DCR). Results: Nine studies (five clinical trials and four retrospective studies) including 729 patients met the inclusion criteria. Crizotinib treatment revealed 1-year OS of 77.1% and PFS of 9.17 months. And crizotinib had a better performance than chemotherapy in ORR (OR: 4.97, 95%CI: 3.16 to 7.83, P<0.00001, I2=35%). DCR revealed superiority with crizotinib than chemotherapy (OR: 3.42, 95% CI: 2.33 to 5.01, P<0.00001, I2=0%). PR (partial response) were significant superior to that of chemotherapy through direct systematic review. No statistically significant difference in CR (complete response) was found between crizotinib-treated group and chemotherapy-treated group. Regarding SD (stable disease), chemotherapy-treated group had a better performance than crizotinib-treated group. Common adverse events associated with crizotinib were visual disorder, gastrointestinal side effects, and elevated liver aminotransferase levels, whereas common adverse events with chemotherapy were fatigue, nausea, and hematologic toxicity. This systematic review revealed improved objective response rate and increased disease control rate in crizotinib group comparing with chemotherapy group. Crizotinib treatment would be a favorable treatment option for patients with ALK-positive NSCLC. ALK inhibitors may have future potential applications in other cancers driven by ALK or c-MET gene mutations.

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Efficacy of dialectical behavior therapy for adolescent self-harm and suicidal ideation: a systematic review and meta-analysis

Psychological Medicine ◽

10.1017/s0033291721001355 ◽

2021 ◽

pp. 1-11

Author(s):

Oswald D. Kothgassner ◽

Andreas Goreis ◽

Kealagh Robinson ◽

Mercedes M. Huscsava ◽

Christian Schmahl ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Suicidal Ideation ◽

Dialectical Behavior Therapy ◽

Meta Analysis ◽

Adolescent Psychopathology ◽

Cochrane Library ◽

Behaviour Therapy ◽

Clinical Consequences ◽

Self Harm

Abstract Background Given the widespread nature and clinical consequences of self-harm and suicidal ideation among adolescents, establishing the efficacy of developmentally appropriate treatments that reduce both self-harm and suicidal ideation in the context of broader adolescent psychopathology is critical. Methods We conducted a systematic review and meta-analysis of the Dialectical Behaviour Therapy for Adolescents (DBT-A) literature on treating self-injury in adolescents (12–19 years). We searched for eligible trials and treatment evaluations published prior to July 2020 in MEDLINE/PubMed, Scopus, Google Scholar, EMBASE, and the Cochrane Library databases for clinical trials. Twenty-one studies were identified [five randomized-controlled trials (RCTs), three controlled clinical trials (CCTs), and 13 pre-post evaluations]. We extracted data for predefined primary (self-harm, suicidal ideation) and secondary outcomes (borderline personality symptoms; BPD) and calculated treatment effects for RCTs/CCTs and pre-post evaluations. This meta-analysis was pre-registered with OSF: osf.io/v83e7. Results Overall, the studies comprised 1673 adolescents. Compared to control groups, DBT-A showed small to moderate effects for reducing self-harm (g = −0.44; 95% CI −0.81 to −0.07) and suicidal ideation (g = −0.31, 95% CI −0.52 to −0.09). Pre-post evaluations suggested large effects for all outcomes (self-harm: g = −0.98, 95% CI −1.15 to −0.81; suicidal ideation: g = −1.16, 95% CI −1.51 to −0.80; BPD symptoms: g = −0.97, 95% CI −1.31 to −0.63). Conclusions DBT-A appears to be a valuable treatment in reducing both adolescent self-harm and suicidal ideation. However, evidence that DBT-A reduces BPD symptoms was only found in pre-post evaluations.

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Cardiovascular Toxicities Secondary to Biotherapy and Molecular Targeted Therapies in Neuroendocrine Neoplasms: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials

Cancers ◽

10.3390/cancers13092159 ◽

2021 ◽

Vol 13 (9) ◽

pp. 2159

Author(s):

Charalampos Aktypis ◽

Maria-Eleni Spei ◽

Maria Yavropoulou ◽

Göran Wallin ◽

Anna Koumarianou ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Adverse Effects ◽

Targeted Therapies ◽

Safety Profile ◽

Meta Analysis ◽

Mtor Inhibitors ◽

Risk Of Bias ◽

Neuroendocrine Neoplasms ◽

Controlled Trials

A broad spectrum of novel targeted therapies with prime antitumor activity and/or ample control of hormonal symptoms together with an overall acceptable safety profile have emerged for patients with metastatic neuroendocrine neoplasms (NENs). In this systematic review and quantitative meta-analysis, the PubMed, EMBASE, Cochrane Central Register of Controlled Trials and clinicaltrials.gov databases were searched to assess and compare the safety profile of NEN treatments with special focus on the cardiovascular adverse effects of biotherapy and molecular targeted therapies (MTTs). Quality/risk of bias were assessed using GRADE criteria. Placebo-controlled randomized clinical trials (RCTs) in patients with metastatic NENs, including medullary thyroid cancer (MTC) were included. A total of 3695 articles and 122 clinical trials registered in clinicaltrials.gov were screened. We included sixteen relevant RCTs comprising 3408 unique patients assigned to different treatments compared with placebo. All the included studies had a low risk of bias. We identified four drug therapies for NENs with eligible placebo-controlled RCTs: somatostatin analogs (SSAs), tryptophan hydroxylase (TPH) inhibitors, mTOR inhibitors and tyrosine kinase inhibitors (TKI). Grade 3 and 4 adverse effects (AE) were more often encountered in patients treated with mTOR inhibitors and TKI (odds ratio [OR]: 2.42, 95% CI: 1.87–3.12 and OR: 3.41, 95% CI: 1.46–7.96, respectively) as compared to SSAs (OR:0.77, 95% CI: 0.47–1.27) and TPH inhibitors (OR:0.77, 95% CI: 0.35–1.69). MTOR inhibitors had the highest risk for serious cardiac AE (OR:3.28, 95% CI: 1.66–6.48) followed by TKIs (OR:1.51, 95% CI: 0.59–3.83). Serious vascular AE were more often encountered in NEN patients treated with mTOR inhibitors (OR: 1.72, 95% CI: 0.64–4.64) and TKIs (OR:1.64, 95% CI: 0.35–7.78). Finally, patients on TKIs were at higher risk for new-onset or exacerbation of pre-existing hypertension (OR:3.31, 95% CI: 1.87–5.86). In conclusion, SSAs and TPH inhibitors appear to be safer as compared to mTOR inhibitors and TKIs with regards to their overall toxicity profile, and cardiovascular toxicities in particular. Special consideration should be given to a patient-tailored approach with anticipated toxicities of targeted NEN treatments together with assessment of cardiovascular comorbidities, assisting clinicians in treatment selection and early recognition/management of cardiovascular toxicities. This approach could improve patient compliance and preserve cardiovascular health and overall quality of life.

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The Current Role of Immunotherapy in mCRPC: A Systematic Review

Austin Journal of Clinical Case Reports ◽

10.26420/austinjclincaserep.2021.1222 ◽

2021 ◽

Vol 8 (7) ◽

Author(s):

Dalibey H ◽

◽

Hansen TF ◽

Zedan AH ◽

◽

...

Keyword(s):

Prostate Cancer ◽

Systematic Review ◽

Overall Survival ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Response Rate ◽

Checkpoint Inhibitors ◽

Specific Antigen ◽

Treatment Modalities ◽

Significant Difference

Background: The development of immunotherapy has shown promising results in several malignant diseases, including prostate cancer, calling for a systematic review of the current literature. This review aims to evaluate the present data and prospects of immune checkpoint inhibitors in metastatic Castration Resistant Prostate Cancer (mCRPC). Methods: Articles were identified via a systematic search of the electronic database Pubmed, in accordance with the PICO process and following the PRISMA guidelines. Articles in English studying immune checkpoint inhibitors in patients with mCRPC published between March 2010 and March 2020 were eligible for inclusion. Endpoints of interest were Overall Survival (OS), Progression-Free Survival (PFS), clinical Overall Response Rate (ORR), and Prostate-Specific Antigen (PSA) response rate. Results: Ten articles were identified as eligible for inclusion. The studies primarily explored the use of Ipilimumab, a CTLA-4 inhibitor, and Pembrolizumab, a PD-1 inhibitor. These drugs were both used either as monotherapy or in combination with other treatment modalities. The largest trial included in the review demonstrated no significant difference in overall survival between the intervention and placebo. However, two studies presented promising data combing immunotherapy and immune vaccines. Grade 3 and 4 adverse events ranging from 10.1% to 82.3%, whit diarrhea, rash, and fatigue were the most frequently reported. Forty relevant ongoing trials were identified exploring immunotherapy with or without a parallel treatment modality. Conclusion: Overall, the current data shows that the effect of immune checkpoint inhibitors as monotherapy may have limited impact on mCRPC, and the results from ongoing combinational trials are eagerly awaited.

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Nervous and Muscular Adverse Events after COVID-19 Vaccination: A Systematic Review and Meta-Analysis of Clinical Trials

Vaccines ◽

10.3390/vaccines9080939 ◽

2021 ◽

Vol 9 (8) ◽

pp. 939

Author(s):

Jiaxin Chen ◽

Yuangui Cai ◽

Yicong Chen ◽

Anthony P. Williams ◽

Yifang Gao ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Adverse Events ◽

Fixed Effects ◽

Meta Analysis ◽

Phase 1 ◽

Cochrane Library ◽

Categorical Variables ◽

Control Group ◽

Open Label

Background: Nervous and muscular adverse events (NMAEs) have garnered considerable attention after the vaccination against coronavirus disease (COVID-19). However, the incidences of NMAEs remain unclear. We aimed to calculate the pooled event rate of NMAEs after COVID-19 vaccination. Methods: A systematic review and meta-analysis of clinical trials on the incidences of NMAEs after COVID-19 vaccination was conducted. The PubMed, Medline, Embase, Cochrane Library, and Chinese National Knowledge Infrastructure databases were searched from inception to 2 June 2021. Two independent reviewers selected the study and extracted the data. Categorical variables were analyzed using Pearson’s chi-square test. The pooled odds ratio (OR) with the corresponding 95% confidence intervals (CIs) were estimated and generated with random or fixed effects models. The protocol of the present study was registered on PROSPERO (CRD42021240450). Results: In 15 phase 1/2 trials, NMAEs occurred in 29.2% vs. 21.6% (p < 0.001) vaccinated participants and controls. Headache and myalgia accounted for 98.2% and 97.7%, and their incidences were 16.4% vs. 13.9% (OR = 1.97, 95% CI = 1.28–3.06, p = 0.002) and 16.0% vs. 7.9% (OR = 3.31, 95% CI = 2.05–5.35, p < 0.001) in the vaccine and control groups, respectively. Headache and myalgia were more frequent in the newly licensed vaccines (OR = 1.97, 95% CI = 1.28–3.06, p = 0.02 and OR = 3.31, 95% CI = 2.05–5.35, p < 0.001) and younger adults (OR = 1.40, 95% CI = 1.12–1.75, p = 0.003 and OR = 1.54, 95% CI = 1.20–1.96, p < 0.001). In four open-label trials, the incidences of headache, myalgia, and unsolicited NMAEs were 38.7%, 27.4%, and 1.5%. Following vaccination in phase 3 trials, headache and myalgia were still common with a rate of 29.5% and 19.2%, although the unsolicited NMAEs with incidence rates of ≤ 0.7% were not different from the control group in each study. Conclusions: Following the vaccination, NMAEs are common of which headache and myalgia comprised a considerable measure, although life-threatening unsolicited events are rare. NMAEs should be continuously monitored during the ongoing global COVID-19 vaccination program.

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Photobiomodulation for the Treatment of Primary Headache: Systematic Review of Randomized Clinical Trials

Life ◽

10.3390/life12010098 ◽

2022 ◽

Vol 12 (1) ◽

pp. 98

Author(s):

Andréa Oliver Gomes ◽

Ana Luiza Cabrera Martimbianco ◽

Aldo Brugnera Junior ◽

Anna Carolina Ratto Tempestini Horliana ◽

Tamiris da Silva ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Adjuvant Treatment ◽

Randomized Clinical Trials ◽

Primary Headache ◽

Risk Of Bias ◽

Cochrane Library ◽

Sham Treatment ◽

Methodological Assessment ◽

Grade Approach

The purpose of this study was to evaluate the efficacy and safety of photobiomodulation as an adjuvant treatment for primary headache. A systematic review of randomized clinical trials was performed. For such, electronic searches were performed in the MEDLINE, Embase, Cochrane Library, LILACS, PEDro, PsycInfo, Clinicaltrials.gov., and WHO/ICTRP databases, with no restrictions imposed regarding language or year of publication. We included studies that assessed any photobiomodulation therapy as an adjuvant treatment for primary headache compared to sham treatment, no treatment, or another intervention. The methodological assessment was conducted using the Cochrane Risk of Bias tool. The certainty of the evidence was classified using the GRADE approach. Four randomized clinical trials were included. Most of the included studies had an overall high risk of bias. Compared to sham treatment, photobiomodulation had a clinically important effect on pain in individuals with primary headache. Despite the benefits reported for other outcomes, the estimates were imprecise, and the certainty of the evidence was graded as low. These findings are considered insufficient to support the use of photobiomodulation in the treatment of primary headache. Randomized clinical trials, with higher methodological quality, are needed to enhance the reliability of the estimated effects.

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Efficacy and Safety of Blinatumomab for Relapsed or Refractory Pediatric ALL Patients: A Systematic Review

Blood ◽

10.1182/blood-2020-137576 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 22-23

Author(s):

Anam Khan ◽

Atif Irfan Khan ◽

Sana Irfan Khan ◽

Sobia Aamir ◽

Usman Ali Akbar ◽

...

Keyword(s):

Systematic Review ◽

Overall Survival ◽

Clinical Trials ◽

T Cells ◽

Complete Remission ◽

Adverse Outcomes ◽

Term Survival ◽

Paediatric Patients ◽

Grade 3

Background Most children with Acute Lymphoblastic Leukaemia achieve complete remission and subsequent cure after chemotherapy. But, ALL relapse is the leading cause of treatment failure in paediatric patients, causing long term survival to below. Chemotherapy along with targeted therapies have been explored in relapsed/refractory ALL (R/R ALL) patients. One such targeted therapy is Blinatumomab (Blin), a bi-specific T-cell engagers (BiTEs) antibody, it binds to CD3 receptors on T-cells and CD19 receptors on B-cells thereby re-directing T-cells to exert their cytotoxic effect on malignant as well as non-malignant B-cells. Blin was approved by FDA in March 2018 for the treatment of B-cell precursor ALL in first or second complete remission with minimal residual disease (MRD) ≥0.1%. This approval was based on BLAST trial conducted on ≥18-year-old ALL patients. The drug has been studied in children (1-18 years) with five clinical trials exclusively in children of which two have reported their results and three are ongoing. In this systematic review, we evaluated the safety and efficacy of Blin as a monotherapy in paediatric R/R ALL patients. Material/Methods We performed a search on PubMed, Embase, Clinical Trials, Web of Science and Cochrane. We used Mesh Terms "ALL" and "Blinatumomab" without any filters. After screening of 1199 articles, 5 clinical trial, 3 retrospective studies and 1 case series were included. These studies included only paediatric patients (<18yrs) evaluating the role of Blin as monotherapy in R/R ALL. We followed the PRISMA guidelines for literature search and selection of studies RESULTS: A total number of patients who received Blin was 320, all were <18 years. The preceding treatment regimens included multi-agent chemotherapy with or without hematopoietic stem cell transplant (HSCT). Five studies included only those patients with more than ≥5% bone marrow blasts. Though many combination monoclonal antibody therapies are available, we included only patients given Blin as monotherapy. Blin therapy was a 4 weeks continuous infusion at a dosage of 5 or 15μg/m2/day followed by 2 weeks of treatment-free interval as one cycle, in the studies, the number of treatment cycles ranged from 1-18. A median follow up in the studies ranged from 6 months to 5 years. Overall, complete response (CR) was found to be 58% (n=184) ranging between 31% to 100%. Following CR with Blin relapse rate was 40% (n=66). The overall median survival ranged from 4.3 to 22 months amongst 5 of the nine studies, while it was reported to be 80% (n=9) survival at the end of 12 months by Elitzur et al and 33.3% (n=3) at the end of two cycles of blin by Schlegel, P et al, the remaining two studies did not mention the duration of overall survival. The cumulative hematologic adverse outcomes of ≥grade 3 amongst the studies reported were neutropenia 22% (n=70), Anemia 27.7%(n=55), thrombocytopenia as reported in four studies was 21.5% (n=30). Fuster J et al. reported a cumulative non-hematologic adverse outcome of 40%(n=6) while other studies reported ≥ grade 3 non-hematologic adverse outcomes with increased liver enzymes, neurologic problems and fever to be most common. Cumulative cytokine release syndrome was reported as 4.7% (n=14) in 6 out of 9 studies. Elitzur et al. reported no non-hematologic adverse effect. We found total cumulative death reported as 17% of cases (n=34). Conclusion Blinatumomab use for R/R ALL paediatric patients treatment showed promising outcomes with more than half of the patients achieving CR. Overall survival has been good with median patient surviving disease-free between 4 to 22 months at large. Though, low mortality indicated long term survival, a high relapse rate points that Blin with combination therapy may show better outcomes. Fifteen ongoing clinical trials are testing Blin currently, three of which are on paediatric R/R ALL group. One trial is testing a combination of Blin and pembrolizumab. The results of these trials will further provide information on its effectiveness in combination therapy. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.:Honoraria, Research Funding, Speakers Bureau.

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Stem Cells in Clinical Trials for Pelvic Floor Disorders: a Systematic Literature Review

Reproductive Sciences ◽

10.1007/s43032-021-00745-6 ◽

2021 ◽

Author(s):

Stefano Manodoro ◽

Matteo Frigerio ◽

Marta Barba ◽

Sara Bosio ◽

Luigi Antonio de Vitis ◽

...

Keyword(s):

Clinical Trials ◽

Stem Cell ◽

Pelvic Floor ◽

Pelvic Floor Disorders ◽

Treatment Options ◽

Current Treatment ◽

Cochrane Library ◽

Safe Procedure ◽

Alternative Treatment Strategy ◽

Beneficial Impact

AbstractPelvic floor disorders (PFDs) include a series of conditions that can be poorly tolerated, negatively affecting the quality of life. Current treatment options show unsatisfactory results and new ones are therefore needed. Stem cell (SC) therapy might be an alternative treatment strategy. This systematic review aims to define the state of art of SC therapy for PFDs in clinical trials, by systematically reviewing the available evidence. A systematic search strategy was conducted up to November 7, 2020, in PubMed, Scopus, Cochrane Library, and ISI Web of Science. Preclinical studies on animal models were not considered. Studies were included when the patients were affected by any PFDs and cells were isolated, cultured, and characterized as SC. The study protocol was registered in PROSPERO (CRD42020216551). A total of 11 prospective clinical studies were included in the final assessment, specifically 7 single-arm studies dealing with SC therapy for stress urinary incontinence and 4 with anal incontinence. Among the latter, there were two prospective, single-arm studies and two randomized controlled trials. No papers concerning the use of SC for prolapse repair were retrieved. Due to the great heterogeneity, data pooling was not possible. Stem cell injection resulted in a safe procedure, with few mild adverse side effects, mostly related to harvesting sites. However, a clear beneficial impact of SC treatment for the treatment of pelvic floor disorders could not be demonstrated. Further larger targeted studies with control arms are needed before any conclusions can be made.

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How do community advisory boards fulfil their ethical role in HIV clinical trials? A protocol for a systematic review of qualitative evidence

BMJ Open ◽

10.1136/bmjopen-2019-035368 ◽

2020 ◽

Vol 10 (4) ◽

pp. e035368

Author(s):

Godwin Pancras ◽

Maryam Amour ◽

Tosi Mwakyandile ◽

Baraka Morris ◽

Bruno F Sunguya ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Grey Literature ◽

Cochrane Library ◽

Global Health Research ◽

Advisory Boards ◽

Qualitative Evidence ◽

Ethical Role ◽

Hiv Clinical Trials ◽

Community Advisory Boards

IntroductionCommunity advisory boards (CABs) continue to gain wide use and acceptance in global health research including in HIV clinical trials. They provide means through which community concerns regarding the trial can be considered by the research team, and provide an important platform of communication between the researchers and the community about study goals. Therefore, this systematic review protocol will guide the review of qualitative evidence on the ethical roles of CABs in HIV clinical trials based on the three fundamental ethical principles: respect for the person, beneficence and justice.Methods and analysisThis systematic review of qualitative evidence will involve searching four medical databases: PubMed, ScienceDirect, CINAHL and Cochrane Library. Additionally, other relevant evidence will be obtained through hand searching and grey literature. Searches will be limited to studies published in the English language from 1989 (the year that CABs were first established in HIV clinical trials) to 2019. Articles searched will be screened by two independent authors based on inclusion and exclusion criteria. Included articles will be appraised for quality using the Critical Appraisal Skills Programme checklist and followed by qualitative data extraction. Findings will be analysed based on the meta-aggregative approach with the aid of EPPI-Reviewer 4 web-based software.Ethics and disseminationEthical approval does not apply to this review. Data will be disseminated through scientific conferences and peer-reviewed journals to inform policies and stake-holders about the ethical role of CABs.PROSPERO registration numberCRD42019133787.

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