scholarly journals Non-randomised evaluations of strategies to increase participant retention in randomised controlled trials: a systematic review

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Adel Elfeky ◽  
Katie Gillies ◽  
Heidi Gardner ◽  
Cynthia Fraser ◽  
Timothy Ishaku ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Response Rate ◽  
Postal Questionnaire ◽  
Risk Of Bias ◽  
Randomised Trials ◽  
Questionnaire Response ◽  
Retention Strategies ◽  
Participant Retention

Abstract Background Retention of participants is essential to ensure the statistical power and internal validity of clinical trials. Poor participant retention reduces power and can bias the estimates of intervention effect. There is sparse evidence from randomised comparisons of effective strategies to retain participants in randomised trials. Currently, non-randomised evaluations of trial retention interventions embedded in host clinical trials are rejected from the Cochrane review of strategies to improve retention because it only included randomised evaluations. However, the systematic assessment of non-randomised evaluations may inform trialists’ decision-making about retention methods that have been evaluated in a trial context.Therefore, we performed a systematic review to synthesise evidence from non-randomised evaluations of retention strategies in order to supplement existing randomised trial evidence. Methods We searched MEDLINE, EMBASE, and Cochrane CENTRAL from 2007 to October 2017. Two reviewers independently screened abstracts and full-text articles for non-randomised studies that compared two or more strategies to increase participant retention in randomised trials. The retention trials had to be nested in real ‘host’ trials ( including feasibility studies) but not hypothetical trials. Two investigators independently rated the risk of bias of included studies using the ROBINS-I tool and determined the certainty of evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework. Results Fourteen non-randomised studies of retention were included in this review. Most retention strategies (in 10 studies) aimed to increase questionnaire response rate. Favourable strategies for increasing questionnaire response rate were telephone follow-up compared to postal questionnaire completion, online questionnaire follow-up compared to postal questionnaire, shortened version of questionnaires versus longer questionnaires, electronically transferred monetary incentives compared to cash incentives, cash compared with no incentive and reminders to non-responders (telephone or text messaging). However, each retention strategy was evaluated in a single observational study. This, together with risk of bias concerns, meant that the overall GRADE certainty was low or very low for all included studies. Conclusions This systematic review provides low or very low certainty evidence on the effectiveness of retention strategies evaluated in non-randomised studies. Some strategies need further evaluation to provide confidence around the size and direction of the underlying effect.

scholarly journals Does pre-notification increase questionnaire response rates: a nested randomised control trial

2021 ◽  
Author(s):  
Benjamin Woolf ◽  
Phil Edwards
Keyword(s):  
Systematic Review ◽  
Response Rates ◽  
Risk Of Bias ◽  
Randomised Control Trial ◽  
Questionnaire Response ◽  
Potential Study ◽  
Study Results ◽  
Study Participants ◽  
Unclear Risk

AbstractBackgroundStudy results can be badly affected by non-response. One way to potentially reduce non-response is by sending potential study participants advance communication. During the update of a systematic review examining the effect of pre-notification on response rates, a number of study authors needed to be contacted for further information.ObjectivesTo conduct an RCT to investigate the effect of pre-notification, nested within the request for further information for a systematic review.MethodsStudy authors included in the systematic review, whose studies were at unclear risk of bias, and who were contactable, were randomly sent or not set a pre-notification email prior to being sent the request for further information email.ResultsAt the end of follow up, 14/33 (42.4%) authors in the pre-notification condition had returned responses to the questionnaire, and 18/42 (42.9%). There was not evidence of a difference between these groups.ConclusionsThis study’s results do not support the hypothesis that pre-notification does increase response from participants.

scholarly journals Artificial intelligence versus clinicians: systematic review of design, reporting standards, and claims of deep learning studies

BMJ ◽  
2020 ◽  
pp. m689 ◽  
Author(s):  
Myura Nagendran ◽  
Yang Chen ◽  
Christopher A Lovejoy ◽  
Anthony C Gordon ◽  
Matthieu Komorowski ◽  
...  
Keyword(s):  
Artificial Intelligence ◽  
Systematic Review ◽  
Clinical Trials ◽  
Deep Learning ◽  
Medical Imaging ◽  
Prediction Model ◽  
Real World ◽  
Risk Of Bias ◽  
Reporting Standards ◽  
Randomised Trials

Abstract Objective To systematically examine the design, reporting standards, risk of bias, and claims of studies comparing the performance of diagnostic deep learning algorithms for medical imaging with that of expert clinicians. Design Systematic review. Data sources Medline, Embase, Cochrane Central Register of Controlled Trials, and the World Health Organization trial registry from 2010 to June 2019. Eligibility criteria for selecting studies Randomised trial registrations and non-randomised studies comparing the performance of a deep learning algorithm in medical imaging with a contemporary group of one or more expert clinicians. Medical imaging has seen a growing interest in deep learning research. The main distinguishing feature of convolutional neural networks (CNNs) in deep learning is that when CNNs are fed with raw data, they develop their own representations needed for pattern recognition. The algorithm learns for itself the features of an image that are important for classification rather than being told by humans which features to use. The selected studies aimed to use medical imaging for predicting absolute risk of existing disease or classification into diagnostic groups (eg, disease or non-disease). For example, raw chest radiographs tagged with a label such as pneumothorax or no pneumothorax and the CNN learning which pixel patterns suggest pneumothorax. Review methods Adherence to reporting standards was assessed by using CONSORT (consolidated standards of reporting trials) for randomised studies and TRIPOD (transparent reporting of a multivariable prediction model for individual prognosis or diagnosis) for non-randomised studies. Risk of bias was assessed by using the Cochrane risk of bias tool for randomised studies and PROBAST (prediction model risk of bias assessment tool) for non-randomised studies. Results Only 10 records were found for deep learning randomised clinical trials, two of which have been published (with low risk of bias, except for lack of blinding, and high adherence to reporting standards) and eight are ongoing. Of 81 non-randomised clinical trials identified, only nine were prospective and just six were tested in a real world clinical setting. The median number of experts in the comparator group was only four (interquartile range 2-9). Full access to all datasets and code was severely limited (unavailable in 95% and 93% of studies, respectively). The overall risk of bias was high in 58 of 81 studies and adherence to reporting standards was suboptimal (<50% adherence for 12 of 29 TRIPOD items). 61 of 81 studies stated in their abstract that performance of artificial intelligence was at least comparable to (or better than) that of clinicians. Only 31 of 81 studies (38%) stated that further prospective studies or trials were required. Conclusions Few prospective deep learning studies and randomised trials exist in medical imaging. Most non-randomised trials are not prospective, are at high risk of bias, and deviate from existing reporting standards. Data and code availability are lacking in most studies, and human comparator groups are often small. Future studies should diminish risk of bias, enhance real world clinical relevance, improve reporting and transparency, and appropriately temper conclusions. Study registration PROSPERO CRD42019123605.

scholarly journals Dialysis and plasmapheresis for schizophrenia: a systematic review

2020 ◽  
Vol 50 (8) ◽  
pp. 1233-1240 ◽  
Author(s):  
Emily R. Cox ◽  
Katie F. M. Marwick ◽  
Robert W. Hunter ◽  
Josef Priller ◽  
Stephen M. Lawrie
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
High Risk ◽  
Detrimental Effect ◽  
Immune Dysfunction ◽  
Risk Of Bias ◽  
Randomised Trials ◽  
Inclusion Criteria ◽  
High Quality ◽  
Double Blinded

AbstractIncreasing evidence suggests that circulating factors and immune dysfunction may contribute to the pathogenesis of schizophrenia. In particular, proinflammatory cytokines, complement and autoantibodies against CNS epitopes have recently been associated with psychosis. Related concepts in previous decades led to several clinical trials of dialysis and plasmapheresis as treatments for schizophrenia. These trials may have relevance for the current understanding of schizophrenia. We aimed to identify whether dialysis or plasmapheresis are beneficial interventions in schizophrenia. We conducted a systematic search in major electronic databases for high-quality studies (double-blinded randomised trials with sham controls) applying either haemodialysis or plasmapheresis as an intervention in patients with schizophrenia, published in English from the start of records until September 2018. We found nine studies meeting inclusion criteria, reporting on 105 patients in total who received either sham or active intervention. One out of eight studies reported a beneficial effect of haemodialysis on schizophrenia, one a detrimental effect and six no effect. The sole trial of plasmapheresis found it to be ineffective. Adverse events were reported in 23% of patients. Studies were at unclear or high risk of bias. It is unlikely that haemodialysis is a beneficial treatment in schizophrenia, although the studies were of small size and could not consider potential subgroups. Plasmapheresis was only addressed by one study and warrants further exploration as a treatment modality in schizophrenia.

scholarly journals Therapeutic efficacy of alternative primaquine regimens to standard treatment in preventing relapses by Plasmodium vivax: A systematic review and meta-analysis

2015 ◽  
pp. 183-191 ◽  
Author(s):  
Lina Marcela Zuluaga Idarraga ◽  
Maria Eulalia Tamayo Perez ◽  
Daniel Camilo Aguirre Acevedo
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Relative Risk ◽  
Fixed Effects ◽  
Standard Treatment ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Efficacy And Safety ◽  
Standard Regimen

Objective: To compare efficacy and safety of primaquine regimens currently used to prevent relapses by P. vivax. Methods: A systematic review was carried out to identify clinical trials evaluating efficacy and safety to prevent malaria recurrences by P. vivax of primaquine regimen 0.5 mg / kg / day for 7 or 14 days compared to standard regimen of 0.25 mg/kg/day for 14 days. Efficacy of primaquine according to cumulative incidence of recurrences after 28 days was determined. The overall relative risk with fixed-effects meta-analysis was estimated. Results: For the regimen 0.5 mg/kg/day/7 days were identified 7 studies, which showed an incidence of recurrence between 0% and 20% with follow-up 60-210 days; only 4 studies comparing with the standard regimen 0.25 mg/kg/day/14 days and no difference in recurrences between both regimens (RR= 0.977, 95% CI= 0.670 to 1.423) were found. 3 clinical trials using regimen 0.5 mg/kg/day/14 days with an incidence of recurrences between 1.8% and 18.0% during 330-365 days were identified; only one study comparing with the standard regimen (RR= 0.846, 95% CI= 0.484 to 1.477). High risk of bias and differences in handling of included studies were found. Conclusion: Available evidence is insufficient to determine whether currently PQ regimens used as alternative rather than standard treatment have better efficacy and safety in preventing relapse of P. vivax. Clinical trials are required to guide changes in treatment regimen of malaria vivax.

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

2018 ◽  
Vol 19 (1) ◽  
pp. 41-49 ◽  
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.

Exercise interventions in lateral elbow tendinopathy have better outcomes than passive interventions, but the effects are small: a systematic review and meta-analysis of 2123 subjects in 30 trials

2020 ◽  
pp. bjsports-2020-102525
Author(s):  
Stefanos Karanasios ◽  
Vasileios Korakakis ◽  
Rod Whiteley ◽  
Ioannis Vasilogeorgis ◽  
Sarah Woodbridge ◽  
...  
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Short Term ◽  
Lateral Elbow ◽  
Long Term Follow Up ◽  
Wait And See ◽  
Lateral Elbow Tendinopathy

ObjectiveTo evaluate the effectiveness of exercise compared with other conservative interventions in the management of lateral elbow tendinopathy (LET) on pain and function.DesignSystematic review and meta-analysis.MethodsWe used the Cochrane risk-of-bias tool 2 for randomised controlled trials (RCTs) to assess risk of bias and the Grading of Recommendations Assessment, Development and Evaluation methodology to grade the certainty of evidence. Self-perceived improvement, pain intensity, pain-free grip strength (PFGS) and elbow disability were used as primary outcome measures.Eligibility criteriaRCTs assessing the effectiveness of exercise alone or as an additive intervention compared with passive interventions, wait-and-see or injections in patients with LET.Results30 RCTs (2123 participants, 5 comparator interventions) were identified. Exercise outperformed (low certainty) corticosteroid injections in all outcomes at all time points except short-term pain reduction. Clinically significant differences were found in PFGS at short-term (mean difference (MD): 12.15, (95% CI) 1.69 to 22.6), mid-term (MD: 22.45, 95% CI 3.63 to 41.3) and long-term follow-up (MD: 18, 95% CI 11.17 to 24.84). Statistically significant differences (very low certainty) for exercise compared with wait-and-see were found only in self-perceived improvement at short-term, pain reduction and elbow disability at short-term and long-term follow-up. Substantial heterogeneity in descriptions of equipment, load, duration and frequency of exercise programmes were evident.ConclusionsLow and very low certainty evidence suggests exercise is effective compared with passive interventions with or without invasive treatment in LET, but the effect is small.PROSPERO registration numberCRD42018082703.

scholarly journals Effects of open-label placebos in clinical trials: a systematic review and meta-analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Melina von Wernsdorff ◽  
Martin Loef ◽  
Brunna Tuschen-Caffier ◽  
Stefan Schmidt
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Medical Condition ◽  
Data Extraction ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Open Label ◽  
Cancer Related Fatigue ◽  
Promising Treatment ◽  
Irritable Bowel

AbstractOpen-label placebos (OLPs) are placebos without deception in the sense that patients know that they are receiving a placebo. The objective of our study is to systematically review and analyze the effect of OLPs in comparison to no treatment in clinical trials. A systematic literature search was carried out in February 2020. Randomized controlled trials of any medical condition or mental disorder comparing OLPs to no treatment were included. Data extraction and risk of bias rating were independently assessed. 1246 records were screened and thirteen studies were included into the systematic review. Eleven trials were eligible for meta-analysis. These trials assessed effects of OLPs on back pain, cancer-related fatigue, attention deficit hyperactivity disorder, allergic rhinitis, major depression, irritable bowel syndrome and menopausal hot flushes. Risk of bias was moderate among all studies. We found a significant overall effect (standardized mean difference = 0.72, 95% Cl 0.39–1.05, p < 0.0001, I2 = 76%) of OLP. Thus, OLPs appear to be a promising treatment in different conditions but the respective research is in its infancy. More research is needed, especially with respect to different medical and mental disorders and instructions accompanying the OLP administration as well as the role of expectations and mindsets.

scholarly journals Clinical effectiveness of convalescent plasma in hospitalized patients with COVID-19: a systematic review and meta-analysis

2021 ◽  
Vol 15 ◽  
pp. 175346662110280
Author(s):  
Roberto Ariel Abeldaño Zuñiga ◽  
Ruth Ana María González-Villoria ◽  
María Vanesa Elizondo ◽  
Anel Yaneli Nicolás Osorio ◽  
David Gómez Martínez ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Clinical Improvement ◽  
Data Extraction ◽  
Meta Analysis ◽  
Clinical Effectiveness ◽  
Risk Of Bias ◽  
Hospitalized Patients ◽  
Low Risk ◽  
Controlled Clinical Trials

Aims: Given the variability of previously reported results, this systematic review aims to determine the clinical effectiveness of convalescent plasma employed in the treatment of hospitalized patients diagnosed with COVID-19. Methods: We conducted a systematic review of controlled clinical trials assessing treatment with convalescent plasma for hospitalized patients diagnosed with SARS-CoV-2 infection. The outcomes were mortality, clinical improvement, and ventilation requirement. Results: A total of 51 studies were retrieved from the databases. Five articles were finally included in the data extraction and qualitative and quantitative synthesis of results. The overall risk of bias in the reviewed articles was established at low-risk only in two trials. The meta-analysis suggests that there is no benefit of convalescent plasma compared with standard care or placebo in reducing the overall mortality and the ventilation requirement. However, there could be a benefit for the clinical improvement in patients treated with plasma. Conclusion: Current results led to assume that the convalescent plasma transfusion cannot reduce the mortality or ventilation requirement in hospitalized patients diagnosed with SARS-CoV-2 infection. More controlled clinical trials conducted with methodologies that ensure a low risk of bias are still needed. The reviews of this paper are available via the supplemental material section.

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

Cancers ◽  
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.

Sign in / Sign up

Export Citation Format

Share Document