scholarly journals Known unknowns and unknown unknowns – An introduction to research on harms

2021 ◽  
Author(s):  
Riaz Qureshi ◽  
Evan Mayo-Wilson ◽  
Tianjing Li

ObjectiveMost systematic reviews of interventions focus on potential benefits. Common methods and assumptions that are appropriate for assessing benefits can be inappropriate for harms. This paper provides a primer on researching harms, particularly in systematic reviews. Study Design and SettingNarrative review to describe challenges with assessing harm.ResultsSystematic reviewers and investigators for primary studies should be familiar with various terminologies used to describe and classify harms across settings and study reports. Some classification systems facilitate grouping harms for analysis, which has both advantages and limitations for causal inference. Published reports of clinical trials include limited information about harms, so systematic reviewers should not depend on these studies and journal articles to reach conclusions about harms. Visualizations might improve communication of multiple dimensions of harms such as severity, relatedness, and timing.ConclusionThe terminology, classification, detection, collection, and reporting of harms create unique challenges that take time, expertise, and resources to navigate in both primary studies and evidence syntheses. Systematic reviewers might reach incorrect conclusions if they focus on evidence about harms found in published reports of randomized trials of a particular health problem. Systematic reviews could be improved through better identification and reporting of harms in primary studies and through better training and uptake of appropriate methods for synthesizing evidence about harms.

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Anette Blümle ◽  
Katharina Wollmann ◽  
Karin Bischoff ◽  
Philipp Kapp ◽  
Szimonetta Lohner ◽  
...  

Abstract Background Healthcare decisions are ideally based on clinical trial results, published in study registries, as journal articles or summarized in secondary research articles. In this research project, we investigated the impact of academically and commercially sponsored clinical trials on medical practice by measuring the proportion of trials published and cited by systematic reviews and clinical guidelines. Methods We examined 691 multicenter, randomized controlled trials that started in 2005 or later and were completed by the end of 2016. To determine whether sponsorship/funding and place of conduct influence a trial’s impact, we created four sub-cohorts of investigator initiated trials (IITs) and industry sponsored trials (ISTs): 120 IITs and 171 ISTs with German contribution compared to 200 IITs and 200 ISTs without German contribution. We balanced the groups for study phase and place of conduct. German IITs were funded by the German Research Foundation (DFG), the Federal Ministry of Education and Research (BMBF), or by another non-commercial research organization. All other trials were drawn from the German Clinical Trials Register or ClinicalTrials.gov. We investigated, to what extent study characteristics were associated with publication and impact using multivariable logistic regressions. Results For 80% of the 691 trials, results were published as result articles in a medical journal and/or study registry, 52% were cited by a systematic review, and 26% reached impact in a clinical guideline. Drug trials and larger trials were associated with a higher probability to be published and to have an impact than non-drug trials and smaller trials. Results of IITs were more often published as a journal article while results of ISTs were more often published in study registries. International ISTs less often gained impact by inclusion in systematic reviews or guidelines than IITs. Conclusion An encouraging high proportion of the clinical trials were published, and a considerable proportion gained impact on clinical practice. However, there is still room for improvement. For publishing study results, study registries have become an alternative or complement to journal articles, especially for ISTs. IITs funded by governmental bodies in Germany reached an impact that is comparable to international IITs and ISTs.


2020 ◽  
Author(s):  
Anette Blümle ◽  
Katharina Wollmann ◽  
Karin Bischoff ◽  
Szimonetta Lohner ◽  
Edris Nury ◽  
...  

Abstract BackgroundDecisions in healthcare are ideally made on basis of the results of clinical trials, published in study registries, as primary journal articles or summarized in secondary research articles. It is still unclear, whether and to what extent public and commercial expenses invested in clinical trials pays out in a way that their findings have an impact on publication output and medical practice.MethodsThe aim of this project was to examine the lifecycle of clinical trials from their registration to their publication and citation in secondary research articles by determining the proportion of trials that were published and were included in systematic review and clinical guidelines. We set-up a cohort of randomized controlled trials (n=691). We created and compared four sub-cohorts of investigator initiated trials (IITs) and industry sponsor trials (ISTs) with and without German contribution. For each trial, we searched for corresponding publications and citing systematic reviews and clinical guidelines.Additionally, we investigated what study characteristics are associated with publication and impact by using multivariable logistic regressions. ResultsOf the 691 trials, 576 (83%) were published as method article or result article in a medical journal and/or the trial results were made available in study registries; results were available for 555 (80%) of the trials. More than half (52%) of the trials were cited by a systematic review and about a quarter (26%) reached impact in a clinical guideline. Drug trials and larger trials are associated with a higher probability to be published and to have an impact than non-drug trials and smaller trials. Results of IITs were more often published as journal article, results of ISTs more often in study registries. International ISTs gain less often impact by inclusion in systematic reviews or guidelines than publicly sponsored trials.ConclusionA considerable proportion of clinical trials investigated was published and had an impact on clinical practice, whereas the proportions depend on specific study characteristic. Study registries are an important alternative or complement to journal articles for publishing study results. There is still a need to improve the transfer of knowledge generated in clinical research into practice.


2019 ◽  
Vol 25 (15) ◽  
pp. 1783-1790 ◽  
Author(s):  
Rosario Pastor ◽  
Josep A. Tur

Background: Several drugs have been currently approved for the treatment of obesity. The pharmacokinetic of liraglutide, as well as the treatment of type 2 diabetes mellitus, have been widely described. Objective: To analyze the published systematic reviews on the use of liraglutide for the treatment of obesity. Methods: Systematic reviews were found out through MEDLINE searches, through EBSCO host and the Cochrane Library based on the following terms: "liraglutide" as major term and using the following Medical Subject Headings (MesH) terms: "obesity", "overweight", "weight loss". A total of 3 systematic reviews were finally included to be analyzed. Results: From the three systematic reviews selected, only two included the randomized clinical trials, while the third study reviewed both randomized and non-randomized clinical trials. Only one review performed statistical tests of heterogeneity and a meta-analysis, combining the results of individual studies. Another review showed the results of individual studies with odds ratio and confidence interval, but a second one just showed the means and confidence intervals. In all studies, weight loss was registered in persons treated with liraglutide in a dose dependent form, reaching a plateau at 3.0 mg dose, which was reached just in men. Most usual adverse events were gastrointestinal. Conclusion: More powerful and prospective studies are needed to assess all aspects related to liraglutide in the overweight and obesity treatment.


2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Jennifer Pillay ◽  
Aireen Wingert ◽  
Tara MacGregor ◽  
Michelle Gates ◽  
Ben Vandermeer ◽  
...  

Abstract Background We conducted systematic reviews on the benefits and harms of screening compared with no screening or alternative screening approaches for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) in non-pregnant sexually active individuals, and on the relative importance patients’ place on the relevant outcomes. Findings will inform recommendations by the Canadian Task Force on Preventive Health Care. Methods We searched five databases (to January 24, 2020), trial registries, conference proceedings, and reference lists for English and French literature published since 1996. Screening, study selection, and risk of bias assessments were independently undertaken by two reviewers, with consensus for final decisions. Data extraction was conducted by one reviewer and checked by another for accuracy and completeness. Meta-analysis was conducted where appropriate. We used the GRADE approach to rate the certainty of the evidence. The Task Force and content experts provided input on determining thresholds for important effect sizes and on interpretation of findings. Results Of 41 included studies, 17 and 11 reported on benefits and harms of screening, respectively, and 14 reported on patient preferences. Universal screening for CT in general populations 16 to 29 years of age, using population-based or opportunistic approaches achieving low screening rates, may make little-to-no difference for a female’s risk of pelvic inflammatory disease (PID) (2 RCTs, n=141,362; 0.3 more in 1000 [7.6 fewer to 11 more]) or ectopic pregnancy (1 RCT, n=15,459; 0.20 more per 1000 [2.2 fewer to 3.9 more]). It may also not make a difference for CT transmission (3 RCTs, n=41,709; 3 fewer per 1000 [11.5 fewer to 6.9 more]). However, benefits may be achieved for reducing PID if screening rates are increased (2 trials, n=30,652; 5.7 fewer per 1000 [10.8 fewer to 1.1 more]), and for reducing CT and NG transmission when intensely screening high-prevalence female populations (2 trials, n=6127; 34.3 fewer per 1000 [4 to 58 fewer]; NNS 29 [17 to 250]). Evidence on infertility in females from CT screening and on transmission of NG in males and both sexes from screening for CT and NG is very uncertain. No evidence was found for cervicitis, chronic pelvic pain, or infertility in males from CT screening, or on any clinical outcomes from NG screening. Undergoing screening, or having a diagnosis of CT, may cause a small-to-moderate number of people to experience some degree of harm, mainly due to feelings of stigmatization and anxiety about future infertility risk. The number of individuals affected in the entire screening-eligible population is likely smaller. Screening may make little-to-no difference for general anxiety, self-esteem, or relationship break-up. Evidence on transmission from studies comparing home versus clinic screening is very uncertain. Four studies on patient preferences found that although utility values for the different consequences of CT and NG infections are probably quite similar, when considering the duration of the health state experiences, infertility and chronic pelvic pain are probably valued much more than PID, ectopic pregnancy, and cervicitis. How patients weigh the potential benefits versus harms of screening is very uncertain (1 survey, 10 qualitative studies); risks to reproductive health and transmission appear to be more important than the (often transient) psychosocial harms. Discussion Most of the evidence on screening for CT and/or NG offers low or very low certainty about the benefits and harms. Indirectness from use of comparison groups receiving some screening, incomplete outcome ascertainment, and use of outreach settings was a major contributor to uncertainty. Patient preferences indicate that the potential benefits from screening appear to outweigh the possible harms. Direct evidence about which screening strategies and intervals to use, which age to start and stop screening, and whether screening males in addition to females is necessary to prevent clinical outcomes is scarce, and further research in these areas would be informative. Apart from the evidence in this review, information on factors related to equity, acceptability, implementation, cost/resources, and feasibility will support recommendations made by the Task Force. Systematic review registration International Prospective Register of Systematic Reviews (PROSPERO), registration number CRD42018100733.


Logistics ◽  
2020 ◽  
Vol 4 (4) ◽  
pp. 27
Author(s):  
Abderahman Rejeb ◽  
John G. Keogh ◽  
Suhaiza Zailani ◽  
Horst Treiblmaier ◽  
Karim Rejeb

Blockchain technology has emerged as a promising technology with far-reaching implications for the food industry. The combination of immutability, enhanced visibility, transparency and data integrity provides numerous benefits that improve trust in extended food supply chains (FSCs). Blockchain can enhance traceability, enable more efficient recall and aids in risk reduction of counterfeits and other forms of illicit trade. Moreover, blockchain can enhance the integrity of credence claims such as sustainably sourced, organic or faith-based claims such as kosher or halal by integrating the authoritative source of the claim (e.g., the certification body or certification owner) into the blockchain to verify the claim integrity and reassure business customers and end consumers. Despite the promises and market hype, a comprehensive overview of the potential benefits and challenges of blockchain in FSCs is still missing. To bridge this knowledge gap, we present the findings from a systematic review and bibliometric analysis of sixty-one (61) journal articles and synthesize existing research. The main benefits of blockchain technology in FCSs are improved food traceability, enhanced collaboration, operational efficiencies and streamlined food trading processes. Potential challenges include technical, organizational and regulatory issues. We discuss the theoretical and practical implications of our research and present several ideas for future research.


2015 ◽  
Vol 18 (3) ◽  
pp. A12 ◽  
Author(s):  
N.J. Halfpenny ◽  
J.C. Thompson ◽  
J.M. Quigley ◽  
D.A. Scott

2016 ◽  
Vol 8 (2) ◽  
pp. 124-135 ◽  
Author(s):  
Mi-Ok Kim ◽  
Xia Wang ◽  
Chunyan Liu ◽  
Kathleen Dorris ◽  
Maryam Fouladi ◽  
...  

2019 ◽  
pp. 331-340
Author(s):  
Susan Churchill ◽  
◽  
Kayla Deru ◽  
Lindell K. Weaver ◽  
Steffanie H. Wilson ◽  
...  

Safety monitoring and successful blinding are important features of randomized, blinded clinical trials. We report chamber- and protocol-related adverse events (AEs) for participants enrolled in two randomized, double-blind clinical trials of hyperbaric oxygen (HBO2) for persistent post-concussive symptoms clinicaltrials.gov identifiers NCT01306968, HOPPS, and NCT01611194, BIMA), as well as the success of maintaining the blind with a low-pressure sham control arm. In both studies, participants were randomized to receive HBO2 (1.5 atmospheres absolute, >99% oxygen) or sham chamber sessions (1.2 atmospheres absolute, room air). In 143 participants undergoing 4,245 chamber sessions, chamber-related adverse events were rare (1.1% in the HOPPS study, 2.2% in the BIMA study). Minor, non-limiting barotrauma was the most frequently reported. Rarely, some participants experienced headache with chamber sessions. No serious adverse events were associated with chamber sessions. An allocation questionnaire completed after intervention revealed that the sham control arm adequately protected the blind in both trials. Participants based allocation assumptions on symptom improvement or lack of symptom improvement and could not discern intervention arm by pressure, smell, taste, or gas flow.


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