Mechanistic rationale of drugs, Primary endpoints, Geographical distribution of clinical trials against Severe acute respiratory syndrome-related coronavirus-2: A Systematic review
A significant number of clinical trials are ongoing against SARS-CoV-2, but only a small fraction focus on mortality, raising concerns about the relevance of many studies.
Where it sits
this study against the rest of the hgh (somatropin) corpusSummary and findings
This systematic review assessed ongoing clinical trials targeting SARS-CoV-2, focusing on various therapeutic interventions. A total of 829 studies were included, with 463 evaluating drug-based treatments. The review highlights a predominance of studies funded by federal and academic institutions, with limited focus on definitive outcomes like mortality.
Abstract
<h4>Objective</h4> To do a systematic review and critical appraisal of the ongoing clinical trials that are assessing various therapeutic interventions against SARS-CoV-2 with an aim to provide insight into the various interventions tested, clinical rationale, geographical distribution of the trials as well as the endpoints assessed in the studies. <h4>Design</h4> Rapid systematic review and critical appraisal of the ongoing clinical trials against SARS-CoV-2. <h4>Data sources</h4> ClinicalTrials.gov, World health organization (WHO) International Clinical Trials Registry Platform (ICTRP) and Cochrane COVID registry were assessed till May 11 th 2020. <h4>Study selection</h4> Studies on any intervention based randomized controlled trials (RCTs), prospective clinical studies on SARS-CoV-2 in patients ≥18 years of age. Studies on autopsy series, preclinical studies, diagnostic methods, mathematical modelling, epidemiology and health services research, pediatric populations were excluded. <h4>Data extraction</h4> The data was extracted by two authors independently into pre-defined forms based on the SPIRIT 2013 checklist. The data was extracted on various domains such as trial number, study title, abstract of the study, interventions assessed, sample size, phase of the study, study sponsor, primary endpoint assessed and country of study. <h4>Results</h4> The search resulted in 3242 ongoing studies of which 829 studies were included. There are 134 different drug-based interventions being assessed in 463 clinical trials as treatment options. Seventy-two studies assessed preventive options of which 53 are drug-based prophylaxis and 19 assessed vaccines. Herbal medicines are being assessed in 79 studies; convalescent plasma therapy in 56 studies; stem cell-based interventions in 42 studies; anesthesia-based interventions in 31 studies, machine-based interventions in 24 studies, mental health-based interventions in18 studies, rehabilitation-based interventions in 12 studies and miscellaneous interventions in 32 studies. China accounts for 35% of all ongoing clinical studies followed by USA 23%, France 7%, Spain 3.3%,Canada 2%, multi-country studies account only for 1.5% (13) and other countries together account for 28%.Amongst the 463 studies assessing drug-based treatment options, studies that are funded by federal and academic institutions are 79.6%, pharmaceutical company funded studies are 15.11% and no funding information is available in 5.10%. The definitive outcomes like mortality are being assessed as primary outcome in 22.8% of the studies only and need for ventilator in 6.2% of the studies. Rest of the studies has primary outcomes such as clinical recovery (15.9%), viral clearance(17.4%), time to recovery (10.1%), oxygen improvement (5.6%), ICU admission (1.9%), lab and imaging(6.4%), adverse effects (5.3%) and symptom reduction(1.5%),no outcome reported(6.2%) which account for 71% of the studies. Amongst the pharmaceutical company funded drug-based studies, only 20% of the studies had mortality as the primary outcome. Only 5.5% of the ongoing clinical trials are specifically designed to assess the most vulnerable population like elderly, patients with comorbidities and cancer. The most common intervention being tested against COVID-19 are antimalarial medications with 105 clinical studies. Hydroxychloroquine is the most common drug being tested with 83 ongoing studies. <h4>Conclusion</h4> Multiple intervention based clinical studies against SARS-CoV-2 are being performed throughout the world with a high concentration of clinical trials in the developed world. There is a high concern that most of the studies maybe repetitive; elderly and patients with comorbidities are being underrepresented; definite endpoints like mortality are being assessed in only one-fifth of the studies.
Background
This paper addresses the clinical question of which therapeutic interventions are being tested against SARS-CoV-2. Prior knowledge indicated a surge in clinical trials since the onset of the pandemic, but the effectiveness and focus of these trials remained unclear. Understanding the landscape of ongoing research is crucial for identifying gaps and ensuring that vulnerable populations are adequately represented.
Methods
This study employed a rapid systematic review design, analyzing data from ClinicalTrials.gov, WHO ICTRP, and Cochrane COVID registry up to May 11, 2020. The selection criteria included randomized controlled trials and prospective clinical studies involving patients aged 18 and older, while excluding studies on autopsy series, preclinical research, and pediatric populations. Data extraction was performed independently by two authors using predefined forms.
Results
The review identified 3242 ongoing studies, with 829 studies meeting inclusion criteria. Among these, 463 studies focused on drug-based treatment options. Primary outcomes varied, with only 22.8% assessing mortality, while 15.9% focused on clinical recovery and 17.4% on viral clearance.
Interpretation
The findings suggest a significant focus on drug-based interventions, particularly antimalarial medications. However, the low percentage of studies assessing mortality raises concerns about the clinical relevance of these trials. The predominance of federal and academic funding may also influence the focus and outcomes of the research, indicating a need for more diverse funding sources and endpoints.
Key findings
- 3242 ongoing studies identified, n=829 included.
- 463 clinical trials assessed drug-based treatment options.
- 22.8% of studies assess mortality as a primary outcome.
- Only 5.5% of trials target vulnerable populations such as the elderly and patients with comorbidities.
- Hydroxychloroquine is the most common drug being tested with 83 ongoing studies.
Limitations
- Only 22.8% of studies assess mortality as a primary outcome.
- 5.5% of trials target vulnerable populations like the elderly.
- High concentration of studies in developed countries may limit generalizability.
- Potential repetitiveness in ongoing studies.
- Limited funding transparency with 5.10% of studies lacking funding information.