Reporting Both Unadjusted and Adjusted Estimates Is Essential to the Interpretation of Randomized Clinical Trial Results

Author(s):  
Robert S. Ware
Author(s):  
Ville N. Pimenoff ◽  
Miriam Elfström ◽  
Joakim Dillner

ABSTRACTBackgroundTransfusion of convalescent immune plasma (CP) is commonly used in epidemics. Several articles now describe clinical report data of CP for treatment of SARS-CoV-2-induced COVID-19 disease.MethodsA systematic literature review was conducted using the NCBI curated COVID-19 related open-resource literature database LitCovid to identify studies using CP as treatment for COVID-19 patients. We retrieved and curated all COVID-19 related patient and treatment characteristics from previously reported studies. A Poisson model was developed to evaluate the association between age of the patients, older age being the most common risk factor for COVID-19 mortality, and recovery time since CP treatment using data extracted from the literature.ResultsFrom 18,293 identified COVID-19 related articles, we included ten studies reporting results of CP treatment for COVID-19 from a total of 61 patients. Decreased symptoms of severe COVID-19 and clearance of SARS-CoV-2 RNA were the most direct observations. We found that patients over the age of sixty who received CP treatment for COVID-19 had a significantly prolonged recovery estimated by viral clearance (from 10 to 29 days since first dose of CP) compared to younger patients, who recovered from the infection in less than a week after receiving CP treatment.ConclusionsLimited published results on plasma transfusion treatment for COVID-19 disease with concomitant treatments suggest that CP therapy for COVID-19 is well tolerated and effective. First randomized clinical trial results, however, revealed no improvements in recovery time for elderly patients with severe COVID-19 between standard treatment alone and added with convalescent plasma. Accordingly, we argue that older patients may need a significantly longer time for recovery. Further randomized clinical trial data for COVID-19 with rigorous ethical standards is urgently needed.


2020 ◽  
Vol 3 (8) ◽  
pp. e2012469
Author(s):  
Muhammad Shahzeb Khan ◽  
Gregg C. Fonarow ◽  
Tim Friede ◽  
Noman Lateef ◽  
Safi U. Khan ◽  
...  

2018 ◽  
Vol 188 (2) ◽  
pp. 426-437 ◽  
Author(s):  
Jin-Liern Hong ◽  
Michael Webster-Clark ◽  
Michele Jonsson Funk ◽  
Til Stürmer ◽  
Sara E Dempster ◽  
...  

2020 ◽  
Vol 9 (15) ◽  
pp. 1043-1050
Author(s):  
Kristin M Sheffield ◽  
Nancy A Dreyer ◽  
James F Murray ◽  
Douglas E Faries ◽  
Megan N Klopchin

The FDA is preparing guidance about using real-world evidence (RWE) to support decisions about product effectiveness. Several ongoing efforts aim to replicate randomized clinical trial (RCT) results using RWE with the intent of identifying circumstances and methods that provide valid evidence of drug effects. Lack of agreement may not be due to faulty methods but rather to the challenges with emulating RCTs, differences in healthcare settings and patient populations, differences in effect measures and data analysis, bias, and/or the efficacy–effectiveness gap. In fact, for some decisions, RWE may lead to better understanding of how treatments work in usual care settings than a more constrained view from RCTs. Efforts to reconcile the role and opportunities for generating complementary evidence from RWE and RCTs will advance regulatory science.


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