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1.
PLoS One ; 17(3): e0264427, 2022.
Article in English | MEDLINE | ID: covidwho-1731598

ABSTRACT

BACKGROUND: Conducting high quality investigator-initiated trials (IITs) is challenging and costly. The costs of investigational medicinal products (IMPs) in IITs and the role of hospital pharmacies in the planning of IITs are unclear. We conducted a mixed-methods study to compare planned and actual costs of IMPs in Swiss IITs, to examine potential reasons for differences, and to gather stakeholder views about hospital services for IITs. METHODS: We included all IITs with IMP services from the Basel hospital pharmacy invoiced between January 2014 and June 2020 (n = 24). We documented trial and IMP characteristics including planned and actual IMP costs. Our working definition for a substantial cost difference was that the actual IMP costs were more than 10% higher than the planned IMP costs in a trial. We conducted semi-structured interviews with investigators, clinical trials unit and hospital pharmacy staff, and qualitatively analyzed transcribed interviews. RESULTS: For 13 IITs we observed no differences between planned and actual costs of IMPs (median, 11'000 US$; interquartile range [IQR], 8'882-16'302 US$), but for 11 IITs we found cost increases from a median of 11'000 US$ (IQR, 8'922-36'166 US$) to a median over 28'000 US$ (IQR, 13'004-49'777 US$). All multicenter trials and 10 of 11 IITs with patients experienced substantial cost differences. From the interviews we identified four main themes: 1) Patient recruitment and organizational problems were identified as main reasons for cost differences, 2) higher actual IMP costs were bearable for most investigators, 3) IMP services for IITs were not a priority for the hospital pharmacy, and 4) closer collaboration between clinical trial unit and hospital pharmacy staff, and sufficient staff for IITs at the hospital pharmacy could improve IMP services. CONCLUSIONS: Multicenter IITs enrolling patients are particularly at risk for higher IMP costs than planned. These trials are more difficult to plan and logistically challenging, which leads to delays and expiring IMP shelf-lives. IMP services of hospital pharmacies are important for IITs in Switzerland, but need to be further developed.


Subject(s)
Pharmacies , Pharmacy Service, Hospital , Humans , Inosine Monophosphate , Organizations , Research Personnel
2.
Clin Infect Dis ; 2022 Mar 02.
Article in English | MEDLINE | ID: covidwho-1722275

ABSTRACT

BACKGROUND: BNT162b2 by Pfizer-BioNTech and mRNA-1273 by Moderna are the most commonly used vaccines to prevent SARS-CoV-2 infections. Head-to-head comparison of the efficacy of these vaccines in immunocompromised patients is lacking. METHODS: Parallel, two-arm (allocation 1:1), open-label, non-inferiority randomised clinical trial nested into the Swiss HIV Cohort Study and the Swiss Transplant Cohort Study. Patients living with HIV (PLWH) or solid organ transplant recipients (SOTR; i.e. lung and kidney) from these cohorts were randomised to mRNA-1273 or BNT162b2. The primary endpoint was antibody response to SARS-CoV-2 spike (S1) protein receptor binding domain (Elecsys Anti-SARS-CoV-2 immunoassay, Roche; cut-off ≥0.8 units/ml) 8 weeks after second vaccination. In addition, antibody response was measured with the Antibody CORonavirus Assay 2 (ABCORA 2). RESULTS: 430 patients were randomised and 412 were included in the intention-to-treat analysis (341 PLWH and 71 SOTR). The percentage of patients showing an immune response was 92.1% (95% confidence interval [CI] 88.4-95.8%; 186/202) for mRNA-1273 and 94.3% (95% CI 91.2-97.4; 198/210) for BNT162b2 (difference: 2.2%; 95% CI -7.1 to 2.7), fulfilling non-inferiority of mRNA-1273. With the ABCORA 2 test 89.1% had an immune response to mRNA-1273 (95% CI 84.8-93.4%; 180/202) and 89.5% to BNT162b2 (95% CI 85.4-93.7%; 188/210). Based on the Elecsys test, all PLWH had an antibody response (100.0%; 341/341), while for SOTR only 60.6% (95% CI 49.2-71.9%; 43/71) had titres above the cut-off. CONCLUSIONS: In immunocompromised patients the antibody response of mRNA-1273 was non-inferior to BNT162b2. PLWH had in general an antibody response, while a high proportion of SOTR had no antibody response.

3.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-312396

ABSTRACT

Background: In 2020, the COVID-19 pandemic led to an unprecedented volume of almost 3,000 clinical trials registered worldwide. We aimed to describe the COVID-19 clinical trial research agenda in Germany during the first year of the pandemic. Methods: We identified randomized clinical trials assessing interventions to treat or prevent COVID-19 that were registered in 2020 and recruited or planned to recruit participants in Germany. We requested recruitment information from trial investigators as of April 2021. Results: In 2020, 65 trials were completely (n=27) or partially (n=38) conducted in Germany. Most trials investigated interventions to treat COVID-19 (86.2%;56/65), in hospitalized patients (67.7%;44/65), with industry funding (53.8%;35/65). Few trials were completed (21.5%;14/65). Overall, 187,179 participants were planned to be recruited (20,696 in Germany), with a median number of 106 German participants per trial (IQR 40 to 345).  From the planned German participants, 13.4%  were recruited (median 15 per trial (IQR 0 to 44). Conclusions: The overall German contribution to the worldwide COVID-19 clinical trial research agenda was modest. Few trials delivered urgently needed evidence. Most trials did not meet recruitment goals. Evaluation and international comparison of the challenges for conducting clinical trials in Germany is needed.

4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-321965

ABSTRACT

• Background: Late 2019, a new highly contagious corona-virus SARS-CoV-2 has emerged in Wuhan, China, causing within two month a pandemic with the highest disease burden in elderly and people with pre-existing medical conditions. The pandemic has highlighted that new and more flexible clinical trial approaches, such as trial platforms, are needed to assess the efficacy and safety of interventions in a timely manner. The two existing Swiss cohorts of immunocompromised patients (i.e. Swiss HIV Cohort Study (SHCS) and Swiss Transplant Cohort Study (STCS)) are an ideal foundation to set-up a trial platform in Switzerland leveraging routinely collected data. Within a newly founded trial platform we plan to assess the efficacy of the first two mRNA SARS-CoV-2 vaccines that reached market authorisation in Switzerland in the frame of a pilot randomised controlled trial (RCT) while at the same time assessing the functionality of the trial platform.• Methods: We will conduct a multicenter randomised controlled, open-label, 2-arm sub-study pilot trial of a platform trial nested into two Swiss cohorts. Patients included in the SHCS or the STCS will be eligible for randomization to either receiving the mRNA vaccine Comirnaty® (Pfizer / BioNTech) or the Covid-19 mRNA Vaccine Moderna®. The primary clinical outcome will be change in pan-lg antibody response (pan-Ig anti-S1-RBD;baseline vs. three months after first vaccination). The pilot study will also enable us to assess endpoints related to trial conduct feasibility (i.e. duration of RCT set-up;time of patient recruitment;patient consent rate;proportion of missing data). Assuming vaccine reactivity of 90% in both vaccine groups we power our trial, using a non-inferiority margin such that a 95% two-sided confidence interval excludes a difference in favour of the reference group of more than 10%. A sample size of 380 (190 in each treatment arm) is required for a statistical power of 90% and a type I error of 0.025. The study is funded by the Swiss National Science Foundation (National Research Program NRP 78, ‘Covid-19’). • Discussion: This study will provide crucial information about the efficacy and safety of the mRNA SARS-CoV-2 vaccines in HIV patients and organ transplant recipients. Furthermore, this project has the potential to pave the way for further platform trials in Switzerland. Trial registration : NCT04805125

7.
Trials ; 22(1): 724, 2021 Oct 21.
Article in English | MEDLINE | ID: covidwho-1477452

ABSTRACT

BACKGROUND: Late 2019, a new highly contagious coronavirus SARS-CoV-2 has emerged in Wuhan, China, causing within 2 months a pandemic with the highest disease burden in elderly and people with pre-existing medical conditions. The pandemic has highlighted that new and more flexible clinical trial approaches, such as trial platforms, are needed to assess the efficacy and safety of interventions in a timely manner. The two existing Swiss cohorts of immunocompromised patients (i.e., Swiss HIV Cohort Study (SHCS) and Swiss Transplant Cohort Study (STCS)) are an ideal foundation to set-up a trial platform in Switzerland leveraging routinely collected data. Within a newly founded trial platform, we plan to assess the efficacy of the first two mRNA SARS-CoV-2 vaccines that reached market authorization in Switzerland in the frame of a pilot randomized controlled trial (RCT) while at the same time assessing the functionality of the trial platform. METHODS: We will conduct a multicenter randomized controlled, open-label, 2-arm sub-study pilot trial of a platform trial nested into two Swiss cohorts. Patients included in the SHCS or the STCS will be eligible for randomization to either receiving the mRNA vaccine Comirnaty® (Pfizer/BioNTech) or the COVID-19 mRNA Vaccine Moderna®. The primary clinical outcome will be change in pan-lg antibody response (pan-Ig anti-S1-RBD; baseline vs. 3 months after first vaccination; binary outcome, considering ≥ 0.8 units/ml as a positive antibody response). The pilot study will also enable us to assess endpoints related to trial conduct feasibility (i.e., duration of RCT set-up; time of patient recruitment; patient consent rate; proportion of missing data). Assuming vaccine reactivity of 90% in both vaccine groups, we power our trial, using a non-inferiority margin such that a 95% two-sided confidence interval excludes a difference in favor of the reference group of more than 10%. A sample size of 380 (190 in each treatment arm) is required for a statistical power of 90% and a type I error of 0.025. The study is funded by the Swiss National Science Foundation (National Research Program NRP 78, "COVID-19"). DISCUSSION: This study will provide crucial information about the efficacy and safety of the mRNA SARS-CoV-2 vaccines in HIV patients and organ transplant recipients. Furthermore, this project has the potential to pave the way for further platform trials in Switzerland. TRIAL REGISTRATION: ClinicalTrials.gov NCT04805125 . Registered on March 18, 2021.


Subject(s)
COVID-19 , Viral Vaccines , Aged , COVID-19 Vaccines , Humans , Immunocompromised Host , Multicenter Studies as Topic , Pilot Projects , RNA, Messenger , Randomized Controlled Trials as Topic , SARS-CoV-2
8.
J Clin Pharmacol ; 61(11): 1406-1414, 2021 11.
Article in English | MEDLINE | ID: covidwho-1241509

ABSTRACT

Glucocorticoids are frequently prescribed in inflammatory diseases and have recently experienced a boom in the treatment of COVID-19. Small studies have shown an effect of glucocorticoids on inflammatory marker levels, but definitive proof is lacking. We investigated the influence of prednisone on inflammatory biomarkers in a previous multicenter, randomized, placebo-controlled trial that compared a 7-day treatment course of 50-mg prednisone to placebo in patients hospitalized with community-acquired pneumonia. We compared levels of C-reactive protein (CRP), procalcitonin (PCT), leukocyte and neutrophil count between patients with and without glucocorticoid treatment at baseline and on days 3, 5, and 7 and at discharge by Wilcoxon tests and analysis of variance. A total of 356 patient data sets in the prednisone group and 355 in the placebo group were available for analysis. Compared to placebo, use of prednisone was associated with reductions in levels of CRP on days 3, 5, and 7 (mean difference of 46%, P < .001 for each time point). For PCT, no such difference was observed. Leukocyte and neutrophil count were higher in the prednisone group at all time points (mean difference of 27% for leukocytes and 33% for neutrophils, P <.001 for all time points). We conclude that after administration of glucocorticoids in community-acquired pneumonia, patients had lower CRP levels and increased leukocyte and neutrophil count as compared to the placebo group. PCT levels were not different between treatment groups. PCT levels thus may more appropriately mirror the resolution of infection compared to more traditional inflammatory markers.


Subject(s)
C-Reactive Protein/analysis , COVID-19 , Community-Acquired Infections , Leukocyte Count/methods , Pneumonia , Prednisone/administration & dosage , Procalcitonin/blood , Aged, 80 and over , Analysis of Variance , Biomarkers, Pharmacological/blood , COVID-19/drug therapy , COVID-19/epidemiology , Community-Acquired Infections/drug therapy , Community-Acquired Infections/epidemiology , Drug Monitoring/methods , Female , Glucocorticoids/administration & dosage , Humans , Male , Pneumonia/blood , Pneumonia/drug therapy , Pneumonia/epidemiology , Pneumonia/etiology , SARS-CoV-2 , Statistics, Nonparametric
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