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Infections with SARS-CoV-2 continue to cause significant morbidity and mortality. Interleukin (IL)-1 and IL-6 blockade have been proposed as therapeutic strategies in COVID-19, but study outcomes have been conflicting. We sought to study whether blockade of the IL-6 or IL-1 pathway shortened the time to clinical improvement in patients with COVID-19, hypoxic respiratory failure, and signs of systemic cytokine release syndrome.

Aim:Many questions of relevance to patients/society are not answered by industry-sponsored clinical trials. We consider whether there are benefits to governments in funding practice-oriented clinical trials. Methodology:A literature search including publications on institutions’ websites was performed and supplemented with information gathered from (inter)national stakeholders. Results:Areas were identified where public funding of clinical trials is of importance for society, such as head-to-head comparisons or medical areas where companies have no motivation to invest. The available literature suggests publicly funded research programs could provide a positive return on investment. The main hurdles (e.g., sufficient funding and absence of equipoise) and success factors (e.g., selection of research questions and research infrastructure) for the successful conduct of publicly funded trials were identified. Conclusion:Governments should see public funding of pragmatic practice-oriented clinical trials as a good opportunity to improve the selection and quality of treatments and stimulate efficient use of limited resources.

Background:Economic evaluations of companion diagnostics often fail to include the impact that tests have on the overall economic value of test–drug combinations. Methods:To illustrate the importance of test accuracy on the cost–effectiveness of companion diagnostics by means of examples. Data were extracted from the literature. Results:The accuracy of a test and in particularly its specificity, is often more influential on the overall cost–effectiveness results than the price of the test. Specificity becomes more crucial when prevalence of the biomarker is low. Multiple, simultaneous testing faces specific challenges regarding its overall specificity. Conclusion:This article opens a discussion on some fundamental points linked to economic evaluations of test–therapy combinations.

Over the past 50 years, medicines have made a huge contribution to improving the health status of populations. However, the level of pharmaceutical innovation varies widely, ranging from breakthrough treatments for life-threatening diseases to minor modifications of medicines that have been on the market for some time. Once innovative medicines approach the market, a system of measuring the level of innovation should be established. This perspective describes the current situation, the challenges and initiatives, and formulates recommendations for a coordinated EU action to measure the level of pharmaceutical innovation. In our opinion, comparative effectiveness research needs to play a central role in measuring the level of pharmaceutical innovation.

The goal of health care policies is to maximize the health of the population within the limits of the available budget and taking into account equity considerations. For innovative drugs, this means that an increasing number are being assessed in terms of their value for money, which is the amount of additional health that can be achieved per additional euro, pound, dollar, or other currency invested. Ideally such assessments and resulting appraisals and decisions should be made in a transparent and efficient way. Transparent means consisting of clear procedures and criteria such as relative effectiveness, cost effectiveness, budget impact, social, and ethical consequences. Transparent also means that stakeholders (physicians, patients, industry, and others) are involved in the assessment and decision‐making process. Efficient means that, on a European level, duplication of efforts is avoided by aligning the processes for market authorization and those for the assessment of value for money. Drug Dev Res 71: 457–462, 2010. © 2010 Wiley‐Liss, Inc.

The tolerability and immunogenicity of intradermal injections of a candidate HCV vaccine, based on the E1 protein of the hepatitis C virus (HCV), was examined in an exploratory study in healthy volunteers, in subjects with a history of resolved HCV infection, and in patients suffering from therapy-resistant chronic HCV. Sub-epidermal injection of three doses of 4 µg of non-adjuvanted E1 vaccine induced much weaker humoral and cellular immune responses in healthy subjects and chronic HCV patients than the intramuscular administration of 20 µg E1 formulated on alum. However, in three subjects who cleared HCV infection, intradermal administration of this low dose of E1 induced rapid and clear anamnestic responses. These data demonstrate that E1-specific immune responses can be induced in resolving HCV infections and that memory (B and T) cells can be restimulated with suboptimal doses of E1 antigen.

ABSTRACTSensitive and early detection of emerging hepatitis B virus (HBV) drug resistance may not only help monitor the viral dynamics associated with lamivudine treatment but could also improve therapeutic decision making. This is especially important when new antivirals effective against lamivudine-resistant HBV become available. A total of 159 serum samples from 33 chronic HBV patients receiving lamivudine treatment were analyzed at four centers for the presence of lamivudine-resistant mutations at codons 528 [180] (proposed revised nomenclature according to Stuyver et al. [Hepatology 33:751-757, 2001] shown in brackets), 552 [204], and 555 [207] of the HBV polymerase. Sequencing data were compared with results generated by the INNO-LiPA HBV DR line probe assay (LiPA), an assay based on reverse hybridization of amplified HBV DNA fragments with specific nucleotide probes immobilized on nitrocellulose strips. LiPA provided at least the same information as sequencing for 97.5% of all codons analyzed for codon 528 [180], 95% for codon 552 [204], and 100% for codon 555 [207]. The most common reason for discrepant or indeterminate results (0.4% and 1.5%, respectively) in a small percentage of the population tested could be attributed to polymorphisms not yet covered by LiPA probes. In at least five patients, a mutant could be detected earlier by LiPA than by sequencing. In 15 patients, LiPA detected mixed wild-type and mutant virus populations before viral breakthrough. These results demonstrate that INNO-LiPA HBV DR is a highly sensitive and easily applicable assay for the detection and monitoring of lamivudine-resistant mutations in chronic hepatitis B patients and that the assay is more sensitive than sequencing in detecting mixed mutant and wild-type sequences.

ABSTRACTWe evaluated the sensitivity and specificity of a new confirmatory test for treponemal antibodies, INNO-LIA Syphilis (Innogenetics NV, Ghent, Belgium), on a large number of sera from a clinical laboratory. This multiparameter line immunoassay (LIA) uses recombinant and synthetic polypeptide antigens derived from Treponema pallidumproteins. In a single-blinded cross-sectional retrospective study, 289 seronegative sera, 219 seropositive sera, and 23 sera with an indeterminate serological status for syphilis were analyzed. All sera were tested by the T. pallidumhemagglutination assay (TPHA), the immunoglobulin (IgG)-fluorescent T. pallidumabsorption assay (IgG-FTA-ABS), and the Venereal Disease Research Laboratory (VDRL) test. In addition, some seropositive samples were analyzed by the 19S-IgM-FTA-ABS test, an enzyme immunoassay (IgM-EIA), and the MarDx immunoblotting assay. Based on a consensus diagnosis derived from conventional serology, all of the sera were classified as positive, negative, or indeterminate, and the results were compared with the findings of the INNO-LIA Syphilis assay. The sensitivity and specificity of the LIA were 100% (219 of 219) and 99.3% (286 of 288), respectively. Compared to TPHA and IgG-FTA-ABS, the new test gave a significantly higher number (P= 0.021 and P< 0.0001, respectively) of correct results than either of the other two tests. The multiparameter INNO-LIA Syphilis assay is a useful confirmatory test for syphilis because it increases the reliability of syphilis diagnosis with respect to current conventional techniques.

ABSTRACTAlthough screening for Trypanosoma cruziantibodies is mandatory in most South American countries, current tests are insensitive and have poor specificity. A recently optimized line immunoassay (the INNO-LIA Chagas assay) for the serological confirmation of Chagas' disease was evaluated at a large blood bank in Sa~o Paulo, Brazil. Sera from blood donors who reacted in at least one of three serological screening assays (n= 1,604) and who returned for a follow-up were retested, and the donors were interviewed to assess their epidemiological risk. The results obtained by the confirmatory assay evaluated in this study were compared to those obtained by the three different screening assays. Upon consideration of the consensus results obtained by the three different screening assays as a “gold standard,” the INNO-LIA Chagas assay showed a sensitivity of 99.4% (95% confidence interval [CI], 98.3 to 99.9) and a specificity of 98.1% (95% CI, 96.6 to 99.0) for positive (n= 503) and negative (n= 577) sera. The INNO-LIA Chagas assay confirmed the results for significantly larger numbers of positive samples of at-risk individuals independent of the number of positive screening tests (P= 0.017, Mantel-Haenszel test). In conclusion, the INNO-LIA Chagas assay reliably confirmed the presence of antibodies toT. cruziand can be implemented as a confirmatory assay for Chagas' disease serology.

ABSTRACTThe commercially available diagnostic tests for syphilis are mostly based on the use of extracted antigens of Treponema pallidum. Pronounced cross-reactivities with other spirochete antigens are often reported. The aim of this study was to validate a novel multiparametric assay (the assay performed with the kit) INNO-LIA Syphilis for the confirmation of syphilis antibodies in a set of 840 documented human serum samples. All serum samples were previously tested at the French World Health Organization reference center for venereal diseases (Institute Alfred Fournier, Paris, France), with a consensus result provided for each sample. The study was conducted in two phases, with each phase involving a validation set (500 well-documented serum samples) and an exploratory set (340 serum samples) of serum samples, respectively. By measuring the sensitivity and specificity, we compared the result of the new assay with the consensus result on the basis of the results of a variable number of classical serological methods and clinical information when available. A sensitivity of 99.6% (95% confidence internal [CI], 98.5 to 99.9%) and a specificity of 99.5% (95% CI, 98.1 to 99.9%) were found for the new line immunoassay. Six of seven samples with indeterminate results by classical serology tested positive with the INNO-LIA Syphilis kit. This single multiparametric assay provides reliable confirmatory diagnostic information that must currently be obtained by the performance and interpretation of results of a combination of serological assays.

ABSTRACTWe carried out a multicenter performance evaluation of three new DNA-based human leukocyte antigen (HLA) typing assays: INNO-LiPA HLA-A Update, INNO-LiPA HLA-B Update, and INNO-LiPA HLA-DQB1 Update. After optimization, the accuracy rates were all 100%, and the final observed resolutions were 99.4, 92.4, and 85.6%, respectively. These rapid and easy-to-perform assays yielded results fully concordant with other DNA-based tissue typing tests.