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„Innovationen unter Druck: Haben Spitzenforschung & Spitzenmedizin eine Zukunft?“ Unter diesen Titel stellte das forschende Pharmaunternehmen Roche sein diesjähriges Pressedinner anlässlich des Hauptstadtkongresses 2024 – erneut im österreichischen Restaurant Ottersbach zu Berlin mit den wohl besten Kalbsschnitzeln westlich Wiens. Diesmal referierten Prof. Wolfgang Schütte, Ärztlicher Direktor, Klinik für Innere Medizin II – Pneumologie am Krankenhaus Martha-Maria Halle-Dölau, der sich das Thema „Klinische Forschung: Verliert Deutschland den Anschluss?“ vornahm, und Friedrich Fichtner, Access Lead Strategic Pricing & Reimbursement der Roche Pharma AG, der in seinem Vortrag ausführte, warum ein AMNOG 2.0 benötigt wird. Fichtners Vortrag steht im Fokus dieser Berichterstattung.

Background: In the last decade, point of care testing (POCT) such as lateral flow immunoassays (LFIA) were developed for rapid TSH measurement. Most of these TSH-LFIAs are designed for qualitative measurements (i.e., if TSH values > 5, or >15 IU/L) and as screening tests for primary hypothyroidism in children and adults. Serum or plasma, but not venepuncture whole-blood or fingerstick/capillary, are usually used to quantify TSH accurately. Studies on performance evaluation of TSH-LFIAs POCT using venepuncture or fingerstick whole-blood are limited. Additionally, limited studies evaluated the performance and validity of TSH-LFIAs POCT compared to valid and reliable reference methods. To our knowledge, this is the first study to evaluate three different blood withdrawal techniques for evaluating POCT of TSH. Aim: We aim to evaluate the performance of a new fluorescence-based LFIA and its Finecare™ fluorescent reader for quantitative measurement of TSH from a fingerstick, venepuncture whole-blood, and serum. Methods: 102 fingerstick, venepuncture whole-blood, and serum samples (with normal and abnormal TSH values) were analyzed by Finecare™ Rapid Quantitative LFIA test and Roche cobas® e 601 as a reference test. Results: Using serum, when compared to cobas® e 601 reference method, Finecare™ showed high sensitivity [90.5 % (69.6–98.8)] and specificity [96.3 % (89.6–99.2)] for diagnosis of thyroid abnormalities (4.5 mIU/L). The actual test values (mIU/L) of Finecare™ showed excellent agreement (Cohen's Kappa = 0.85) and strong correlation (r = 0.93, p

Background. The anti-Müllerian hormone (AMH) is gaining attention as a key factor in determining ovarian reserve and polycystic ovarian syndrome, and its clinical applications are becoming more widespread worldwide. Objective. To identify the most accurate formula for converting AMH assay results between different platforms, so that the developed AMH converter can be used to reduce the need for multiple AMH tests at different hospitals. Methods. Assuming that the Beckman Access, Kangrun, and Roche Elecsys® AMH assays fit a linear relationship from the lowest to the highest concentration (a global relationship), we used Passing-Bablok regression to determine the conversion equation between each two assays. When the relationship between two AMH assays was a local one, spline regression was used. Bland-Altman plots were drawn to check systemic bias and heterogeneity of variance across different ranges of values. The fitting effects of the models were evaluated using the squared coefficient of determination (r2), adjusted r2, root mean square error (RMSE), Akaike information criterion (AIC), and corrected AIC. Results. The coefficient of variance for multiple controls in the Kangrun, Roche, and Beckman assays was lower than 5%, and the bias of multiple controls was lower than 7%. A global linear relationship was observed between the Kangrun and Roche assays, with the intercept being zero, for which Passing-Bablok regression was employed for data conversion between the two platforms. For the other two pairs of platforms, i.e., Roche and Kangrun or Beckman and Kangrun, spline regression was applied, with the intercepts not including zero. The six corresponding formulas were developed into an online AMH converter (http://121.43.113.123:8006). Conclusion. This is the first time Passing-Bablok plus spline regression has been used to convert AMH concentrations from one assay to another. The formulas have been developed into an online tool, which makes them convenient to use in practical applications. [ABSTRACT FROM AUTHOR]

Objective: To verify the analytical performance of cobas® HBV PCR and cobas® HCV PCR assays with Abbott m2000 RealTime System as the reference method. Design: De-identified residual, archived patient specimens, and College of American Pathologists (CAP) proficiency testing samples were used. Analytical parameters verified were accuracy, precision, limit of detection (LOD), linear range, and cross-contamination. Experiments were designed in accordance with Clinical Laboratories Standards Institute (CLSI) guidelines and CAP standards. Analysis of accuracy was done through regression plots and Bland Altman analyses. Precision was analyzed through coefficient of variation and ANOVA; LOD through probit analysis; and linear range through polynomial fit analysis. Results: The regression plots for accuracy showed a slope nearing 1, with a y-intercept close to zero, while Bland Altman analyses also showed no systematic evidence of bias, though concordance of results was not perfect near the lower limit of quantification. Coefficients of variation were all below 15%, while ANOVA returned p-values above 0.99, indicating no statistically significant imprecision. The LOD verified were an order of magnitude higher than the manufacturer reported ones for both assays, while the linear range verified was more limited. Within the verified range, polynomial fit analysis showed line to be the best fit for the data. Conclusions: cobas® HBV PCR and cobas® HCV PCR assays showed acceptable accuracy, acceptable precision, as well as no evidence of cross-contamination. The LOD verified were higher, and linear ranges more limited than those reported by the manufacturer. Verifications of these may be limited by availability of appropriate testing specimens.

With widespread global COVID-19 vaccine coverage, a scalable, cost-effective, and standardized tool to ascertain post-vaccine immunity is a dire need. Neither clinical evaluations of vaccine efficacy, nor live virus antibody neutralization assays fulfill these criteria. Commercially available anti-S binding immunological assays have the potential to fill this gap, but need to be systematically evaluated for their utility to serve as surrogates for the aforementioned, widely accepted tools of determining vaccine efficacy. In this study, we evaluated an anti-S binding immunological assay (Roche Elecsys Anti-SARS-CoV-2 S) by utilizing two hundred and fifty-five archived serum specimens, either pre-pandemic, or those exposed to natural infections or vaccines with their neutralizing titers pre-determined through a live virus, pseudotyped antibody neutralization assay. Roche Elecsys Anti-SARS-CoV-2 S demonstrated good sensitivity (98%) and specificity (99%), just as has been reported in some other previously conducted studies using this assay. Only a mild correlation, however, with the live virus pseudotyped lentivirus antibody neutralization assay (Spearman's r = 0.26) was observed. We conclude that, as such, Elecsys Anti-SARS-CoV-2 S has a high sensitivity and specificity for detecting anti-SARS-CoV-2 S proteins, though the assay does not always correlate well with live virus assays for quantitative outcomes.

Macroprolactin cross-reacts in immunoassays for prolactin causing apparent hyperprolactinaemia (macroprolactinaemia) and consequent misdiagnosis and mismanagement of patients. We determined the prevalence of macroprolactinaemia using prolactin immunoassays with reported "high" (Tosoh) or "low" cross-reactivity (Roche) with macroprolactin. We additionally modelled the effects of increasing the screening threshold on workload and sensitivity in the detection of macroprolactinaemia. A review of routine requests for prolactin received in a 12 month period identified 670 sera with hyperprolactinaemia (Tosoh assay). Treatment with polyethylene glycol (PEG) precipitation demonstrated normal levels of monomeric prolactin in 165 sera (24.6%) indicating macroprolactinaemia. In the macroprolactinaemic cohort, total prolactin levels were lower with the Roche assay (473 ± 132 mU/L; mean ± SD) compared to the Tosoh assay (683 ± 217 mU/L), p < 0.005. The prevalence of macroprolactinaemia was also lower with the Roche assay (6.2%). The number of samples that required screening for macroprolactinaemia fell by 14% when Roche gender specific total prolactin reference limits were applied. Use of a higher screening threshold (700 mU/L) reduced the screening workload considerably (Roche by 45%, Tosoh by 37%) however, the sensitivity of detection of macroprolactinaemia decreased markedly (Roche 90%, Tosoh 59%). Macroprolactin interferes in both Tosoh and Roche prolactin immunoassays. Use of an assay with a relatively low cross reactivity with macroprolactin, e.g. Roche, will lead to a modest reduction in the screening workload. Increasing the screening threshold above the upper limit of the assay reference interval will also reduce the screening workload but leads to disproportionate increases in the number of cases of macroprolactinaemia which are missed. [ABSTRACT FROM AUTHOR]

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread worldwide. Here, we evaluated the performance of two quantitative antigen (Ag) tests, the Roche and Lumipulse Ag tests, using automated platforms. Methods: We collected 637 nasopharyngeal swab samples from 274 individuals. Samples were subjected to quantitative reverse transcription PCR (RT-qPCR), the Roche Ag test and Lumipulse Ag test. Results: When RT-qPCR was used as a reference, the overall concordance rate of the Roche Ag test was 77.1% (491/637) with 70.0% (341/487) sensitivity and 100% specificity (150/150). When inconclusive results of the Lumipulse Ag test were excluded, the overall concordance rate of the Lumipulse Ag test was 88.3% (467/529) with 84.8% (330/389) sensitivity and 97.9% (137/140) specificity. The overall concordance rate between the Roche and Lumipulse Ag tests was 97.9% (518/529) with 96.7% (322/333) sensitivity and 100% (196/196) specificity. Quantitative Ag levels determined using the Roche and Lumipulse Ag tests were highly correlated (R2 = 0.922). The Roche and Lumipulse Ag tests showed high concordance up to nine days after symptom onset, with progressively lower concordance after that. Conclusions: The Roche and Lumipulse Ag tests showed equivalent assay performance and represent promising approaches for diagnosing coronavirus disease 2019.

Background: The detection of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is mandatory for the diagnosis, retrospective assessment of disease progression, and correct evaluation of the current infection situation in the population. Many such assays have been launched by various manufacturers. Unfortunately, the new US Food and Drug Administration emergency use regulations have resulted in a situation where laboratories have to perform their own validation studies but many of these laboratories do not have the biobank needed to conduct the studies. Methods: We introduce a method that allows institutions to quickly perform a verification study in a low-prevalence infection situation. As proof of concept, we used the Roche Elecsys® anti-SARS-CoV-2 electrochemiluminescence immunoassay and an SAP-based hospital information system. The Shenzhen YHLO Biotech IgM and IgG assay targeting other surface patterns was used as a confirmatory test. Results: The Roche assay demonstrated a limit of detection of 0.069 cutoff index and successfully passed the performance validation according to Clinical and Laboratory Standards Institute EP15-A3. The study population of 627 inpatients has a median age of 64 years, and approximately 13% of the group were under intensive care at the respective time point. All patients included tested negative for SARS-CoV-2 infection by quantitative reverse transcription polymerase chain reaction (cobas® 6800, Roche, Mannheim, Germany). Only one false-positive result was obtained, resulting in a specificity for the Roche Elecsys anti-SARS-CoV-2 test of 99.84% and a negative predictive value of 99.98%. Conclusions: The anonymized use of residual material enables quick evaluation of anti-SARS-CoV-2 immunoassays, as shown in this work with the Roche Elecsys assay. Comparison of the control population with economic data makes it possible to validate the sampling set and therefore to determine diagnostic specificity. By use of the approach chosen, it was shown that the Roche test achieved very good results in terms of diagnostic specificity, reproducibility, and limit of detection.

Background: Cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) are the most commonly used tumor biomarkers for ovarian cancer (OC) screening and diagnosis. The risk of ovarian malignancy algorithm (ROMA) score uses these markers, as detected by the Roche system, to predict the risk of OC. This study sought to assess the performance of the Mindray system in detecting CA125 and HE4 for ROMA score calculation in clinical settings., Methods: Consecutive OC patients and patients with benign pelvic masses were screened and enrolled in this study. The CA125 and HE4 levels of these patients were measured using both the Mindray and Roche systems. The ROMA score for each patient was calculated. Diagnostic performance was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve., Results: The HE4 and CA125 levels were significantly higher in the patients with OC than the patients with benign ovarian masses. Both detection systems showed high efficiency in detecting ovarian cancer. For the premenopausal OC patients, the AUC values for the ROMA score, HE4, and CA125 were 0.866, 0.852, and 0.879, respectively, using the Roche system, and 0.911, 0.902, and 0.883, respectively, using the Mindray system. For the postmenopausal OC patients, the AUC values for the ROMA score, HE4, and CA125 were 0.962, 0.920, and 0.953, respectively, using Roche system, and 0.966, 0.924, and 0.959, respectively, using the Mindray system. The correlation analysis showed strong agreement between the two systems. Among the patients who experienced recurrence, we observed a significant increase in both HE4 and CA125 levels compared to baseline using the Mindray system., Conclusions: The Mindray and Roche systems provide consistent results. The Mindray system can be used to detect HE4 and CA125 for ROMA score calculation., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-24-1107/coif). C.L. serves as an unpaid editorial board member of Translational Cancer Research from August 2024 to July 2026. C.L. has received grant funding for research from RefleXion Medical and AstraZeneca. The other authors have no conflicts of interest to declare., (2024 Translational Cancer Research. All rights reserved.)

Background: A large discordance in the diagnosis and potential management of hypothyroidism using Abbott and Roche thyroid assays has been reported recently. The difference in Abbott and Roche thyroid-stimulating hormone (TSH) results in these studies was larger than anticipated from the external quality assessment (EQA) reports. Methods: Abbott and Roche TSH method means in UK NEQAS for thyroid hormones distributions 430 to 454 were compared against the amount of TSH spiked. A TSH deplete serum pool was spiked with various concentrations of pooled high TSH serum and 3rd WHO International Standard for TSH (WHO-IS). Four serum pools with TSH close to clinical decision limits were spiked with two concentrations of WHO-IS. Results: On review of EQA data, median (IQR) Roche: Abbott TSH ratio was lower (p < 0.001) in 48 pools spiked with TSH (1.11 (1.07–1.16)) compared to 41 pools not spiked (1.29 (1.25–1.31)) and the decrease was proportionate to the contribution of spiked TSH to total TSH in the samples (ρ=−0.908, p < 0.001). In spiking experiments, the relationship of Roche and Abbott TSH was different in TSH deplete pool spiked with WHO-IS (RocheTSH=1.13*AbbottTSH–0.52) and high TSH serum (RocheTSH=1.43*AbbottTSH–0.50), respectively. The Roche: Abbott TSH ratio decreased and the method agreement improved on spiking serum pools with WHO-IS. Conclusion: Abbott and Roche TSH assays are not in harmony in human serum samples but the agreement was better in samples spiked with WHO-IS which contains pituitary-derived TSH. Use of pituitary-derived TSH spiked samples, such as provided by EQA schemes, may mask clinically significant between-assay differences. [ABSTRACT FROM AUTHOR]

Background: The ability to rapidly detect severe accurate respiratory syndrome coronavirus virus-2 (SARS-CoV-2) and influenza virus infection is vital for patient care due to overlap in clinical symptoms. Roche's cobas® Liat® SARS-CoV-2 & Influenza A/B Nucleic Acid Test used on the cobas Liat was granted approval under the Food and Drug's Emergency Use Authorization for nasopharyngeal (NP) and nasal swabs collected in viral/universal transport medium (VTM/UTM). However, there is a critical need for media that inactivates the virus, especially when specimens are collected in decentralized settings. This study aimed to investigate the use of PrimeStore Molecular Transport Medium® (PS-MTM®), designed to inactivate/kill and stabilize RNA/DNA for ambient transport and preprocessing of collected samples. Methods: A limit of detection (LOD) using serially diluted SARS-CoV-2 RNA in PS-MTM and routine UTM was established using standard quantitative PCR (qPCR). Additionally, a clinical panel of NP and oral swabs collected in PS-MTM during the 2020 coronavirus disease 2019 pandemic were evaluated on the cobas Liat and compared to "gold standard" qPCR on an ABI-7500 instrument. Results: SARS-CoV-2 RNA LOD using standard qPCR was equivalent on the cobas Liat instrument. cobas Liat detection from oral/NP swabs in PS-MTM media exhibited equivalent positive percent agreement (100%) and negative percent agreement (96.4%). Conclusion: PS-MTM and the Roche cobas Liat are compatible and complimentary devices for respiratory specimen collection and rapid disease detection, respectively. PS-MTM is equivalent to standard VTM/UTM with the added benefit of safe, noninfectious sample processing for near-patient testing. [ABSTRACT FROM AUTHOR]

• We compared the results of quantitative SARS-CoV-2 Ag tests of Roche and Lumipulse. • Both Ag tests were positive for samples containing high viral loads. • Quantitative Ag levels correlated with viral loads and threshold cycle values. • Quantitative Ag levels determined using the two Ag tests were highly correlated. • The two Ag tests showed high concordance up to 9 days after symptom onset. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread worldwide. Here, we evaluated the performance of two quantitative antigen (Ag) tests, the Roche and Lumipulse Ag tests, using automated platforms. We collected 637 nasopharyngeal swab samples from 274 individuals. Samples were subjected to quantitative reverse transcription PCR (RT-qPCR), the Roche Ag test and Lumipulse Ag test. When RT-qPCR was used as a reference, the overall concordance rate of the Roche Ag test was 77.1% (491/637) with 70.0% (341/487) sensitivity and 100% specificity (150/150). When inconclusive results of the Lumipulse Ag test were excluded, the overall concordance rate of the Lumipulse Ag test was 88.3% (467/529) with 84.8% (330/389) sensitivity and 97.9% (137/140) specificity. The overall concordance rate between the Roche and Lumipulse Ag tests was 97.9% (518/529) with 96.7% (322/333) sensitivity and 100% (196/196) specificity. Quantitative Ag levels determined using the Roche and Lumipulse Ag tests were highly correlated (R2 = 0.922). The Roche and Lumipulse Ag tests showed high concordance up to nine days after symptom onset, with progressively lower concordance after that. The Roche and Lumipulse Ag tests showed equivalent assay performance and represent promising approaches for diagnosing coronavirus disease 2019. [ABSTRACT FROM AUTHOR]

Objectives: Thyroid dysfunction in pregnancy is associated with increased risk of adverse outcomes to mother and child. Trimester-specific reference intervals for thyroid function tests are not routinely provided by clinical laboratories. In this study, we present first- and second-trimester-specific reference intervals in a US population for thyroid-stimulating hormone (TSH), free thyroxine (FT4), total thyroxine (T4), and total triiodothyronine (T3) measured on Roche analyzers.Methods: We used patient samples from first- and second-trimester prenatal screening. Samples were limited to singleton pregnancies and negative screening results for thyroid peroxidase and thyroglobulin antibodies. Analytes (TSH, FT4, T4, and T3) were measured on a Roche Modular e170 then verified on a Roche cobas e801.Results: The reference intervals established on the e170 and verified on the e801 for the first trimester were 0.16 to 2.82 mIU/L for TSH, 12.0 to 18.5 pmol/L for FT4, 62.8 to 177.9 nmol/L for T4, and 1.5 to 3.4 nmol/L for T3. The reference intervals for the second trimester were 0.40 to 3.62 mIU/L for TSH, 10.2 to 16.6 pmol/L for FT4, 66.6 to 176.0 nmol/L for T4, and 1.56 to 3.6 nmol/L for T3.Conclusions: This is the first report of trimester-specific reference intervals for thyroid function tests on Roche analyzers in the United States, and it is consistent with worldwide reports. [ABSTRACT FROM AUTHOR]

Objective: We assessed the commutativity of Roche and Abbott thyroid assays in the diagnosis and management of subclinical hypothyroidism (SCH). The Roche and Abbott thyroid assays are used by approximately 75% of clinical laboratories in the UK. Method: Consecutive samples received from primary care on patients with SCH who had a raised thyroid‐stimulating hormone (TSH) <10 mIU/L and a normal free thyroxine (fT4) from two laboratories using either Roche or Abbott thyroid assays were identified over 10 working days. Following identification, samples were analysed at the other site within 24 hours. Diagnostic and management discordance were studied using the relevant manufacturer‐provided reference ranges. Results: We identified 93 patients with SCH (53 using the Roche assay). Roche TSH and fT4 results were respectively 40% ± 15% and 16% ± 7% higher (P <.001) compared to Abbott results. Of the 93 patients, 41 (44%) were concordant for SCH on both methods. Of the 53 patients with SCH on the Roche assays, 40 (75.5%) had normal thyroid function and 13 (24.5%) had SCH when analysed using the Abbott assays. Of the 40 patients with SCH on the Abbott assays, 28 (70%) had SCH and 12 (30%) had results indicative for levothyroxine replacement when analysed on the Roche assays. Of these 12 patients, four had TSH > 10 mIU/L, five had low fT4 and three had both. Conclusion: The diagnosis and management of SCH is strikingly different when using TSH and fT4 assays provided by Abbott Laboratories and Roche Diagnostics. Clinicians and laboratorians should be aware that between‐assay differences and variations in reference ranges will directly impact the diagnosis and management of subclinical hypothyroidism. [ABSTRACT FROM AUTHOR]