In September 2022, we have identified the following access and policy-relevant scientific publications that caught our attention from the (digital) diagnostics perspective. Check them out:
Clinical value:
1. Circulating tumor DNA monitoring for early recurrence detection in epithelial ovarian cancer
The study examined the utility of circulating tumor DNA (ctDNA) as a prognostic biomarker for Epithelial ovarian cancer (EOC) by assessing its relationship with patient outcome and CA-125, pre-surgically and during post-treatment surveillance. The presence of ctDNA post-surgically is highly prognostic of reduced recurrence-free survival. CtDNA outperformed CA-125 in identifying patients at highest risk of recurrence. These results suggest that monitoring ctDNA could be beneficial in clinical decision-making for EOC patients.
2. Circulating tumor DNA predicts outcome in metastatic gastroesophageal cancer
This study analyzed the prognostic value of baseline and on-treatment ctDNA in metastatic gastroesophageal cancer (mGEC) using a region-specific next generation sequencing (NGS) panel. It concluded that the number of ctDNA mutations before start of first-line chemotherapy has prognostic value. Moreover, residual ctDNA after three cycles of systemic treatment is associated with inferior survival.
In this pragmatic, randomised controlled trial, they enrolled critically ill adults with pneumonia. Patients were assigned (1:1) to molecular testing of samples at the point-of-care or routine clinical care. The primary outcome was the proportion of patients who received results-directed antimicrobial therapy. The study conclude the use of molecular point-of-care testing in patients with pneumonia returned results more rapidly and identified more pathogens than conventional testing. This was associated with improvements in appropriate antimicrobial use and appeared safe.
4. Assessment of a Simplified Cell-Free DNA Method for Prenatal Down Syndrome Screening
At 16 sites, women at 10 to 20 weeks gestation provided informed consent, relevant information, and 2 to 3 blood samples. Rolling circle amplification (RCA) testing occurred post-enrollment, over 11 months. Detection rates were based on confirmed trisomic pregnancies; false-positive rates were based on unaffected pregnancies from the general population. The assessment of this simplified cfDNA-based system for prenatal screening for common trisomies performed in a prenatal screening laboratory is encouraging. Improved detection, low failure rates and rapid reporting can be achieved by collecting 2 samples. Future priorities should include achieving higher run precision using a single collection tube.
This study was performed at five hospitals in Japan between 2013 and 2016. Blood samples from 73 patients with clinically suspected sepsis yielded 18 positive blood cultures, and the isolated bacterial species were detectable using cdPCR-NALFIA in nine samples. Thirteen samples were positive on cdPCR-NALFIA. In total, 17 samples confirmed to have bacterial species were detectable using cdPCR-NALFIA and/or blood culture with a true positive rate of 76.5% and 64.7%, respectively. The combination of blood culture and cdPCR-NALFIA could improve the rate of detection of bacterial sepsis.
This study aimed to evaluate a Cardiometabolic Sutter Health Advanced Reengineered Encounter (CM-SHARE), a web-based application to visualize key EHR data, on the EHR use efficiency. By combining EHR audit log files and clinical information, the approach offers an innovative and scalable method and new measures that can be used to evaluate clinical EHR efficiency of digital tools used in clinical settings.
The objective of this study was to assess the impact of the use of a rapid molecular diagnostic test, the cobas® Influenza A/B & RSV Assay, during the clinical management of emergency department patients in four hospitals in the Brussels region. A comparison of the analytical performance of this test against antigen rapid tests and viral culture was performed as well as a time-to-result evaluation. The study concluded that the use of a rapid influenza and RSV molecular test improves the clinical management of patients admitted to the emergency department by providing a fast and reliable result. Their additional cost compared to antigen tests should be balanced with the benefit of their analytical performance, leading to efficient reductions in the need for isolation and antibiotic use.
8. Multicenter performance evaluation of the Elecsys HCV Duo immunoassay
The diagnostic accuracy of the Elecsys® HCV Duo antigen-antibody combination immunoassay (Roche Diagnostics GmbH) was evaluated for the detection of hepatitis C virus (HCV) infection, versus commercially available comparators. The study concluded that the Elecsys HCV Duo immunoassay shows high diagnostic accuracy, reduces the diagnostic window, and could be used when NAT is not possible.
9. Xpert MTB/RIF Ultra assay for tuberculosis disease and rifampicin resistance in children
The current review updates evidence on the diagnostic accuracy of Xpert Ultra in children presumed to have tuberculosis disease (pulmonary tuberculosis, tuberculous meningitis, lymph node tuberculosis, and rifampicin resistance). The authors found Xpert Ultra sensitivity to vary by specimen type, with sputum having the highest sensitivity, followed by gastric aspirate and stool. Nasopharyngeal aspirate had the lowest sensitivity. Xpert Ultra specificity was high against both microbiological and composite reference standards. However, the evidence base is still limited, and findings may be imprecise and vary by study setting. Although they found Xpert Ultra accurate for detection of rifampicin resistance, results were based on a very small number of studies that included only three children with rifampicin resistance.
Cost effectiveness, HTA, pricing:
The aim of the study is to assess the cost-effectiveness of using next-generation sequencing (NGS) compared to sequential single-testing (SST) for molecular diagnostic and treatment of patients with advanced non-small cell lung cancer (NSCLC) from a Spanish single-center perspective, the Hospital Universitario Virgen del Rocio (HUVR). The implementation of NGS at HUVR for the diagnostic of patients with advanced NSCLC provides significant clinical benefits compared to SST in terms of alterations detected, treatment with targeted-therapies and clinical-trial enrollment, and could be considered a cost-effective strategy even though costs increase.
The study aims to estimate the expected change to the mean number of diagnostic tests used, and the associated costs from a decision to use WES early in the diagnostic pathways of pediatric phenotypes, as compared to Existing Practice. Retrospective data from a patient cohort recruited under the Singapore Undiagnosed Disease Program from a tertiary hospital in Singapore, for the period October 2004 to September 2020, was analyzed. The study concluded that uncertainty assessment for multiple congenital anomalies (MCA) and global developmental delay (GDD) patients showed a respective likelihood of 86.9% and 97.4% for cost savings. Adoption of alternate diagnostic pathways with early WES in selected pediatric subgroups are likely to reduce costs, when compared to Existing Practice. Benefits arising from earlier diagnosis, and the potential cost savings could mitigate the large initial cost of implementing WES in Asian settings.
12. Search for a time- and cost-saving genetic testing strategy for maturity-onset diabetes of the young
Aim of the present study was a search for optimal time- and cost-saving strategies by comparing two approaches of genetic testing of participants with clinical suspicion of maturity-onset diabetes of the young (MODY). A total of 121 consecutive probands referred for suspicion of MODY (Group A) were screened using targeted NGS (tNGS), while the other 112 consecutive probands (Group B) underwent a single gene test based on phenotype, and in cases of negative findings, tNGS was conducted. The two-step approach represented a better strategy for genetic investigation of MODY concerning time and costs compared to direct tNGS. Although a single-gene investigation clarified the diabetes aetiology in the majority of cases, tNGS could reveal rare causes of MODY and expose possible limitations of both standard genetic techniques and clinical evaluation.
Healthcare systems, utilization, initiatives, guidelines:
Since 2020 Digital Health Applications (DiHA) in Germany have been undergoing a systematic pathway to be reimbursed by statutory health insurance (SHI) which is attracting attention in other European countries. The study investigates coverage decisions on DiHA and the underlying evidence on health care effects, which legally include both medical outcomes and patient-centred structural and procedural outcomes. By February 2022, 30 DiHA had been included in the DiHA registry, one third of them permanently and two thirds conditionally. Most DiHA were therapeutic applications for mental illness based on cognitive behavioural therapy. For all permanently included DiHA, randomised controlled trials were conducted to demonstrate the impact on health care effects. While medical outcomes were investigated for all of these DiHA, patient-centred structural and procedural outcomes were rarely investigated. The majority of clinical trials showed a high risk of bias, mainly due to insufficient reporting quality. Overall, the prices for DiHA covered by SHI are on average around € 150 per month (min. € 40; max. € 248). The study conclude that Evidence-based decision-making on coverage of DiHA leaves room for improvements both in terms of reporting-quality and the use of patient-centred structural and procedural outcomes in addition to medical outcomes. With appropriate evidence, DiHA can offer an opportunity as an adjunct to existing therapy while currently the high risk of bias of the trials raises doubts about the justification of its high costs.
Gastric cancer is an inflammation-related cancer triggered by Helicobacter pylori infection. Understanding of the natural disease course has prompted the hypothesis that gastric cancer can be prevented by administering a short-course antibiotic treatment to eradicate the H. pylori infection and interrupt this carcinogenic cascade. Results from randomized controlled trials and cohort studies have repeatedly confirmed this concept, which has moved attention from individual management of H. pylori infection to population-wide implementation of screening programs. These programs, with increased accessibility and geographic coverage in progress, will accelerate the decline in morbidity, mortality, and associated costs of this preventable malignancy.
This article reviews the recently established fast-track integration of DiGA in the German reimbursement market, with emphasis on the current impact for manufacturers, healthcare providers, and people with diabetes. The German DiGA fast track is contextualised with corresponding initiatives in Europe. The study concluded that the DiGA fast track needs to be further enhanced to cope with remaining skepticism and contribute even more to a value-based diabetes care.
The objective of the paper is to establish a data-based method to estimate the economic impact to a health system of interventions promoting primary care visits for people with diabetes who have been historically unengaged with their care. The proposed economic model can help health systems understand and evaluate the estimated economic benefits of interventions focused on primary care and prevention for patients with diabetes as well as help intervention developers determine pricing for their product.