Immunohistochemistry should undergo robust validation equivalent to that of molecular diagnostics

2015 ◽  
Vol 68 (10) ◽  
pp. 766-770 ◽  
Author(s):  
Kelly Elliott ◽  
Stephen McQuaid ◽  
Manuel Salto-Tellez ◽  
Perry Maxwell
Keyword(s):  
Molecular Diagnostics ◽  
Clinical Care ◽  
Treatment Options ◽  
Subjective Assessment ◽  
Molecular Diagnostic ◽  
Evidence Based ◽  
Uncertainty Of Measurement ◽  
Prognostic Information ◽  
Iso 15189 ◽  
Diagnostic Histopathology

Immunohistochemistry (IHC) is a widely available and highly utilised tool in diagnostic histopathology and is used to guide treatment options as well as provide prognostic information. IHC is subjected to qualitative and subjective assessment, which has been criticised for a lack of stringency, while PCR-based molecular diagnostic validations by comparison are regarded as very rigorous. It is essential that IHC tests are validated through evidence-based procedures. With the move to ISO15189 (2012), not just of the accuracy, specificity and reproducibility of each test need to be determined and managed, but also the degree of uncertainty and the delivery of such tests. The recent update to ISO 15189 (2012) states that it is appropriate to consider the potential uncertainty of measurement of the value obtained in the laboratory and how that may impact on prognostic or predictive thresholds. In order to highlight the problems surrounding IHC validity, we reviewed the measurement of Ki67and p53 in the literature. Both of these biomarkers have been incorporated into clinical care by pathology laboratories worldwide. The variation seen appears excessive even when measuring centrally stained slides from the same cases. We therefore propose in this paper to establish the basis on which IHC laboratories can bring the same level of robust validation seen in the molecular pathology laboratories and the principles applied to all routine IHC tests.

scholarly journals Toward harmonization of clinical molecular diagnostic reports: findings of an international survey

2018 ◽  
Vol 0 (0) ◽  
Author(s):  
Deborah A. Payne ◽  
Katarina Baluchova ◽  
Graciela Russomando ◽  
Parviz Ahmad-Nejad ◽  
Cyril Mamotte ◽  
...  
Keyword(s):  
Molecular Diagnostics ◽  
Clinical Decision Making ◽  
Clinical Chemistry ◽  
Clinical Decision ◽  
Molecular Diagnostic ◽  
Molecular Testing ◽  
End User ◽  
Iso 15189 ◽  
Reporting Practices ◽  
Reporting Phase

Abstract Background: The International Organization for Standardization (ISO) 15189 standard provides recommendations for the postexamination reporting phase to enhance quality in clinical laboratories. The purpose of this study was to encourage a broad discussion on current reporting practices for molecular diagnostic tests by conducting a global survey of such practices. Methods: The International Federation of Clinical Chemistry and Laboratory Medicine’s Committee for Molecular Diagnostics (IFCC C-MD) surveyed laboratories on selected ISO 15189 recommendations and topics. The survey addressed the following aspects: (1) laboratory demographics, (2) report format, (3) result reporting/layout, (4) comments in report and (5) interpretation and clinical decision-making information. Additionally, participants indicated categories needing standardization. Results: Sixteen responses from laboratories located in Asia, Europe, the Middle East, North America and South America were received. Several categories yielded 100% agreement between laboratories, whereas other categories had less than or equal to 50% concordance. Participants scored “nomenclature” and “description of methodologies” as the two most frequently cited aspects needing standardization. Conclusions: The postexamination phase requires extensive and consistent communication between the laboratory, the healthcare provider and the end user. Surveyed laboratories were most likely to follow explicit ISO 15189 recommendations vs. recommendations when the term(s) “where appropriate or where applicable” was used. Interpretation and reporting of critical values varied among participants. Although the outcome of this study may not fully represent the practices of all molecular testing laboratories in countries around the world, the survey identified and specified several recommendations that are requirements for harmonized reporting in molecular diagnostics.

scholarly journals 2181. Yield and Impact of Molecular Diagnostics for Pathogen Detection in Pediatric Patients: 16/18S rRNA PCR and Noninvasive Assays

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S740-S741
Author(s):  
Angela Chun ◽  
Taylor Heald-Sargent ◽  
Michael Malczynski ◽  
William J Muller ◽  
Chao Qi ◽  
...  
Keyword(s):  
Molecular Diagnostics ◽  
18S Rrna ◽  
Pediatric Patients ◽  
Clinical Care ◽  
High Yield ◽  
Molecular Diagnostic ◽  
Clinical Samples ◽  
Molecular Testing ◽  
Rrna Gene ◽  
Fungal Culture

Abstract Background Molecular diagnostic tests can identify bacterial and fungal pathogens from clinical samples. Nucleic acid detection tests include 16S and 18S rRNA gene PCR (16/18S PCR) and plasma next-generation sequencing (NGS). Other assays (fungal galactomannan and 1,3-β-d-glucan) detect structural factors. Our objective was to assess the utilization, yield, and impact of molecular diagnostics in pediatric patients who had samples sent for 16/18S PCR. Methods Sterile site fluid or tissue specimens were collected as part of standard care at Lurie Children’s Hospital, cultured, and sent to Northwestern Memorial Hospital for 16/18S PCR as clinically indicated. Medical records were reviewed for diagnostics, antibiotics, and clinical course. Results From 1/2016–8/2018, 236 samples were sent for 16 and/or 18S PCR from 183 patients. 83% had a concurrent ID consult. 16S PCR was done on 215 samples, 42 (20%) were positive, and 36 yielded species identification (Table 1). Antibacterial agents were administered prior to specimen collection in 73% and did not affect likelihood of positive 16S PCR. 18S PCR was sent on 163 samples; 12 (7.4%) were positive (Table 2) of which 10 were from immunocompromised hosts. 40% of patients were on antifungals prior to sample acquisition. 16/18S PCR impacted antimicrobial decision-making in 70 cases (30%). A pathogenic fungus was detected by PCR but not culture in 2 cases. Time to positivity of fungal culture was 1–15 days. Fungal culture was positive in 5 cases with-negative 18S PCR. Seventeen patients had positive serum 1,3-ß-D-glucan and/or galactomannan: 3 of which had positive 18S PCR, 5 with fungal growth, 5 presumed infection based on imaging, 1 Nocardia, and 3 noninfectious etiology. Plasma NGS was sent on 45 cases, was positive in 34, and affected clinical management in 10. Conclusion 16S PCR can identify bacterial pathogens in the setting of negative culture and impact clinical care. Abscess, bronchial/pleural fluid, and brain/organ tissue were high yield specimens. 18S PCR can provide expeditious fungal identification in cases of suspected invasive disease, but fungal culture and serum molecular testing increase diagnostic yield. No single fungal test is comprehensive. Plasma NGS had relatively high yield and clinical impact in selected patients. Disclosures All authors: No reported disclosures.

scholarly journals Molecular diagnostics in oncology: new trends

2020 ◽  
Vol 19 (4) ◽  
pp. 25-32
Author(s):  
Evgeny N. Imyanitov
Keyword(s):  
Molecular Diagnostics ◽  
New Technologies ◽  
Ex Vivo ◽  
Treatment Options ◽  
Diagnostic Procedures ◽  
Molecular Diagnostic ◽  
Invasive Approach ◽  
Molecular Features ◽  
Therapy Choice ◽  
Next Generation Sequencing Ngs

Molecular diagnostics is a mandatory component of modern clinical oncology. The most known examples of molecular diagnostic procedures include the detection of hereditary cancer syndromes and the analysis of somatic drug-sensitizing mutations in protein kinases. Advances in cancer research as well as the development of new technologies led to emergence of new trends in this area of medicine. The invention of next generation sequencing (NGS) has a potential to dramatically change the landscape of molecular diagnostics. NGS allows to significantly improve the efficiency and availability of genetic testing for hereditary cancers as well as to undertake comprehensive tumor mutation profiling to guide the therapy choice. Tumors usually change their properties during therapeutic intervention. Monitoring of these properties is important for proper selection of further treatment options. So-called liquid biopsy is essential for this purpose, as it allows to detect key molecular features of the tumors by a non-invasive approach. There is an increasing popularity of ex vivo tumor models, which allow to cultivate tumor cells and to select the therapy based on the results of drug sensitivity tests.

Clinical utility and reimbursement for expanded genomic panel testing in adult oncology.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6593-6593 ◽  
Author(s):  
Susan Jean Hsiao ◽  
Anthony Sireci ◽  
Danielle Pendrick ◽  
Christopher Freeman ◽  
Jessica Yang ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Clinical Utility ◽  
Clinical Care ◽  
Treatment Options ◽  
Copy Number Variations ◽  
Genomic Testing ◽  
Prognostic Information ◽  
Multiple Tumor ◽  
Future Treatment ◽  
Panel Testing

6593 Background: The routine use of large next generation sequencing (NGS) cancer panels is required to identify the increasing number of, but often uncommon actionable alterations present across multiple tumor histologies to guide therapy. Inconsistent coverage and variable payment is hindering adoption of these tests into clinical practice. A review of clinical utility, coverage and reimbursement was conducted in a cohort of adult oncology patients who received expanded genomic panel testing as part of their clinical care. Methods: The Columbia Combined Cancer Panel (CCCP), a 467 gene panel designed to detect single nucleotide variants, indels, and copy number variations in solid and liquid tumors was performed in a CLIA-certified laboratory at Columbia University Irving Medical Center. Clinical utility categories included: immediate change in management; informed future treatment options; provided diagnostic/prognostic information; and other impact. Claims were submitted between 1/1/17 and 4/30/18. Carriers were categorized into commercial, managed-government, and government plans. Results: 300 tumors underwent NGS. Reimbursement data were available for 258 cases. 57% of testing was performed for a treatment-resistant, recurrent, or high stage cancer, or for a cancer of rare/mixed histology (21%). Findings were clinically actionable in 183 cases (61%). Results led to an immediate change in management (n = 6, 2%), informed future treatment options (n = 140, 47%), and provided diagnostic/prognostic information (n = 29, 10%). Only 57 tests (22%) received coverage. In 59% of denials (118/201), a clinically-actionable result was found. Commercial plans reimbursed 29/119 tests (24%) and managed-government plans reimbursed 28/54 tests (52%). Government plans provided no coverage for 85 tests. On average, insurers reimbursed 10% of the total CCCP service charges: 12.5% for commercial and 22% for managed-government plans. Conclusions: Expanded genomic testing identified clinically-impactful alterations in 61% of cases. Limited coverage and low reimbursement remain a barrier and broader reimbursement policies are needed to adopt expanded genomic testing that benefits patients into clinical practice.

Canadian Pain Society and Canadian Rheumatology Association Recommendations for Rational Care of Persons with Fibromyalgia. A Summary Report

2013 ◽  
Vol 40 (8) ◽  
pp. 1388-1393 ◽  
Author(s):  
Mary-Ann Fitzcharles ◽  
Peter A. Ste-Marie ◽  
Don L. Goldenberg ◽  
John X. Pereira ◽  
Susan Abbey ◽  
...  
Keyword(s):  
Clinical Judgment ◽  
Clinical Care ◽  
Treatment Options ◽  
Management Strategies ◽  
Evidence Based ◽  
Health Community ◽  
Life Pattern ◽  
New Treatment ◽  
Improved Function ◽  
Evidence Based Guidelines

Objective.To summarize the development of evidence-based guidelines for the clinical care of persons with fibromyalgia (FM), taking into account advances in understanding of the pathogenesis of FM, new diagnostic criteria, and new treatment options.Methods.Recommendations for diagnosis, treatment, and patient followup were drafted according to the classification system of the Oxford Centre for Evidence-Based Medicine, and following review were endorsed by the Canadian Rheumatology Association and the Canadian Pain Society.Results.FM is a polysymptomatic syndrome presenting a spectrum of severity, with a pivotal symptom of body pain. FM is a positive clinical diagnosis, not a diagnosis of exclusion, and not requiring specialist confirmation. There are no confirmatory laboratory tests, although some investigation may be indicated to exclude other conditions. Ideal care is in the primary care setting, incorporating nonpharmacologic and pharmacologic strategies in a multimodal approach with active patient participation. The treatment objective should be reduction of symptoms, but also improved function using a patient-tailored treatment approach that is symptom-based. Self-management strategies combining good lifestyle habits and fostering a strong locus of control are imperative. Medications afford only modest relief, with doses often lower than suggested, and drug combinations used according to clinical judgment. There is a need for continued reassessment of the risk-benefit ratio for any drug treatment. Outcome should be aimed toward functioning within a normal life pattern and any culture of disablement should be discouraged.Conclusion.These guidelines should provide the health community with reassurance for the global care of patients with FM with the aim of improving patient outcome by reducing symptoms and maintaining function.

External quality assessment (EQA) and alternative assessment procedures (AAPs) in molecular diagnostics: findings of an international survey

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Deborah A. Payne ◽  
Graciela Russomando ◽  
Mark W. Linder ◽  
Katarina Baluchova ◽  
Tester Ashavaid ◽  
...  
Keyword(s):  
Quality Assessment ◽  
Molecular Diagnostics ◽  
Alternative Assessment ◽  
External Quality Assessment ◽  
Clinical Chemistry ◽  
Molecular Diagnostic ◽  
Internal Quality ◽  
External Quality ◽  
Iso 15189 ◽  
Eqa Schemes

AbstractObjectivesQuality management for clinical laboratories requires the establishment of internal procedures including standard operating procedures (SOPs), internal quality control (QC), validation of test results and quality assessment. External quality assessment (EQA) and alternativeassessment procedures (AAPs) are part of the quality hierarchy required for diagnostic testing. The International Organization for Standardization (ISO) document with requirements for conformance ISO 15189 and the Clinical and Laboratory Standards Institute document (CLSI) QMS24 require participation in EQA schemes and AAPs where applicable. The purpose of this study was to perform a global survey of EQA and AAPs for key procedures in molecular diagnostic laboratories.MethodsThe Committee for Molecular Diagnostics of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC C-MD) conducted a survey of international molecular laboratories that covered specific topics of molecular diagnostic services as well as methods for EQA and AAPs. The survey addressed the following aspects: (1) usage of laboratory-developed test (LDT), (2) participation in EQA schemes and (3) performance of AAPs.ResultsA total of 93 responses from laboratories located in Asia, Europe, the Middle East, North America and South America were received. The majority of the participating laboratories (65.9%) use LDTs and 81.3% stated that it is mandatory for them to participate in EQA programs, while 22% of the laboratories reported not performing AAPs. Thirty-one percent of the laboratories use EQAs for fewer than 50.0% of their reported parameters/analytes.ConclusionsWhile the majority of laboratories perform EQA and AAPs to improve their quality in molecular diagnostics, the amount of AAPs as quality procedures differs within the laboratories. Further surveys are necessary to clarify the existing needs in additional EQAs and standardized AAPs. The survey will also guide future efforts of the IFCC C-MD for identifying quality practices in need to improve harmonization and standardization within molecular diagnostics.

scholarly journals Molecular Subtypes and Precision Oncology in Intrahepatic Cholangiocarcinoma

2021 ◽  
Vol 10 (13) ◽  
pp. 2803
Author(s):  
Carolin Czauderna ◽  
Martha M. Kirstein ◽  
Hauke C. Tews ◽  
Arndt Vogel ◽  
Jens U. Marquardt
Keyword(s):  
Clinical Care ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Specific Treatment ◽  
Growth Factor Receptor ◽  
Treatment Modalities ◽  
Precision Oncology ◽  
Recurrence Rates ◽  
Isocitrate Dehydrogenase 1 ◽  
Liver Cancers

Cholangiocarcinomas (CCAs) are the second-most common primary liver cancers. CCAs represent a group of highly heterogeneous tumors classified based on anatomical localization into intra- (iCCA) and extrahepatic CCA (eCCA). In contrast to eCCA, the incidence of iCCA is increasing worldwide. Curative treatment strategies for all CCAs involve oncological resection followed by adjuvant chemotherapy in early stages, whereas chemotherapy is administered at advanced stages of disease. Due to late diagnosis, high recurrence rates, and limited treatment options, the prognosis of patients remains poor. Comprehensive molecular characterization has further revealed considerable heterogeneity and distinct prognostic and therapeutic traits for iCCA and eCCA, indicating that specific treatment modalities are required for different subclasses. Several druggable alterations and oncogenic drivers such as fibroblast growth factor receptor 2 gene fusions and hotspot mutations in isocitrate dehydrogenase 1 and 2 mutations have been identified. Specific inhibitors have demonstrated striking antitumor activity in affected subgroups of patients in phase II and III clinical trials. Thus, improved understanding of the molecular complexity has paved the way for precision oncological approaches. Here, we outline current advances in targeted treatments and immunotherapeutic approaches. In addition, we delineate future perspectives for different molecular subclasses that will improve the clinical care of iCCA patients.

scholarly journals COVID-19: Before the Fall, An Evidence-Based Narrative Review of Treatment Options

2021 ◽  
Author(s):  
Nicholas Rebold ◽  
Dana Holger ◽  
Sara Alosaimy ◽  
Taylor Morrisette ◽  
Michael Rybak
Keyword(s):  
Treatment Options ◽  
Narrative Review ◽  
Evidence Based

scholarly journals Perspectives and experiences of patients and healthcare professionals with geriatric assessment in chronic kidney disease: a qualitative study

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Carlijn G. N. Voorend ◽  
Noeleen C. Berkhout-Byrne ◽  
Yvette Meuleman ◽  
Simon P. Mooijaart ◽  
Willem Jan W. Bos ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Qualitative Study ◽  
Clinical Outcomes ◽  
Geriatric Assessment ◽  
Clinical Care ◽  
Treatment Options ◽  
Routine Care ◽  
Treatment Team ◽  
Dutch Hospital ◽  
Additional Support

Abstract Background Older patients with end-stage kidney disease (ESKD) often live with unidentified frailty and multimorbidity. Despite guideline recommendations, geriatric assessment is not part of standard clinical care, resulting in a missed opportunity to enhance (clinical) outcomes including quality of life in these patients. To develop routine geriatric assessment programs for patients approaching ESKD, it is crucial to understand patients’ and professionals’ experiences with and perspectives about the benefits, facilitators and barriers for geriatric assessment. Methods In this qualitative study, semi-structured focus group discussions were conducted with ESKD patients, caregivers and professionals. Participants were purposively sampled from three Dutch hospital-based study- and routine care initiatives involving geriatric assessment for (pre-)ESKD care. Transcripts were analysed inductively using thematic analysis. Results In six focus-groups, participants (n = 47) demonstrated four major themes: (1) Perceived characteristics of the older (pre)ESKD patient group. Patients and professionals recognized increased vulnerability and (cognitive) comorbidity, which is often unrelated to calendar age. Both believed that often patients are in need of additional support in various geriatric domains. (2) Experiences with geriatric assessment. Patients regarded the content and the time spent on the geriatric assessment predominantly positive. Professionals emphasized that assessment creates awareness among the whole treatment team for cognitive and social problems, shifting the focus from mainly somatic to multidimensional problems. Outcomes of geriatric assessment were observed to enhance a dialogue on suitability of treatment options, (re)adjust treatment and provide/seek additional (social) support. (3) Barriers and facilitators for implementation of geriatric assessment in routine care. Discussed barriers included lack of communication about goals and interpretation of geriatric assessment, burden for patients, illiteracy, and organizational aspects. Major facilitators are good multidisciplinary cooperation, involvement of geriatrics and multidisciplinary team meetings. (4) Desired characteristics of a suitable geriatric assessment concerned the scope and use of tests and timing of assessment. Conclusions Patients and professionals were positive about using geriatric assessment in routine nephrology care. Implementation seems achievable, once barriers are overcome and facilitators are endorsed. Geriatric assessment in routine care appears promising to improve (clinical) outcomes in patients approaching ESKD.

scholarly journals Implementation of Rapid Molecular Diagnostic Tests and Antimicrobial Stewardship Involvement in Acute-Care Hospitals

2020 ◽  
Vol 41 (S1) ◽  
pp. s278-s279
Author(s):  
Maiko Kondo ◽  
Matthew Simon ◽  
Esther Babady ◽  
Angela Loo ◽  
David Calfee
Keyword(s):  
Antimicrobial Stewardship ◽  
Diagnostic Tests ◽  
New Technology ◽  
Clinical Care ◽  
Bloodstream Infections ◽  
Clinical Decision ◽  
Research Network ◽  
Molecular Diagnostic ◽  
Financial Outcomes ◽  
Stewardship Program

Background: In recent years, several rapid molecular diagnostic tests (RMDTs) for infectious diseases diagnostics, such as bloodstream infections (BSIs), have become available for clinical use. The extent to which RMDTs have been adopted and how the results of these tests have been incorporated into clinical care are currently unknown. Methods: We surveyed members of the Society for Healthcare Epidemiology of America Research Network to characterize utilization of RMDT in hospitals and antimicrobial stewardship program (ASP) involvement in result communication and interpretation. The survey was administered using Qualtrics software, and data were analyzed using Stata and Excel software. Results: Overall, 57 responses were received (response rate, 59%), and 72% were from academic hospitals; 50 hospitals (88%) used at least 1 RMDT for BSI (Fig. 1). The factors most commonly reported to have been important in the decision to adopt RMDT were improvements in antimicrobial usage (82%), clinical outcomes (74%), and laboratory efficiency (52%). Among 7 hospitals that did not use RMDT for BSI, the most common reason was cost of new technology. In 50 hospitals with RMDT for BSI, 54% provided written guidelines for optimization or de-escalation of antimicrobials based upon RMDT results. In 40 hospitals (80%), microbiology laboratories directly notified a healthcare worker of the RMDT results: 70% provided results to a physician, nurse practitioner, or physician assistant; 48% to the ASP team; and 33% to a nurse. Furthermore, 11 hospitals (22%) had neither guidelines nor ASP intervention. In addition, 24 hospitals (48%) reported performing postimplementation evaluation of RMDT impact. Reported findings included reduction in time to antibiotic de-escalation (75%), reduction in length of stay (25%), improved laboratory efficiency (20%), and reduction in mortality and overall costs (12%). Among the 47 hospitals with both RMDT and ASP, 79% reported that the ASP team routinely reviewed blood culture RMDT results, and 53.2% used clinical decision support software to do so. Finally, 53 hospitals (93%) used 1 or more RMDT for non–bloodstream infections (Fig. 1). Fewer than half of hospitals provided written guidelines to assist clinicians in interpreting these RMDT results. Conclusions: RMDTs have been widely adopted by participating hospitals and are associated with positive self-reported clinical, logistic, and financial outcomes. However, nearly 1 in 4 hospitals did not have guidelines or ASP interventions to assist clinicians with optimization of antimicrobial prescribing based on RMDT results for BSI. Also, most hospitals did not have guidelines for RMDT results for non-BSI. These findings suggest that opportunities exist to further enhance the potential benefits of RMDT.Funding: NoneDisclosures: None

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