Pitfalls and challenges in genetic test interpretation: An exploration of genetic professionals experience with interpretation of results.
Ontology highlight
ABSTRACT:
SUBMITTER: Donohue KE
PROVIDER: S-EPMC8489659 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Direct-to-consumer genetic testing (DTC-GT) allows individuals to obtain genetic tests directly from companies without necessarily involving health professionals. This study explores genetic health professionals' opinions of health-related DTC-GT and the reported frequency of individuals presenting to clinical genetics services after undertaking testing. Genetic counsellors and clinical geneticists, members of the Human Genetics Society of Australasia, completed an online survey in mid 2011. The 130 genetic counsellors (estimated response fraction=43%) and 38 clinical geneticists (estimated response fraction=46%) had mixed opinions regarding DTC-GT, with only 7% confident in accurately interpreting and explaining DTC-GT results. Nineteen respondents (11%) reported one or more client(s) referred to them after undertaking DTC-GT. Descriptions of 25 clients were extracted from responses, and respondents reported that all clients were concerned for the health of either themselves or family members. Most clients presented to genetic clinics specifically as a result of their DTC-GT (96%) and were self or GP referred (92%). Respondents perceived that their clients typically undertook DTC-GT because they wanted to identify monogenic conditions, including carrier testing and/or know their susceptibility or predisposition for complex conditions (88%). The majority of clients needed help interpreting DTC-GT results (80%), however in general were not questioning the validity of their DTC-GT results (92%) nor seeking further genetic testing (84%). Currently, DTC-GT is not a major reason for referral to clinical genetics services in Australia and New Zealand and the majority of genetic health professionals lack confidence in being able to accurately interpret and explain DTC-GT results.
| S-EPMC3400727 | biostudies-literature
Project description:In spite of a greatly reduced incidence rate due to vaccination, mumps outbreaks continue to occur in several areas of the world, sometimes in vaccinated populations. This article describes an outbreak in a highly vaccinated population in southwestern Ontario, Canada, and the challenges encountered in interpreting the results of diagnostic tests used in the outbreak. During the outbreak, patients were interviewed and classified according to the outbreak case definition, and specimens were collected for diagnostic testing according to Ontario guidelines. Twenty-seven individuals were classified as confirmed cases (n = 19) or suspect cases (n = 8) according to the case definition, only 9 of which were laboratory-confirmed cases: 7 confirmed by reverse transcriptase PCR (RT-PCR) and 2 by IgM serology. All 19 confirmed cases represented patients who were associated with secondary schools in the local area and had been vaccinated against mumps with one (n = 2) or two (n = 17) doses of the measles-mumps-rubella (MMR) vaccine. This is the first published report of an outbreak of mumps in Ontario in which all confirmed cases had been vaccinated against the disease. It highlights the limitations of and difficulties in interpreting current mumps diagnostic tests when used in vaccinated individuals.
| S-EPMC5299122 | biostudies-literature
Project description:There are several methods to read skin prick test results in type-I allergy testing. A commonly used method is to characterize the wheal size by its 'average diameter'. A more accurate method is to scan the area of the wheal to calculate the actual size. In both methods, skin prick test (SPT) results can be corrected for histamine-sensitivity of the skin by dividing the results of the allergic reaction by the histamine control. The objectives of this study are to compare different techniques of quantifying SPT results, to determine a cut-off value for a positive SPT for histamine equivalent prick -index (HEP) area, and to study the accuracy of predicting cashew nut reactions in double-blind placebo-controlled food challenge (DBPCFC) tests with the different SPT methods.Data of 172 children with cashew nut sensitisation were used for the analysis. All patients underwent a DBPCFC with cashew nut. Per patient, the average diameter and scanned area of the wheal size were recorded. In addition, the same data for the histamine-induced wheal were collected for each patient. The accuracy in predicting the outcome of the DBPCFC using four different SPT readings (i.e. average diameter, area, HEP-index diameter, HEP-index area) were compared in a Receiver-Operating Characteristic (ROC) plot.Characterizing the wheal size by the average diameter method is inaccurate compared to scanning method. A wheal average diameter of 3 mm is generally considered as a positive SPT cut-off value and an equivalent HEP-index area cut-off value of 0.4 was calculated. The four SPT methods yielded a comparable area under the curve (AUC) of 0.84, 0.85, 0.83 and 0.83, respectively. The four methods showed comparable accuracy in predicting cashew nut reactions in a DBPCFC.The 'scanned area method' is theoretically more accurate in determining the wheal area than the 'average diameter method' and is recommended in academic research. A HEP-index area of 0.4 is determined as cut-off value for a positive SPT. However, in clinical practice, the 'average diameter method' is also useful, because this method provides similar accuracy in predicting cashew nut allergic reactions in the DBPCFC.Trial number NTR3572.
| S-EPMC4763448 | biostudies-other
Project description: Not available
| S-EPMC6224793 | biostudies-literature
Project description:BACKGROUND:Genomic testing is increasingly performed in oncology, but concerns remain regarding the clinician's ability to interpret results. In the current study, the authors sought to determine the agreement between physicians and genomic annotators from the Precision Oncology Decision Support (PODS) team at The University of Texas MD Anderson Cancer Center in Houston regarding actionability and the clinical use of test results. METHODS:On a prospective protocol, patients underwent clinical genomic testing for hotspot mutations in 46 or 50 genes. Six months after sequencing, physicians received questionnaires for patients who demonstrated a variant in an actionable gene, investigating their perceptions regarding the actionability of alterations and clinical use of these findings. Genomic annotators independently classified these variants as actionable, potentially actionable, unknown, or not actionable. RESULTS:Physicians completed 250 of 288 questionnaires (87% response rate). Physicians considered 168 of 250 patients (67%) as having an actionable alteration; of these, 165 patients (98%) were considered to have an actionable alteration by the PODS team and 3 were of unknown significance. Physicians were aware of genotype-matched therapy available for 119 patients (71%) and 48 of these 119 patients (40%) received matched therapy. Approximately 46% of patients in whom physicians regarded alterations as not actionable (36 of 79 patients) were classified as having an actionable/potentially actionable mutation by the PODS team. However, many of these were only theoretically actionable due to limited trials and/or therapies (eg, KRAS). CONCLUSIONS:Physicians are aware of recurrent mutations in actionable genes on "hotspot" panels. As larger genomic panels are used, there may be a growing need for annotation of actionability. Decision support to increase awareness of genomically relevant trials and novel treatment options for recurrent mutations (eg, KRAS) also are needed. Cancer 2018;124:966-72. © 2017 American Cancer Society.
| S-EPMC5821595 | biostudies-literature
Project description:Genetic testing of cancer susceptibility genes is now widely applied in clinical practice to predict risk of developing cancer. In general, sequence-based testing of germline DNA is used to determine whether an individual carries a change that is clearly likely to disrupt normal gene function. Genetic testing may detect changes that are clearly pathogenic, clearly neutral, or variants of unclear clinical significance. Such variants present a considerable challenge to the diagnostic laboratory and the receiving clinician in terms of interpretation and clear presentation of the implications of the result to the patient. There does not appear to be a consistent approach to interpreting and reporting the clinical significance of variants either among genes or among laboratories. The potential for confusion among clinicians and patients is considerable and misinterpretation may lead to inappropriate clinical consequences. In this article we review the current state of sequence-based genetic testing, describe other standardized reporting systems used in oncology, and propose a standardized classification system for application to sequence-based results for cancer predisposition genes. We suggest a system of five classes of variants based on the degree of likelihood of pathogenicity. Each class is associated with specific recommendations for clinical management of at-risk relatives that will depend on the syndrome. We propose that panels of experts on each cancer predisposition syndrome facilitate the classification scheme and designate appropriate surveillance and cancer management guidelines. The international adoption of a standardized reporting system should improve the clinical utility of sequence-based genetic tests to predict cancer risk.
| S-EPMC3075918 | biostudies-literature
Project description:Family physicians (FPs) will encounter genetic concerns within community practice. To determine how FPs compare to genetic counselors (GCs), a cross-sectional survey was distributed to Canadian FPs and GCs in 2019. The survey assessed risk analysis, counseling, and management of genetic information. FPs performed less well than GCs on each survey question and scenario (p < 0.05). Average overall survey scores for FPs were lower than GCs (62% vs. 93%, p < 0.001). Additional genetic training for FPs may help avoid potential harm.
| S-EPMC8241956 | biostudies-literature
Project description:BACKGROUND:Precision medicine is set to deliver a rich new data set of genomic information. However, the number of certified specialists in the United States is small, with only 4244 genetic counselors and 1302 clinical geneticists. We conducted a national survey of 264 medical professionals to evaluate how they interpret genetic test results, determine their confidence and self-efficacy of interpreting genetic test results with patients, and capture their opinions and experiences with direct-to-consumer genetic tests (DTC-GT). METHODS:Participants were grouped into two categories, genetic specialists (genetic counselors and clinical geneticists) and medical providers (primary care, internists, physicians assistants, advanced nurse practitioners, etc.). The survey (full instrument can be found in the Additional file 1) presented three genetic test report scenarios for interpretation: a genetic risk for diabetes, genomic sequencing for symptoms report implicating a potential HMN7B: distal hereditary motor neuropathy VIIB diagnosis, and a statin-induced myopathy risk. Participants were also asked about their opinions on DTC-GT results and rank their own perceived level of preparedness to review genetic test results with patients. RESULTS:The rates of correctly interpreting results were relatively high (74.4% for the providers compared to the specialist's 83.4%) and age, prior genetic test consultation experience, and level of trust assigned to the reports were associated with higher correct interpretation rates. The self-selected efficacy and the level of preparedness to consult on a patient's genetic results were higher for the specialists than the provider group. CONCLUSION:Specialists remain the best group to assist patients with DTC-GT, however, primary care providers may still provide accurate interpretation of test results when specialists are unavailable.
| S-EPMC6876107 | biostudies-literature
Project description:BackgroundIn some healthcare systems, it is common that patients address laboratory test centers directly without a physician's recommendation. This practice is widely spread in Russia with about 28% of patients who visiting laboratory test centers for diagnostics. This causes an issue when patients get no help from the physician in understanding the results. Computer decision support systems proved to efficiently solve a resource consuming task of interpretation of the test results. So, a decision support system can be implemented to rise motivation and empower the patients who visit a laboratory service without a doctor's referral.MethodsWe have developed a clinical decision support system for patients that solves a classification task and finds a set of diagnoses for the provided laboratory tests results. The Wilson and Lankton's assessment model was applied to measure patients' acceptance of the solution.ResultsA first order predicates-based decision support system has been implemented to analyze laboratory test results and deliver reports in natural language to patients. The evaluation of the system showed a high acceptance of the decision support system and of the reports that it generates.ConclusionsDetailed notification of the laboratory service patients with elements of the decision support is significant for the laboratory data management, and for patients' empowerment and safety.
| S-EPMC6053711 | biostudies-literature
Project description:BackgroundTesting for 'recent HIV infection' is common in surveillance, where only population-level estimates (of incidence) are reported. Typically, 'recent infection' is a category, obtained by applying a threshold on an underlying continuous biomarker from some laboratory assay(s). Interpreting the biomarker values obtained for individual subjects, as estimates of the date of infection, has obvious potential applications in the context of studies of early infection, and has also for some years attracted significant interest as an extra component of post-test counselling and treatment initiation. The applicable analyses have typically run aground on the complexity of the full biomarker growth model, which is in principle a non-linear mixed-effects model of unknown structure, the fitting of which seems infeasible from realistically obtainable data.MethodsIt is known that to estimate Mean Duration of Recent Infection (MDRI) at a given value of the recent/non-recent -infection discrimination threshold, one may compress the full biomarker growth model into a relation capturing the probability of a recent test result as a function of time t since infection, given a value of assay threshold h which defines the recent/non-recent discrimination. We demonstrate that the derivative (gradient), with respect to h. of the probability of recent infection, seen as a function of both t and h, is identical to the formal likelihood relevant to Bayesian inference of the time since seroconversion, for a subject yielding an assay result h, at or close to the date of their first positive HIV test. This observation bypasses the need for fitting a complex detailed biomarker growth model. Using publicly available data from the CEPHIA collaboration, we calibrated this likelihood function for the Sedia Lag assay, and performed Bayesian inference on hypothetical infection data.ResultsWe demonstrate the generation of posteriors for infection date, for patients with various delays between their last negative and first positive HIV test, and a range of LAg assay results (ODn) hypothetically obtained on the date of the first positive result.ConclusionDepending on the last-negative / first-positive interval, there is a range of ODn values that yields posteriors significantly different from the uniform prior one would be left with based merely on interval censoring. Hence, a LAg ODn obtained on the date of, or soon after, diagnosis contains potentially significant information about infection dating. It seems worth analysing other assays with meaningful dynamic range, especially tests already routinely used in primary HIV diagnosis (for example chemiluminescent assays and reader/cartridge lateral flow tests which admit objective variable line intensity readings) which have a sufficient dynamic range that corresponds to a clinically meaningful range of times-since-infection that are worth distinguishing from each other.
| S-EPMC9333292 | biostudies-literature