Multi-gene Pharmacogenomic Testing That Includes Decision-Support Tools to Guide Medication Selection for Major Depression: A Health Technology Assessment.
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ABSTRACT:
SUBMITTER: Ontario Health (Quality)
PROVIDER: S-EPMC8382305 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundTreatment in bipolar disorder (BD) is commonly applied as a multimodal therapy based on decision algorithms that lack an integrative understanding of molecular mechanisms or a biomarker associated clinical outcome measure. Pharmacogenetics/genomics study the individual genetic variation associated with drug response. This selective review of pharmacogenomics and pharmacogenomic testing (PGT) in BD will focus on candidate genes and genome wide association studies of pharmacokinetic drug metabolism and pharmacodynamic drug response/adverse event, and the potential role of decision support tools that incorporate multiple genotype/phenotype drug recommendations.Main bodyWe searched PubMed from January 2013 to May 2019, to identify studies reporting on BD and pharmacogenetics, pharmacogenomics and PGT. Studies were selected considering their contribution to the field. We summarize our findings in: targeted candidate genes of pharmacokinetic and pharmacodynamic pathways, genome-wide association studies and, PGT platforms, related to BD treatment. This field has grown from studies of metabolizing enzymes (i.e., pharmacokinetics) and drug transporters (i.e., pharmacodynamics), to untargeted investigations across the entire genome with the potential to merge genomic data with additional biological information.ConclusionsThe complexity of BD genetics and, the heterogeneity in BD drug-related phenotypes, are important considerations for the design and interpretation of BD PGT. The clinical applicability of PGT in psychiatry is in its infancy and is far from reaching the robust impact it has in other medical disciplines. Nonetheless, promising findings are discovered with increasing frequency with remarkable relevance in neuroscience, pharmacology and biology.
| S-EPMC7338319 | biostudies-literature
Project description:The objective of this study was to evaluate the potential benefit of utilizing a pharmacogenomic testing report to guide the selection and dosing of psychotropic medications in an outpatient psychiatric practice. The non-randomized, open label, prospective cohort study was conducted from September 2009 to July 2010. In the first cohort, depressed patients were treated without the benefit of pharmacogenomic testing (the unguided group). A DNA sample was obtained from patients in the unguided group, but the results were not shared with either the physicians or patients until the end of the 8-week study period. In the second cohort (the guided group), testing results were provided at the beginning of the 8-week treatment period. Depression ratings were collected at baseline and after 2 weeks, 4 weeks and 8 weeks of treatment using the Quick Inventory of Depressive Symptomatology, Clinician Rated (QIDS-C16) and the 17-item Hamilton Rating Scale for Depression (HAM-D17). Clinician and patient satisfaction was also assessed. The reduction in depressive symptoms achieved within the guided treatment group was greater than the reduction of depressive symptoms in the unguided treatment group using either the QIDS-C16 (P=0.002) or HAM-D17 (P=0.04). We concluded that a rapidly available pharmacogenomic interpretive report provided clinical guidance that was associated with improved clinical outcomes for depressed patients treated in an outpatient psychiatric clinic setting.
| S-EPMC3565829 | biostudies-other
Project description:Clinicians still employ a "trial-and-error" approach to optimizing treatment regimens for late-life depression (LLD). With LLD affecting a significant and growing segment of the population, and with only about half of older adults responsive to antidepressant therapy, there is an urgent need for a better treatment paradigm. Pharmacogenetic decision support tools (DSTs), which are emerging technologies that aim to provide clinically actionable information based on a patient's genetic profile, offer a promising solution. Dozens of DSTs have entered the market in the past 15 years, but with varying level of empirical evidence to support their value. In this clinical review, we provide a critical analysis of the peer-reviewed literature on DSTs for major depression management. We then discuss clinical considerations for the use of these tools in treating LLD, including issues related to test interpretation, timing, and patient perspectives. In adult populations, newer generation DSTs show promise for the treatment of major depression. However, there are no primary clinical trials in LLD cohorts. Independent and comparative clinical trials are needed.
| S-EPMC5812821 | biostudies-literature
Project description:The effectiveness of selective serotonin reuptake inhibitors (SSRIs) in patients with major depressive disorder (MDD) is controversial.The clinical outcomes of subjects with nonpsychotic MDD were reported and compared with the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study outcomes to provide guidance on the effectiveness of SSRIs.Subjects were treated with citalopram/escitalopram for up to 8 weeks. Depression was measured using the Quick Inventory of Depressive Symptomatology-Clinician Rated (QIDS-C16) and the 17-item Hamilton Depression Rating Scale.The group of subjects with at least 1 follow-up visit had a remission (QIDS-C16 ? 5) rate of 45.8% as well as a response (50% reduction in QIDS-C16) rate of 64.8%, and 79.9% achieved an improvement of 5 points or higher in QIDS-C16 score. The Pharmacogenomic Research Network Antidepressant Medication Pharmacogenomic Study subjects were more likely to achieve a response than STAR*D study subjects. After adjustment for demographic factors, the response rates were not significantly different. When reporting the adverse effect burden, 60.5% of the subjects reported no impairment, 31.7% reported a minimal-to-mild impairment, and 7.8% reported a moderate-to-severe burden at the 4-week visit.Patients contemplating initiating an SSRI to treat their MDD can anticipate a high probability of symptom improvement (79.9%) with a low probability that their symptoms will become worse. Patients with lower baseline severity have a higher probability of achieving remission. The Pharmacogenomic Research Network Antidepressant Medication Pharmacogenomic Study replicates many findings of the first phase of the STAR*D study after controlling for the differences between the studies.
| S-EPMC3992481 | biostudies-literature
Project description:Poor adherence is associated with worse disease outcomes. Pharmacogenomics provides a possible intervention to address adherence. We hypothesized that pharmacogenomic-informed care could increase adherence. Patients in a prospective case-control study underwent preemptive pharmacogenomic genotyping with results available for provider use at the point of care; controls (not genotyped) were treated by the same providers. Over 6,000 e-prescriptions for 39 medications with actionable pharmacogenomic information were analyzed. Composite adherence, measured by modified proportion of days covered (mPDC), was compared between cases/controls and genomically concordant vs. genomically higher-risk medications. Overall, 536 patients were included. No difference in mean mPDC was observed due to availability of pharmacogenomic guidance. However, case patients prescribed high-risk pharmacogenomic medications were more than twice as likely to have low mPDC for these medications compared with genomically concordant prescriptions (odds ratio = 2.4 (1.03-5.74), P < 0.05). This study is the first to show that composite pharmacogenomic information predicts adherence.
| S-EPMC7363565 | biostudies-literature
Project description:Spatial management is a valuable strategy to advance regional goals for nature conservation, economic development, and human health. One challenge of spatial management is navigating the prioritization of multiple features. This challenge becomes more pronounced in dynamic management scenarios, in which boundaries are flexible in space and time in response to changing biological, environmental, or socioeconomic conditions. To implement dynamic management, decision-support tools are needed to guide spatial prioritization as feature distributions shift under changing conditions. Marxan is a widely applied decision-support tool designed for static management scenarios, but its utility in dynamic management has not been evaluated. EcoCast is a new decision-support tool developed explicitly for the dynamic management of multiple features, but it lacks some of Marxan's functionality. We used a hindcast analysis to compare the capacity of these 2 tools to prioritize 4 marine species in a dynamic management scenario for fisheries sustainability. We successfully configured Marxan to operate dynamically on a daily time scale to resemble EcoCast. The relationship between EcoCast solutions and the underlying species distributions was more linear and less noisy, whereas Marxan solutions had more contrast between waters that were good and poor to fish. Neither decision-support tool clearly outperformed the other; the appropriateness of each depends on management purpose, resource-manager preference, and technological capacity of tool developers. Article impact statement: Marxan can function as a decision-support tool for dynamic management scenarios in which boundaries are flexible in space and time.
| S-EPMC7317865 | biostudies-literature
Project description:Pharmacogenomic (PGx) testing is gaining recognition from physicians, pharmacists and patients as a tool for evidence-based medication management. However, seemingly similar PGx testing panels (and PGx-based decision support tools) can diverge in their technological specifications, as well as the genetic factors that determine test specificity and sensitivity, and hence offer different values for users. Reluctance to embrace PGx testing is often the result of unfamiliarity with PGx technology, a lack of knowledge about the availability of curated guidelines/evidence for drug dosing recommendations, and an absence of wide-spread institutional implementation efforts and educational support. Demystifying an often confusing and variable PGx marketplace can lead to greater acceptance of PGx as a standard-of-care practice that improves drug outcomes and provides a lifetime value for patients. Here, we highlight the key underlying factors of a PGx test that should be considered, and discuss the current progress of PGx implementation.
| S-EPMC6133969 | biostudies-literature
Project description:BACKGROUND:Decisional tools have demonstrated their importance in informing manufacturing and commercial decisions in the monoclonal antibody domain. Recent approved therapies in regenerative medicine have shown great clinical benefits to patients. OBJECTIVE:The objective of this review was to investigate what decisional tools are available and what issues and gaps have been raised for their use in regenerative medicine. METHODS:We systematically searched MEDLINE to identify articles on decision support tools relevant to tissue engineering, and cell and gene therapy, with the aim of identifying gaps for future decisional tool development. We included published studies in English including a description of decisional tools in regenerative medicines. We extracted data using a predesigned Excel table and assessed the data both quantitatively and qualitatively. RESULTS:We identified 9 articles addressing key decisions in manufacturing and product development challenges in cell therapies. The decision objectives, parameters, assumptions, and solution methods were analyzed in detail. We found that all decisional tools focused on cell therapies, and 6 of the 9 reviews focused on allogeneic cell therapy products. We identified no available tools on tissue-engineering and gene therapy products. These studies addressed key decisions in manufacturing and product development challenges in cell therapies, such as choice of technology, through modeling. CONCLUSIONS:Our review identified a limited number of decisional tools. While the monoclonal antibodies and biologics decisional tool domain has been well developed and has shown great importance in driving more cost-effective manufacturing processes and better investment decisions, there is a lot to be learned in the regenerative medicine domain. There is ample space for expansion, especially with regard to autologous cell therapies, tissue engineering, and gene therapies. To consider the problem more comprehensively, the full needle-to-needle process should be modeled and evaluated.
| S-EPMC6315273 | biostudies-literature
Project description:ObjectivesMedication reconciliation (MedRec) is essential for reducing patient harm caused by medication discrepancies across care transitions. Electronic support has been described as a promising approach to moving MedRec forward. We systematically reviewed the evidence about electronic tools that support MedRec, by (a) identifying tools; (b) summarizing their characteristics with regard to context, tool, implementation, and evaluation; and (c) summarizing key messages for successful development and implementation.Materials and methodsWe searched PubMed, the Cumulative Index to Nursing and Allied Health Literature, Embase, PsycINFO, and the Cochrane Library, and identified additional reports from reference lists, reviews, and patent databases. Reports were included if the electronic tool supported medication history taking and the identification and resolution of medication discrepancies. Two researchers independently selected studies, evaluated the quality of reporting, and extracted data.ResultsEighteen reports relative to 11 tools were included. There were eight quality improvement projects, five observational effectiveness studies, three randomized controlled trials (RCTs) or RCT protocols (ie, descriptions of RCTs in progress), and two patents. All tools were developed in academic environments in North America. Most used electronic data from multiple sources and partially implemented functionalities considered to be important. Relevant information on functionalities and implementation features was frequently missing. Evaluations mainly focused on usability, adherence, and user satisfaction. One RCT evaluated the effect on potential adverse drug events.ConclusionSuccessful implementation of electronic tools to support MedRec requires favorable context, properly designed tools, and attention to implementation features. Future research is needed to evaluate the effect of these tools on the quality and safety of healthcare.
| S-EPMC7654089 | biostudies-literature
Project description:Electronic prescribing is increasingly used, in part because of government incentives for its use. Many of its benefits come from clinical decision support (CDS), but often too many alerts are displayed, resulting in alert fatigue.To characterize the override rates for medication-related CDS alerts in the outpatient setting, the reasons cited for overrides at the time of prescribing, and the appropriateness of overrides.We measured CDS alert override rates and the coded reasons for overrides cited by providers at the time of prescribing. Our primary outcome was the rate of CDS alert overrides; our secondary outcomes were the rate of overrides by alert type, reasons cited for overrides at the time of prescribing, and override appropriateness for a subset of 600 alert overrides. Through detailed chart reviews of alert override cases, and selective literature review, we developed appropriateness criteria for each alert type, which were modified iteratively as necessary until consensus was reached on all criteria.We reviewed 157,483 CDS alerts (7.9% alert rate) on 2,004,069 medication orders during the study period. 82,889 (52.6%) of alerts were overridden. The most common alerts were duplicate drug (33.1%), patient allergy (16.8%), and drug-drug interactions (15.8%). The most likely alerts to be overridden were formulary substitutions (85.0%), age-based recommendations (79.0%), renal recommendations (78.0%), and patient allergies (77.4%). An average of 53% of overrides were classified as appropriate, and rates of appropriateness varied by alert type (p<0.0001) from 12% for renal recommendations to 92% for patient allergies.About half of CDS alerts were overridden by providers and about half of the overrides were classified as appropriate, but the likelihood of overriding an alert varied widely by alert type. Refinement of these alerts has the potential to improve the relevance of alerts and reduce alert fatigue.
| S-EPMC3994856 | biostudies-other