Although the field of pharmacogenetics has existed for decades, the implementation of, pharmacogenetic testing in clinical care has been slow. There are numerous publications, describing the barriers to clinical implementation of pharmacogenetics. Recently, several freely, available resources have been developed to help address these barriers. In this review we, discuss current programs that use preemptive genotyping to optimize the pharmacotherapy of, patients. Array-based preemptive testing includes a large number of relevant pharmacogenes, that impact multiple high-risk drugs. Using a preemptive approach allows genotyping results to, be available prior to any prescribing decision so that genomic variation may be considered as, an inherent patient characteristic in the planning of therapy. This review describes the common, elements among programs that have implemented preemptive genotyping and highlights key, processes for implementation, including clinical decision support.

Objectives Medical errors and unanticipated negative patient outcomes can damage the well-being of healthcare providers. These affected individuals, referred to as “second victims,” can experience various psychological and physical symptoms. Support resources provided by healthcare organizations to prevent and reduce second victim–related harm are often inadequate. In this study, we present the development and psychometric evaluation of the Second Victim Experience and Support Tool (SVEST), a survey instrument that can assist healthcare organizations to implement and track the performance of second victim support resources. Methods The SVEST (29 items representing 7 dimensions and 2 outcome variables) was completed by 303 healthcare providers involved in direct patient care. The survey collected responses on second victim–related psychological and physical symptoms and the quality of support resources. Desirability of possible support resources was also measured. The SVEST was assessed for content validity, internal consistency, and construct validity with confirmatory factor analysis (CFA). Results CFA results suggested good model fit for the survey. Cronbach's alpha reliability scores for the survey dimensions ranged from 0.61 to 0.89. The most desired second victim support option was “A respected peer to discuss the details of what happened.” Conclusions The SVEST can be used by healthcare organizations to evaluate second victim experiences of their staff as well as the quality of existing support resources. It can also provide healthcare organization leaders with information on second victim–related support resources most preferred by their staff. The SVEST can be administered before and after implementing new second victim resources to measure perceptions of effectiveness.

INTRODUCTIONReporting and sharing pharmacogenetic test results across clinical laboratories and electronic health records is a crucial step toward the implementation of clinical pharmacogenetics, but allele function and phenotype terms are not standardized. Our goal was to develop terms that can be broadly applied to characterize pharmacogenetic allele function and inferred phenotypes.MATERIALS AND METHODSTerms currently used by genetic testing laboratories and in the literature were identified. The Clinical Pharmacogenetics Implementation Consortium (CPIC) used the Delphi method to obtain consensus and agree on uniform terms among pharmacogenetic experts.RESULTSExperts with diverse involvement in at least one area of pharmacogenetics (clinicians, researchers, genetic testing laboratorians, pharmacogenetics implementers, and clinical informaticians; n=58) participated. After completion of five surveys, consensus (>70%) was reached with 90% of experts agreeing to the final sets of pharmacogenetic terms.DISCUSSIONThe proposed standardized pharmacogenetic terms will improve the understanding and interpretation of pharmacogenetic tests and reduce confusion by maintaining consistent nomenclature. These standard terms can also facilitate pharmacogenetic data sharing across diverse electronic health care record systems with clinical decision support.

The Clinical Pharmacogenetics Implementation Consortium (CPIC) publishes genotype-based drug guidelines to help clinicians understand how available genetic test results could be used to optimize drug therapy. CPIC has focused initially on well-known examples of pharmacogenomic associations that have been implemented in selected clinical settings, publishing nine to date. Each CPIC guideline adheres to a standardized format and includes a standard system for grading levels of evidence linking genotypes to phenotypes and assigning a level of strength to each prescribing recommendation. CPIC guidelines contain the necessary information to help clinicians translate patient-specific diplotypes for each gene into clinical phenotypes or drug dosing groups. This paper reviews the development process of the CPIC guidelines and compares this process to the Institute of Medicine’s Standards for Developing Trustworthy Clinical Practice Guidelines.

Pharmacogenetics is frequently cited as an area for initial focus of the clinical implementation of genomics. Through the PG4KDS protocol, St. Jude Children’s Research Hospital pre-emptively genotypes patients for 230 genes using the Affymetrix Drug Metabolizing Enzymes and Transporters (DMET) Plus array supplemented with a CYP2D6 copy number assay. The PG4KDS protocol provides a rational, stepwise process for implementing gene/drug pairs, organizing data, and obtaining consent from patients and families. Through August 2013, 1559 patients have been enrolled, and 4 gene tests have been released into the electronic health record (EHR) for clinical implementation: TPMT, CYP2D6, SLCO1B1, and CYP2C19. These genes are coupled to 12 high-risk drugs. Of the 1016 patients with genotype test results available, 78% of them had at least one high-risk (i.e., actionable) genotype result placed in their EHR. Each diplotype result released to the EHR is coupled with an interpretive consult that is created in a concise, standardized format. To support-gene based prescribing at the point of care, 55 interruptive clinical decision support (CDS) alerts were developed. Patients are informed of their genotyping result and its relevance to their medication use through a letter. Key elements necessary for our successful implementation have included strong institutional support, a knowledgeable clinical laboratory, a process to manage any incidental findings, a strategy to educate clinicians and patients, a process to return results, and extensive use of informatics, especially CDS. Our approach to pre-emptive clinical pharmacogenetics has proven feasible, clinically useful, and scalable.

Biologics are essential to oncology care. As patents for older biologics begin to expire, the United States is developing an abbreviated regulatory process for the approval of similar biologics (biosimilars), which raises important considerations for the safe and appropriate incorporation of biosimilars into clinical practice for patients with cancer. The potential for biosimilars to reduce the cost of biologics, which are often high-cost components of oncology care, was the impetus behind the Biologics Price Competition and Innovation Act of 2009, a part of the 2010 Affordable Care Act. In March 2011, NCCN assembled a work group consisting of thought leaders from NCCN Member Institutions and other organizations, to provide guidance regarding the challenges health care providers and other key stakeholders face in incorporating biosimilars in health care practice. The work group identified challenges surrounding biosimilars, including health care provider knowledge, substitution practices, pharmacovigilance, naming and product tracking, coverage and reimbursement, use in off-label settings, and data requirements for approval.

Background Second victim experiences can affect the well-being of healthcare providers and compromise patient safety. Many factors associated with improved coping afer patient safety event involvement are also components of a strong patient safety culture, so that supportive patient safety cultures may reduce second victim–related trauma. A cross-sectional survey study was conducted to assess the influence of patient safety culture on second victim–related distress, in which associations among patient safety culture dimensions, organizational support, and second victim distress were investigated. Methods The Agency for Healthcare Research and Quality (AHRQ) Hospital Survey on Patient Safety Culture (HSOPSC) and the Second Victim Experience and Support Tool (SVEST), which was developed to assess organizational support and personal and professional distress after involvement in a patient safety event, were administered to nurses involved in direct patient care. Results Of 358 nurses, 155 (41%) responded, of whom 144 completed both surveys. Hierarchical linear regression demonstrated that the patient safety culture survey dimension nonpunitive response to errors was significantly associated with reductions in the second victim survey dimensions psychological, physical, and professional distress (p <.001). As a mediator, organizational support fully explained the nonpunitive response to errors–physical distress and nonpunitive response to errors–professional distress relationships and partially explained the nonpunitive response to error–psychological distress relationship. Conclusions A nonpunitive response to errors may mitigate the negative effects of involvement in a patient safety event by encouraging supportive interactions. Also, perceptions of second victim–related distress may be less severe when hospital cultures are characterized by nonpunitive response to errors. Reducing punitive response to error and encouraging supportive coworker, supervisor, and institutional interactions may be useful strategies to manage the severity of second victim experiences.

BackgroundActive clinical decision support (CDS) delivered through an electronic health record (EHR) facilitates gene-based drug prescribing and other applications of genomics to patient care.ObjectiveWe describe the development, implementation, and evaluation of active CDS for multiple pharmacogenetic test results reported preemptively.Materials and methodsClinical pharmacogenetic test results accompanied by clinical interpretations are placed into the patient's EHR, typically before a relevant drug is prescribed. Problem list entries created for high-risk phenotypes provide an unambiguous trigger for delivery of post-test alerts to clinicians when high-risk drugs are prescribed. In addition, pre-test alerts are issued if a very-high risk medication is prescribed (eg, a thiopurine), prior to the appropriate pharmacogenetic test result being entered into the EHR. Our CDS can be readily modified to incorporate new genes or high-risk drugs as they emerge.ResultsThrough November 2012, 35 customized pharmacogenetic rules have been implemented, including rules for TPMT with azathioprine, thioguanine, and mercaptopurine, and for CYP2D6 with codeine, tramadol, amitriptyline, fluoxetine, and paroxetine. Between May 2011 and November 2012, the pre-test alerts were electronically issued 1106 times (76 for thiopurines and 1030 for drugs metabolized by CYP2D6), and the post-test alerts were issued 1552 times (1521 for TPMT and 31 for CYP2D6). Analysis of alert outcomes revealed that the interruptive CDS appropriately guided prescribing in 95% of patients for whom they were issued.ConclusionsOur experience illustrates the feasibility of developing computational systems that provide clinicians with actionable alerts for gene-based drug prescribing at the point of care.