Browsing by Author "Blake, Kathryn V."
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Item Best-worst scaling methodology to evaluate constructs of the Consolidated Framework for Implementation Research: application to the implementation of pharmacogenetic testing for antidepressant therapy.(BMC, 2022-05-14) Salloum, Ramzi G.; Bishop, Jeffrey R.; Elchynski, Amanda L.; Smith, D. Max; Rowe, Elizabeth; Blake, Kathryn V.; Limdi, Nita A.; Aquilante, Christina L.; Bates, Jill; Beitelshees, Amber L.; Cipriani, Amber; Duong, Benjamin Q.; Empey, Philip E.; Formea, Christine M.; Hicks, J. Kevin; Mroz, Pawel; Oslin, David; Pasternak, Amy L.; Petry, Natasha; Ramsey, Laura B.; Schlichte, Allyson; Swain, Sandra M.; Ward, Kristen M.; Wiisanen, Kristin; Skaar, Todd C.; Van Driest, Sara L.; Cavallari, Larisa H.; Tuteja, SonyBACKGROUND: Despite the increased demand for pharmacogenetic (PGx) testing to guide antidepressant use, little is known about how to implement testing in clinical practice. Best-worst scaling (BWS) is a stated preferences technique for determining the relative importance of alternative scenarios and is increasingly being used as a healthcare assessment tool, with potential applications in implementation research. We conducted a BWS experiment to evaluate the relative importance of implementation factors for PGx testing to guide antidepressant use. METHODS: We surveyed 17 healthcare organizations that either had implemented or were in the process of implementing PGx testing for antidepressants. The survey included a BWS experiment to evaluate the relative importance of Consolidated Framework for Implementation Research (CFIR) constructs from the perspective of implementing sites. RESULTS: Participating sites varied on their PGx testing platform and methods for returning recommendations to providers and patients, but they were consistent in ranking several CFIR constructs as most important for implementation: patient needs/resources, leadership engagement, intervention knowledge/beliefs, evidence strength and quality, and identification of champions. CONCLUSIONS: This study demonstrates the feasibility of using choice experiments to systematically evaluate the relative importance of implementation determinants from the perspective of implementing organizations. BWS findings can inform other organizations interested in implementing PGx testing for mental health. Further, this study demonstrates the application of BWS to PGx, the findings of which may be used by other organizations to inform implementation of PGx testing for mental health disorders.Item Ensuring Access to Albuterol in Schools: From Policy to Implementation. An Official ATS/AANMA/ALA/NASN Policy Statement(American Thoracic Society, 2021) Volerman, Anna; Lowe, Ashley A.; Pappalardo, Andrea A.; Anderson, Charmayne M. C.; Blake, Kathryn V.; Bryant-Stephens, Tyra; Carr, Thomas; Carter, Heather; Cicutto, Lisa; Gerald, Joe K.; Miller, Tina; Moore, Nuala S.; Phan, Hanna; Sadreameli, S. Christy; Tanner, Andrea; Winders, Tonya A.; Gerald, Lynn B.; School of NursingRationale: For children with asthma, access to quick-relief medications is critical to minimizing morbidity and mortality. An innovative and practical approach to ensure access at school is to maintain a supply of stock albuterol that can be used by any student who experiences respiratory distress. To make this possible, state laws allowing for stock albuterol are needed to improve medication access. Objectives: To provide policy recommendations and outline steps for passing and implementing stock albuterol laws. Methods: We assembled a diverse stakeholder group and reviewed guidelines, literature, statutes, regulations, and implementation documents related to school-based medication access. Stakeholders were divided into two groups—legislation and implementation—on the basis of expertise. Each group met virtually to review documents and draft recommendations. Recommendations were compiled and revised in iterative remote meetings with all stakeholders. Main Results: We offer several recommendations for crafting state legislation and facilitating program implementation. 1) Create a coalition of stakeholders to champion legislation and implement stock albuterol programs. The coalition should include school administrators, school nurses and health personnel, parents, or caregivers of children with asthma, pediatric primary care and subspecialty providers (e.g., pulmonologists/allergists), pharmacists, health department staff, and local/regional/national advocacy organizations. 2) Legislative components critical for effective implementation of stock albuterol programs include specifying that medication can be administered in good faith to any child in respiratory distress, establishing training requirements for school staff, providing immunity from civil liability for staff and prescribers, ensuring pharmacy laws allow prescriptions to be dispensed to schools, and suggesting inhalers with valved holding chambers/spacers for administration. 3) Select an experienced and committed legislator to sponsor legislation and guide revisions as needed during passage and implementation. This person should be from the majority party and serve on the legislature’s health or education committee. 4) Develop plans to disseminate legislation and regulations/policies to affected groups, including school administrators, school nurses, pharmacists, emergency responders, and primary/subspecialty clinicians. Periodically evaluate implementation effectiveness and need for adjustments. Conclusions: Stock albuterol in schools is a safe, practical, and potentially life-saving option for children with asthma, whether asthma is diagnosed or undiagnosed, who lack access to their personal quick-relief medication. Legislation is imperative for aiding in the adoption and implementation of school stock albuterol policies, and key policy inclusions can lay the groundwork for success. Future work should focus on passing legislation in all states, implementing policy in schools, and evaluating the impact of such programs on academic and health outcomes.Item Geography, generalisability, and susceptibility in clinical trials(Elsevier, 2021) Clougherty, Jane E.; Kinnee, Ellen J.; Cardet, Juan Carlos; Mauger, David; Bacharier, Leonard; Beigelman, Avraham; Blake, Kathryn V.; Cabana, Michael D.; Castro, Mario; Chmiel, James F.; Covar, Ronina; Fitzpatrick, Anne; Gaffin, Jonathan M.; Gentile, Deborah; Israel, Elliot; Jackson, Daniel J.; Kraft, Monica; Krishnan, Jerry A.; Kumar, Harsha Vardhan; Lang, Jason E.; Lazarus, Stephen C.; Lemanske, Robert F.; Lima, John; Martinez, Fernando D.; Morgan, Wayne; Moy, James; Myers, Ross; Naureckas, Edward T.; Ortega, Victor E.; Peters, Stephen P.; Phipatanakul, Wanda; Pongracic, Jacqueline A; Ross, Kristie; Sheehan, William J.; Smith, Lewis J.; Solway, Julian; Sorkness, Christine A.; Wechsler, Michael E.; Wenzel, Sally; White, Steven R.; Holguin, Fernando; Pediatrics, School of MedicineItem Implementing a pragmatic clinical trial to tailor opioids for acute pain on behalf of the IGNITE ADOPT PGx investigators.(Wiley, 2022-07-28) Cavallari, Larisa H.; Cicali, Emily; Wiisanen, Kristin; Fillingim, Roger B.; Chakraborty, Hrishikesh; Myers, Rachel A.; Blake, Kathryn V.; Asiyanbola, Bolanle; Baye, Jordan F.; Bronson, Wesley H.; Cook, Kelsey J.; Elwood, Erica N.; Gray, Chancellor F.; Gong, Yan; Hines, Lindsay; Kannry, Joseph; Kucher, Natalie; Lynch, Sheryl; Nguyen, Khoa A.; Obeng, Aniwaa Owusu; Pratt, Victoria M.; Prieto, Hernan A.; Ramos, Michelle; Sadeghpour, Azita; Singh, Rajbir; Rosenman, Marc; Starostik, Petr; Thomas, Cameron D.; Tillman, Emma; Dexter, Paul R.; Horowitz, Carol R.; Orlando, Lori A.; Peterson, Josh F.; Skaar, Todd C.; Van Driest, Sara L.; Volpi, Simona; Voora, Deepak; Parvataneni, Hari K.; Johnson, Julie A.Opioid prescribing for postoperative pain management is challenging because of inter-patient variability in opioid response and concern about opioid addiction. Tramadol, hydrocodone, and codeine depend on the cytochrome P450 2D6 (CYP2D6) enzyme for formation of highly potent metabolites. Individuals with reduced or absent CYP2D6 activity (i.e., intermediate metabolizers [IMs] or poor metabolizers [PMs], respectively) have lower concentrations of potent opioid metabolites and potentially inadequate pain control. The primary objective of this prospective, multicenter, randomized pragmatic trial is to determine the effect of postoperative CYP2D6-guided opioid prescribing on pain control and opioid usage. Up to 2020 participants, age ≥8 years, scheduled to undergo a surgical procedure will be enrolled and randomized to immediate pharmacogenetic testing with clinical decision support (CDS) for CYP2D6 phenotype-guided postoperative pain management (intervention arm) or delayed testing without CDS (control arm). CDS is provided through medical record alerts and/or a pharmacist consult note. For IMs and PM in the intervention arm, CDS includes recommendations to avoid hydrocodone, tramadol, and codeine. Patient-reported pain-related outcomes are collected 10 days and 1, 3, and 6 months after surgery. The primary outcome, a composite of pain intensity and opioid usage at 10 days postsurgery, will be compared in the subgroup of IMs and PMs in the intervention (n = 152) versus the control (n = 152) arm. Secondary end points include prescription pain medication misuse scores and opioid persistence at 6 months. This trial will provide data on the clinical utility of CYP2D6 phenotype-guided opioid selection for improving postoperative pain control and reducing opioid-related risks.Item Multisite evaluation of institutional processes and implementation determinants for pharmacogenetic testing to guide antidepressant therapy.(Wiley, 2022-02) Tuteja, Sony; Salloum, Ramzi G.; Elchynski, Amanda L.; Smith, D. Max; Rowe, Elizabeth; Blake, Kathryn V.; Limdi, Nita A.; Aquilante, Christina L.; Bates, Jill; Beitelshees, Amber L.; Cipriani, Amber; Duong, Benjamin Q.; Empey, Philip E.; Formea, Christine M.; Hicks, J. Kevin; Mroz, Pawel; Oslin, David; Pasternak, Amy L.; Petry, Natasha; Ramsey, Allyson; Swain, Sandra M.; Ward, Kristen M.; Wiisanen, Kristin; Skaar, Todd C.; Van Driest, Sara L.; Cavallari, Larisa H.; Bishop, Jeffrey R.There is growing interest in utilizing pharmacogenetic (PGx) testing to guide antidepressant use, but there is lack of clarity on how to implement testing into clinical practice. We administered two surveys at 17 sites that had implemented or were in the process of implementing PGx testing for antidepressants. Survey 1 collected data on the process and logistics of testing. Survey 2 asked sites to rank the importance of Consolidated Framework for Implementation Research (CFIR) constructs using best-worst scaling choice experiments. Of the 17 sites, 13 had implemented testing and four were in the planning stage. Thirteen offered testing in the outpatient setting, and nine in both outpatient/inpatient settings. PGx tests were mainly ordered by psychiatry (92%) and primary care (69%) providers. CYP2C19 and CYP2D6 were the most commonly tested genes. The justification for antidepressants selected for PGx guidance was based on Clinical Pharmacogenetics Implementation Consortium guidelines (94%) and US Food and Drug Administration (FDA; 75.6%) guidance. Both institutional (53%) and commercial laboratories (53%) were used for testing. Sites varied on the methods for returning results to providers and patients. Sites were consistent in ranking CFIR constructs and identified patient needs/resources, leadership engagement, intervention knowledge/beliefs, evidence strength and quality, and the identification of champions as most important for implementation. Sites deployed similar implementation strategies and measured similar outcomes. The process of implementing PGx testing to guide antidepressant therapy varied across sites, but key drivers for successful implementation were similar and may help guide other institutions interested in providing PGx-guided pharmacotherapy for antidepressant management.Item Opportunity for Genotype-Guided Prescribing Among Adult Patients in 11 US Health Systems.(Wiley, 2021-07) Hicks, J. Kevin; El Rouby, Nihal; Ong, Henry H.; Schildcrout, Jonathan S.; Ramsey, Laura B.; Shi, Yaping; Anne Tang, Leigh; Aquilante, Christina L.; Beitelshees, Amber L.; Blake, Kathryn V.; Cimino, James J.; Davis, Brittney H.; Empey, Philip E.; Kao, David P.; Lemkin, Daniel L.; Limdi, Nita A.; P Lipori, Gloria; Rosenman, Marc B.; Skaar, Todd C.; Teal, Evgenia; Tuteja, Sony; Wiley, Laura K.; Williams, Helen; Winterstein, Almut G.; Van Driest, Sara L.; Cavallari, Larisa H.; Peterson, Josh F.The value of utilizing a multigene pharmacogenetic panel to tailor pharmacotherapy is contingent on the prevalence of prescribed medications with an actionable pharmacogenetic association. The Clinical Pharmacogenetics Implementation Consortium (CPIC) has categorized over 35 gene-drug pairs as "level A," for which there is sufficiently strong evidence to recommend that genetic information be used to guide drug prescribing. The opportunity to use genetic information to tailor pharmacotherapy among adult patients was determined by elucidating the exposure to CPIC level A drugs among 11 Implementing Genomics In Practice Network (IGNITE)-affiliated health systems across the US. Inpatient and/or outpatient electronic-prescribing data were collected between January 1, 2011 and December 31, 2016 for patients ≥ 18 years of age who had at least one medical encounter that was eligible for drug prescribing in a calendar year. A median of ~ 7.2 million adult patients was available for assessment of drug prescribing per year. From 2011 to 2016, the annual estimated prevalence of exposure to at least one CPIC level A drug prescribed to unique patients ranged between 15,719 (95% confidence interval (CI): 15,658-15,781) in 2011 to 17,335 (CI: 17,283-17,386) in 2016 per 100,000 patients. The estimated annual exposure to at least 2 drugs was above 7,200 per 100,000 patients in most years of the study, reaching an apex of 7,660 (CI: 7,632-7,687) per 100,000 patients in 2014. An estimated 4,748 per 100,000 prescribing events were potentially eligible for a genotype-guided intervention. Results from this study show that a significant portion of adults treated at medical institutions across the United States is exposed to medications for which genetic information, if available, should be used to guide prescribing.Item Prescribing Prevalence of Medications With Potential Genotype-Guided Dosing in Pediatric Patients(American Medical Association, 2020-12) Ramsey, Laura B.; Ong, Henry H.; Schildcrout, Jonathan S.; Shi, Yaping; Tang, Leigh Anne; Hicks, J. Kevin; El Rouby, Nihal; Cavallari, Larisa H.; Tuteja, Sony; Aquilante, Christina L.; Beitelshees, Amber L.; Lemkin, Daniel L.; Blake, Kathryn V.; Williams, Helen; Cimino, James J.; Davis, Brittney H.; Limdi, Nita A.; Empey, Philip E.; Horvat, Christopher M.; Kao, David P.; Lipori, Gloria P.; Rosenman, Marc B.; Skaar, Todd C.; Teal, Evgenia; Winterstein, Almut G.; Obeng, Aniwaa Owusu; Salyakina, Daria; Gupta, Apeksha; Gruber, Joshua; McCafferty-Fernandez, Jennifer; Bishop, Jeffrey R.; Rivers, Zach; Benner, Ashley; Tamraz, Bani; Long-Boyle, Janel; Peterson, Josh F.; Van Driest, Sara L.; Pediatrics, School of MedicineImportance: Genotype-guided prescribing in pediatrics could prevent adverse drug reactions and improve therapeutic response. Clinical pharmacogenetic implementation guidelines are available for many medications commonly prescribed to children. Frequencies of medication prescription and actionable genotypes (genotypes where a prescribing change may be indicated) inform the potential value of pharmacogenetic implementation. Objective: To assess potential opportunities for genotype-guided prescribing in pediatric populations among multiple health systems by examining the prevalence of prescriptions for each drug with the highest level of evidence (Clinical Pharmacogenetics Implementation Consortium level A) and estimating the prevalence of potential actionable prescribing decisions. Design, setting, and participants: This serial cross-sectional study of prescribing prevalences in 16 health systems included electronic health records data from pediatric inpatient and outpatient encounters from January 1, 2011, to December 31, 2017. The health systems included academic medical centers with free-standing children's hospitals and community hospitals that were part of an adult health care system. Participants included approximately 2.9 million patients younger than 21 years observed per year. Data were analyzed from June 5, 2018, to April 14, 2020. Exposures: Prescription of 38 level A medications based on electronic health records. Main outcomes and measures: Annual prevalence of level A medication prescribing and estimated actionable exposures, calculated by combining estimated site-year prevalences across sites with each site weighted equally. Results: Data from approximately 2.9 million pediatric patients (median age, 8 [interquartile range, 2-16] years; 50.7% female, 62.3% White) were analyzed for a typical calendar year. The annual prescribing prevalence of at least 1 level A drug ranged from 7987 to 10 629 per 100 000 patients with increasing trends from 2011 to 2014. The most prescribed level A drug was the antiemetic ondansetron (annual prevalence of exposure, 8107 [95% CI, 8077-8137] per 100 000 children). Among commonly prescribed opioids, annual prevalence per 100 000 patients was 295 (95% CI, 273-317) for tramadol, 571 (95% CI, 557-586) for codeine, and 2116 (95% CI, 2097-2135) for oxycodone. The antidepressants citalopram, escitalopram, and amitriptyline were also commonly prescribed (annual prevalence, approximately 250 per 100 000 patients for each). Estimated prevalences of actionable exposures were highest for oxycodone and ondansetron (>300 per 100 000 patients annually). CYP2D6 and CYP2C19 substrates were more frequently prescribed than medications influenced by other genes. Conclusions and relevance: These findings suggest that opportunities for pharmacogenetic implementation among pediatric patients in the US are abundant. As expected, the greatest opportunity exists with implementing CYP2D6 and CYP2C19 pharmacogenetic guidance for commonly prescribed antiemetics, analgesics, and antidepressants.Item Rationale and design for a pragmatic randomized trial to assess gene-based prescribing for SSRIs in the treatment of depression(Wiley, 2024) Hines, Lindsay J.; Wilke, Russell A.; Myers, Rachel; Mathews, Carol A.; Liu, Michelle; Baye, Jordan F.; Petry, Natasha; Cicali, Emily J.; Duong, Benjamin Q.; Elwood, Erica; Hulvershorn, Leslie; Nguyen, Khoa; Ramos, Michelle; Sadeghpour, Azita; Wu, R. Ryanne; Williamson, Lloyda; Wiisanen, Kristin; Voora, Deepak; Singh, Rajbir; Blake, Kathryn V.; Murrough, James W.; Volpi, Simona; Ginsburg, Geoffrey S.; Horowitz, Carol R.; Orlando, Lori; Chakraborty, Hrishikesh; Dexter, Paul; Johnson, Julie A.; Skaar, Todd C.; Cavallari, Larisa H.; Van Driest, Sara L.; Peterson, Josh F.; IGNITE Pragmatic Trials Network; Psychiatry, School of MedicineSpecific selective serotonin reuptake inhibitors (SSRIs) metabolism is strongly influenced by two pharmacogenes, CYP2D6 and CYP2C19. However, the effectiveness of prospectively using pharmacogenetic variants to select or dose SSRIs for depression is uncertain in routine clinical practice. The objective of this prospective, multicenter, pragmatic randomized controlled trial is to determine the effectiveness of genotype-guided selection and dosing of antidepressants on control of depression in participants who are 8 years or older with ≥3 months of depressive symptoms who require new or revised therapy. Those randomized to the intervention arm undergo pharmacogenetic testing at baseline and receive a pharmacy consult and/or automated clinical decision support intervention based on an actionable phenotype, while those randomized to the control arm have pharmacogenetic testing at the end of 6-months. In both groups, depression and drug tolerability outcomes are assessed at baseline, 1 month, 3 months (primary), and 6 months. The primary end point is defined by change in Patient-Reported Outcomes Measurement Information System (PROMIS) Depression score assessed at 3 months versus baseline. Secondary end points include change inpatient health questionnaire (PHQ-8) measure of depression severity, remission rates defined by PROMIS score < 16, medication adherence, and medication side effects. The primary analysis will compare the PROMIS score difference between trial arms among those with an actionable CYP2D6 or CYP2C19 genetic result or a CYP2D6 drug-drug interaction. The trial has completed accrual of 1461 participants, of which 562 were found to have an actionable phenotype to date, and follow-up will be complete in April of 2024.