What's it Worth? A Journal Club Podcast Diana Langworthy

Welcome back to What’s it Worth! Join your hosts, Dr. Diana Langworthy and Garrison Avery, student PharmD, as we evaluate the 52 week reported outcomes of the ongoing Resmetirom Phase 3 trial. This trial is our first look at a medication currently seeking FDA approval to halt and reverse NASH and liver fibrosis. We also discuss Bonferroni statistical analysis, patients excluded from the trial, and bias in language. 
 
Key Points
The FDA accelerated approval process might get your pharmacist-spidey senses going, but is it a concern?
Non-alcoholic steatohepatitis (NASH) is the most severe form of non-alcoholic fatty liver disease (NAFLD) and can progress to end stage liver disease if not managed properly
Recognizing when manuscript language may be suggestive of an effect (when one has not been statistically proven) is important to keep top of mind when critiquing an article.
Is there promise for patients with NAFLD to take their livers back in time? --> Tune in to find out! References
[EPISODE TRIAL] Harrison SA, Bedossa P, Guy CD, et al; MAESTRO-NASH Investigators. A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis. N Engl J Med. 2024 Feb 8;390(6):497-509. doi: 10.1056/NEJMoa2309000. PMID: 38324483. Kanwal F, Neuschwander-Tetri BA, Loomba R, Rinella ME.  Metabolic dysfunction-associated steatotic liver disease: Update and impact of new nomenclature on the American Association for the Study of Liver Diseases practice fuidance on nonalcoholic fatty liver disease. Hepatology 2023;DOI: 10.1097/HEP.0000000000000670. Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, et al.  AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease Hepatology 2023;77(5):1797-1835. U.S. Food and Drug Administration. Accelerated Approval Program. Accessed March 8, 2024. https://www.fda.gov/drugs/nda-and-bla-approvals/accelerated-approval-program Contact Information
Podcast email: whatsitworthpodcast@gmail.com
Host Information
Dr. Diana R. Langworthy, PharmD, BCPS
Clinical Associate Professor, University of Minnesota College of Pharmacy
Clinical Pharmacist - Inpatient Internal Medicine, M Health Fairview East Bank Hospital
Co-Host Information
Garrison (Griest) Avery, Student Pharmacist, Class of 2024
University of Minnesota College of Pharmacy

Did you miss us? We're back for Season 2 of What’s it Worth! Join your host, Dr. Diana Langworthy, and co-host Garrison (Griest) Avery (back at the end of his APPE year for some more EBP fun!), as they find out if phenobarbital is beating benzos in severe alcohol withdrawal!  CI-WAt all the fuss is about in season two as we PAWSS and reflect on where single-site retrospective results and clinical takeaways can meet!
 
Key Points
Alcohol withdrawal syndrome is a complex process involving acute imbalances in excitatory and inhibitory neurotransmitters in the CNS that can predispose patients to potentially life threatening complications like seizure and alcohol withdrawal delirium. Patients in vulnerable populations, like pregnant persons and imprisoned persons, represent a group that is often underrepresented in clinical trials - we discuss this from a retrospective and prospective angle. The Poisson regression is used for analysis of count data while the Wilcoxan rank sum test is a nonparametric test that assumes unknown or not-normally distrubuted data. Is phenobarbital back again for alcohol withdrawal syndrome? --> Tune in to find out! References
[EPISODE TRIAL] D, Al-Hegelan M, Thompson J, Bronshteyn Y. Phenobarbital versus benzodiazepines in alcohol withdrawal syndrome. Neuropsychopharmacol Rep. 2023; 43: 532–541. https://doi.org/10.1002/npr2.12347 DiCenzo R. Clinical Pharmacist's Guide to Biostatistics and Literature Evaluation. ACCP. 2011. [Poisson and Wilcoxan information] The ASAM Clinical Practice Guideline on Alcohol Withdrawal Management. American Society of Addiction Medicine, 2020. [Alcohol withdrawal management information, CIWA, PAWSS] Weaver M, Jewell C, Tomlinson J. Phenobarbital for Treatment of Alcohol Withdrawal. Journal of Addictions Nursing 2009;20:1-5. Contact Information
Podcast email: whatsitworthpodcast@gmail.com
Host Information
Dr. Diana R. Langworthy, PharmD, BCPS
Clinical Associate Professor, University of Minnesota College of Pharmacy
Clinical Pharmacist - Inpatient Internal Medicine, M Health Fairview East Bank Hospital
Co-Host Information
Garrison (Griest) Avery, Student Pharmacist, Class of 2024
University of Minnesota College of Pharmacy

Welcome to What’s it Worth - BONUS episode #2! Join your host Dr. Diana Langworthy and a come-back by P4 student co-host Marina Fahim as we get biosimilar! Our expert guest for this episode is Dr. Hannah Berg, Formulary Management Pharmacist at United Healthcare. We're discussing a trial that aimed to determine whether pegfilgrastim biosimilars were considered statistically equivalent to the pegfilgrastim originator product.  Biosimilars have the potential to offer cost-savings for patients requiring these expensive agents as they can introduce market competition and a potentially cheaper alternative to originator products.  
This bonus episode also coincides with a Journal Club assignment that students in my Evidence Based Practice course completed last week - Hello PHAR6782 Students! Great work on your first official Journal Clubs!
Key Points
Biologic agents are key in managing or preventing certain disease states, however often they present cost challenges to patients and healthcare systems Febrile Neutropenia (FN) is a complication of high intensity chemotherapy regimens for patients with cancer The NCCN guidelines recommend that patients at high risk receive a granulocyte colony stimulating factor (G-CSF) such as pegfilgrastim for the prevention of FN Equivalence studies present an opportunity for pharmacists to critically evaluate historical data to determine clinical and statistical appropriateness of equivalence margins How can you best interpret equivalence margins? ---> Tune in to find out! References
[EPISODE TRIAL] Wang CY, Vouri SM, Park H, et al.  Comparative effectiveness of pegfilgrastim biosimilars vs originator for prevention of febrile neutropenia: A retrospective cohort study.  J Manag Care Spec Pharm. 2023;29(2):119-127. Griffiths EA, Roy V, Bachiashvili K, et al.  Hematopoietic Growth Factors. NCCN Guidelines Version 1.2024. Accessed at https://www.nccn.org/professionals/physician_gls/pdf/growthfactors.pdf. Casazza G, Solbiati M.  Can we trust equivalence and non-inferiority trials? Intern Emerg Med 2013;8:439-442. Biosimilar Regulatory Review and Approval. US Food and Drug Administration Guidance Document. Accessed at https://www.fda.gov/media/151061/download. Contact Information
Podcast email: whatsitworthpodcast@gmail.com
Host Information
Dr. Diana R. Langworthy, PharmD, BCPS
Clinical Associate Professor, University of Minnesota College of Pharmacy
Clinical Pharmacist - Inpatient Internal Medicine, M Health Fairview East Bank Hospital
Co-Host: Marina Fahim, P4 PharmD Student 2024, University of Minnesota
Expert Guest Information
Dr. Hannah Berg, PharmD
Formulary Management Pharmacist
UnitedHealthcare 

Welcome to What’s it Worth - a BONUS episode! Join your host Dr. Diana Langworthy and a come-back by P4 student co-host Garrison Griest as we get the scoop on poop! Our expert guest for this episode is Dr. Jen Ross, Antimicrobial Stewardship Clinical Pharmacist at M Health Fairview East and West Bank Hospitals. We're discussing a trial that evaluated the efficacy of a new orally administered fecal microbiota transplant capsule - SER-109. 
This episode coincides with a Journal Club assignment that students in my Evidence Based Practice course completed last week - Hello PHAR6782 Students! Great work on your first official Journal Clubs!
Key Points
C. Difficile infections are a public health concern and put a heavy burden on the health care system Patients experiencing recurrent infections often are subject to expensive and/or prolonged antibiotic regimens with an option for site specific fecal microbiota transplant (FMT) at the discretion of their gastroenterologist SER-109 (VOWST) is an orally administered FMT that is intended to be standardized for commercial development that demonstrated a reduction in recurrent C. Diff rates and early re-engraftment of a healthy microbiome What populations are best to analyze for efficacy and safety in this Phase III RCT? ---> Tune in to find out! Erratum: Garrison mention's that patients on prednisone 20mg/day or more were excluded - this was an exclusion criteria for the Rebyota(R) trial and NOT the SER-109 VOWST trial.
As it related to immunosuppressed patients, the SER-109 (VOWST) trial excluded: 
1) Absolute neutrophil count of
2) History of immunoglobulin (IgG) replacement therapy within the past 3 months
3) Concurrent intensive induction chemotherapy, radiotherapy, or biologic treatment for active malignancy (subjects on maintenance chemotherapy may only be enrolled after consultation with the study medical monitor)
References
[EPISODE TRIAL] Feuerstadt P, Louie TJ, Lashner B, et al.  SER-109, an oral microbiome therapy for recurrent Clostridioides difficile infection. NEJM 2022;386:220-229. Johnson S, Lavergne V, Skinner AM, et al.  Clinical practice guideline by the Infectious Disease Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 Focused update guidelines on management of Clostridioides difficile infection in adults. CID 2021:doi.10.1093/cid/ciab549. Khanna S, Assi M, Lee C, et al. Efficacy and Safety of RBX2660 in PUNCH CD3, a Phase III, Randomized, Double-Blind, Placebo-Controlled Trial with a Bayesian Primary Analysis for the Prevention of Recurrent Clostridioides difficile Infection. Drugs. 2022;82(15):1527-1538.
doi:10.1007/s40265-022-01797-x [Equity check reference] Argamany JR, Delgado A, Reveles KR. Clostridium difficile infection health disparities by race among hospitalized adults in the United States, 2001 to 2010. BMC Infect Dis 2016;16(1): 454. Contact Information
Podcast email: whatsitworthpodcast@gmail.com
Host Information
Dr. Diana R. Langworthy, PharmD, BCPS
Clinical Associate Professor, University of Minnesota College of Pharmacy
Clinical Pharmacist - Inpatient Internal Medicine, M Health Fairview East Bank Hospital
Co-Host: Garrison Griest, P4 PharmD Student 2024, University of Minnesota
Expert Guest Information
Dr. Jennifer Ross, PharmD, BCIDP
Infectious Disease Clinical Pharmacist
East and West Bank Hospitals, M Health Fairview

Welcome to What’s it Worth! Join your host Dr. Diana Langworthy as we co-mingle with co-primary clues! Our expert guest for this episode is Dr. Natalie Heinrich, Medication Therapy Management Clinical Pharmacist in Neurology at M Health Fairview. We're discussing a trial evaluated the efficacy of zavegepant, a novel CGRP antagonist for nasal administration, for the treatment of acute migraine attack. Join us as we discuss the key points of co-primary outcomes, populations and power.
 
Key Points
Migraine disease affects 1 in 6 Americans and is a leading cause of disability Triptan medications have been used for decades to treat migraine attacks, yet they have several contraindications due to vasoconstrictive effects CGRP inhibitors are a new class of medications that target a specific peptide involved in migraine disease pathophysiology Treatment for some disease states requires studies that involve two co-primary outcomes that are deemed equally important to determine true efficacy of an intervention Does migraine disease fit the co-primary mold and is zavegepant ready for the migraine toolbox? --> Tune in to find out! References
[EPISODE TRIAL] Lipton RB, Croop R, Stock DA, et al.  Safety, tolerability, and efficacy of zavegepant 10mg nasal spray for the acute treatment of migraine in the USA: a phase 3, double-blind, randomised, placebo-controlled multicentre trial. Lancet Neurol 2023;22(3):209-217.    Croop R, Madonia J, Stock DA, et al.  Zavegepant nasal spray for the acute treatment of migraine: a phase 2/3 double-blind, randomized, placebo-controlled, dose-ranging trial. Headache 2022;62:1153-1163.  Product Information: Zavzpret(R), zavegepant 10mg/1 nasal spray. Pfizer Laboratories Div Pfizer Inc, New York, NY. 2023. Ailani J, Burch RC, Robbins MS, et al.  The American Headache Society Consensus Statement: Update on integrating new migraine treatments into clinical practice. Headache 2021;61:1021-1039. Burch R, Rizzoli P, Loder E.  The Prevalence and Impact of Migraine and Severe Headache in the United States: Figures and Trends from Government Health Studies. Headache 2018;58(4):496-505. Contact Information
Podcast email: whatsitworthpodcast@gmail.com
Host Information
Dr. Diana R. Langworthy, PharmD, BCPS
Clinical Associate Professor, University of Minnesota College of Pharmacy
Clinical Pharmacist - Inpatient Internal Medicine, M Health Fairview East Bank Hospital
Expert Guest Information
Dr. Natalie Heinrich, PharmD
Medication Therapy Management Clinical Pharmacist, Neurology
Clinics and Surgery Center, M Health Fairview

Welcome to What’s it Worth! Join your host Dr. Diana Langworthy, & co-host Marina Fahim, as we ATTACK the critique of a non-inferiotiy study design. Our expert guest for this episode is Dr. Betsy Hirsch, Assoiate Professor and Infectious Diseases Translational Researcher. We're discussing a trial that compared a new beta-lactam antibiotic, sulbactam/durlobactam, with colistin for the treatment of Acinetobacter baumannii infections. Join us as we discuss the key points of a non-inferiority trial design as we determine what this article is worth!
 
Key Points
Non-inferiority (NI) trials are indicated when there are other effective treatment options or where it would unethical to expose a group to placebo Acinetobacter baumannii-calcoaceticus (ABC) is seen in hospital acquired infections and presents a clinical challenge to practitioners given its increasing resistance patterns NI margins are important components to critique when reviewing these trials to determine clinical implications and whether the margin is clinically justifiable  How inferior is considered "non-inferior"? --> Tune in to find out! References
[EPISODE TRIAL] Kaye KS, Shorr AF, Wunderink RG, et al.  Efficacy and safety of sulbactam-durlobactam versus colistin for the treatment of patients with serious infections caused by Acinetobacter baumannii-calcoaceticus complex:  a multicentre, randomised, active-controlled, phase 3, non-inferiority clinical trial (ATTACK).  Lanced Infect Dis 2023; Sep;23(9):1072-1084.  doi: 10.1016/S1473-3099(23)00184-6. Tamma PD, Aitken SL, Bonomo RA, et al.  Infectious Diseases Society of America 2023 Guidance on the Treatment of Antimicrobial Resistant Gram-Negative Infections. CID 2023, ciad428,  https://doi.org/10.1093/cid/ciad428  Product Information: XACDURO(R) intravenous kit, sulbactam, durlobactam intravenous kit. La Jolla Pharmaceutical Company (per manufacturer), Waltham, MA, 2023. Tsuji BT, Pogue JM, Zavascki AP, et al.  International Consensus Guidelines for the Optimal Use of the Polymyxins: Endorsed by the American College of Clinical Pharmacy (ACCP), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Infectious Diseases Society of America (IDSA), International Society for Anti-Infective Pharmacology (ISAP), Society of Critical Care Medicine (SCCM), and Society of Infectious Diseases Pharmacists (SIDP).  Pharmacotherapy 2019;39(1):10-39.  https://accpjournals.onlinelibrary.wiley.com/doi/full/10.1002/phar.2209 Contact Information
Podcast email: whatsitworthpodcast@gmail.com
Host Information
Dr. Diana R. Langworthy, PharmD, BCPS
Clinical Associate Professor, University of Minnesota College of Pharmacy
Clinical Pharmacist - Inpatient Internal Medicine, M Health Fairview East Bank Hospital
Co-Host Information
Marina Fahim, Student Pharmacist, Class of 2024  University of Minnesota
Guest Host Information
Dr. Betsy Hirsch, PharmD, FCCP, FIDSA
Associate Professor, Experimental and Clinical Pharmacology
Infectious Diseases Translational Researcher
University of Minnesota College of Pharmacy