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

1. The FDA accelerated approval process might get your pharmacist-spidey senses going, but is it a concern?

2. 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

3. 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.

4. Is there promise for patients with NAFLD to take their livers back in time? --> Tune in to find out!

References

1. [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.
2. 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.
3. 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.
4. 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: [email protected]

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

1. 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.
2. 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.
3. 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.
4. Is phenobarbital back again for alcohol withdrawal syndrome? --> Tune in to find out!

References

1. [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
2. DiCenzo R. Clinical Pharmacist's Guide to Biostatistics and Literature Evaluation. ACCP. 2011. [Poisson and Wilcoxan information]
3. The ASAM Clinical Practice Guideline on Alcohol Withdrawal Management. American Society of Addiction Medicine, 2020. [Alcohol withdrawal management information, CIWA, PAWSS]
4. Weaver M, Jewell C, Tomlinson J. Phenobarbital for Treatment of Alcohol Withdrawal. Journal of Addictions Nursing 2009;20:1-5.

Contact Information

Podcast email: [email protected]

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

1. Biologic agents are key in managing or preventing certain disease states, however often they present cost challenges to patients and healthcare systems
2. Febrile Neutropenia (FN) is a complication of high intensity chemotherapy regimens for patients with cancer
3. 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
4. Equivalence studies present an opportunity for pharmacists to critically evaluate historical data to determine clinical and statistical appropriateness of equivalence margins
5. How can you best interpret equivalence margins? ---> Tune in to find out!

References

1. [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.
2. 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.
3. Casazza G, Solbiati M.  Can we trust equivalence and non-inferiority trials? Intern Emerg Med 2013;8:439-442.
4. 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: [email protected]

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

1. C. Difficile infections are a public health concern and put a heavy burden on the health care system
2. 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
3. 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
4. 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: 

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

1. Migraine disease affects 1 in 6 Americans and is a leading cause of disability
2. Triptan medications have been used for decades to treat migraine attacks, yet they have several contraindications due to vasoconstrictive effects
3. CGRP inhibitors are a new class of medications that target a specific peptide involved in migraine disease pathophysiology
4. 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
5. Does migraine disease fit the co-primary mold and is zavegepant ready for the migraine toolbox? --> Tune in to find out!

References

1. [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.  
2.  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.
3.  Product Information: Zavzpret(R), zavegepant 10mg/1 nasal spray. Pfizer Laboratories Div Pfizer Inc, New York, NY. 2023.
4. 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.
5. 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: [email protected]

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

1. Non-inferiority (NI) trials are indicated when there are other effective treatment options or where it would unethical to expose a group to placebo
2. Acinetobacter baumannii-calcoaceticus (ABC) is seen in hospital acquired infections and presents a clinical challenge to practitioners given its increasing resistance patterns
3. NI margins are important components to critique when reviewing these trials to determine clinical implications and whether the margin is clinically justifiable 
4. How inferior is considered "non-inferior"? --> Tune in to find out!

References

1. [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.
2. 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
3.  Product Information: XACDURO(R) intravenous kit, sulbactam, durlobactam intravenous kit. La Jolla Pharmaceutical Company (per manufacturer), Waltham, MA, 2023.
4. 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: [email protected]

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

Welcome to What’s it Worth! Join your host, Dr. Diana Langworthy and co-host Chelsea Bolier, PharmD, as we break down Delphi and learn more about analyzing qualitatitve data.  We're joined this month by Dr. Joel Farley, PhD and Dr. Pamela Phelps, PharmD, FASHP - two experts in the arena of determining the impact of clinical pharmacy services. 

Key Points

1. Determining the impact of clinical pharmacist interventions is a complex and site specific process
2. The Delphi (or modified Delphi) process is intended for use to answer a qualitative research question through consensus building among experts
3. Aligning health system patient care priorities with pharmacist clinical impact is key in gaining buy-in for all stakeholders
4. How did Delphi shake out for pharmacist clinical impact? --> Tune in to find out!

References

1. [EPISODE TRIAL] Vest MN, Stout S, Waldron K. Implementation of a strategy for identification and monitoring of clinical outcome measures in a department of pharmacy. Am J Health Syst Pharm 2022;79:e135-142.
2. Nasa P, Jain R, Juneja D. Delphi methodology in healthcare research: How to decide its appropriateness. World Journal of Methodology 2021;11(4):116-129.

Contact Information

Podcast email: [email protected]

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

Guest Host Information

Chelsea Bolier, PharmD, HSPAL PGY1 Pharmacy Resident, M Health Fairview

Joel Farley, PhD, Professor and Associate Department Head, Department of Pharmaceutical Care & Health Systems, Univeristy of Minnesota College of Pharmacy

Pamela Phelps, PharmD, FASHP, Director of Clinical Pharmacy at M Health Fairview

Welcome to What’s it Worth! Join your hosts, Dr. Diana Langworthy & Garrison Griest as we go retro to tackle confounding variables! We'll be reviewing an article that aimed to determine the risk of spontaneous bacterial peritonitis (SBP) in patients with cirrhosis who are using proton pump inhibitors (PPIs).

Key Points

1. Retrospective studies produce more opportunities for confounding variables to impact study results
2. Proton pump inhibitors are widely used and overused for acid reflux disease and have been associated with several risks
3. Odds ratios calculated for retrospective cohort studies determine associations between an intervention and a risk
4. How much confouding is too much? --> Tune in to find out!

References

1. [EPISODE TRIAL] Dahabra L, Kreidieh M, Abureesh M, et al.  Proton pump inhibitor use and increased risk of spontaneous bacterial peritonitis in chrrhotic patients: A retrospective cohort analysis.  Gastroenterol Res. 2022;15(4):180-187.
2. Biggins SW, Angeli P, Garcia-Tsao G, et al.  Diagnosis, evaluation and management of ascites, spontaneous bacterial peritonitis and hepatorenal syndrome: 2021 practice guidance by the American Association for the Study of Liver Diseases. Hepatology.2021;74(2)1014-1048

Contact Information

Podcast email: [email protected]

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

Guest Host Information

Garrison Griest, Student Pharmacist, Class of 2025  University of Minnesota

08Welcome to What’s it Worth! Join your hosts, Dr. Diana Langworthy, Nathan Uk, and Garrison Griest as we walk you through composite outcomes with the CLEAR trial - a comparison of bempedoic acid versus placebo for preventing major adverse cardiovascular events (MACE) in patients who cannot tolerate statin therapy. We're joined by Dr. Chrystian Pereira, PharmD, BCACP, an ambulatory care pharmacist at the Smiley's Family Medicine Clinic in South Minneapolis, MN. 

Key Points

1. Statins play a key role in prevention of major cardiovascular events (MACE), yet not all patients tolerate them
2. Bempedoic acid may have a place in therapy to prevent MACE for patients who cannot tolerate statins
3. Composite outcomes involve > 1 outcome and they should be of similar clinical severity
4. Learning your POEMs and DOEs of a trial help you critique evidence that matters --> Tune in to learn more about what POEMs and DOEs are!

References

1. [EPISODE TRIAL] Nissen SE, Lincoff AM, Brennan D, et al.  Bempedoic Acid and Cardiovascular Outcomes in Statin-Intolerant Patients. NEJM 2023; DOI: 10.1056/NEJMoa2215024.
2. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines. Circulation 2019;139(25):e1082-e1143.
3. Bytyci I, Penson PE, Mikhailidis DP, et al.  Prevalence of statin intolerance: a meta-analysis.  Eur Heart J 2022;43:3213-23.
4. Shaikh A, Ochani RK, Khan MS, et al.  Contribution of individual components to composite end points in contemporary cardiovascular randomized controlled trials. Am Heart J 2020;230:71-81.

Contact Information

Podcast email: [email protected]

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

Guest Host Information

Garrison Griest, Student Pharmacist, Class of 2025  University of Minnesota

Nathan Uk, Student Pharmacist, Class of 2025  University of Minnesota

Guest Expert

Dr. Chrystian Pereira, PharmD, BCACP, Associate Professor, University of Minnesota College of Pharmacy

Welcome to What’s it Worth! Join your hosts, Dr. Diana Langworthy, Nathan Uk, and Garrison Griest as we take on the evidence behind a trending treatment for COVID-19.  Our guest, Dr. Ann Philbrick, PharmD, BCACP, will share her expertise with medical cannabis products to help figure out what is TBD about CBD in COVID-19.  

Key Points

1. Cannabidiol (CBD) has some purported anti-inflammatory properties from in-vitro studies and was investigated to prevent progression of COVID-19 to moderate or severe disease
2. Pharmacists can use their EBP skills to serve as information experts to prevent progression of information to misinformation!
3. Recognizing statistical tests (i.e. Student's T Test and Chi Square Test) and the data they are used to analyze is a core skills of evidence analysis
4. Cannabidiol doses used in this investigation were much higher than typical CBD doses in OTC products
5. Peanutbutter has evidence for use in a scientific smell test -> TUNE IN to find out more about the science behind the peanutbutter smell test!

References

1. [EPISODE TRIAL] Crippa JAS, Pacheco JC, Zuardi AW, et al.  Cannabidiol for COVID-19 Patients with Mild to Moderate Symptoms (CANDIDATE Study): A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.  Cannabis and Cannabinoid Research 2022;7(5):658-669.
2. Stamps JJ, Bartoshuk LM, Heilman KM.  A brief olfactory test for Alzheimer's disease.  Journal of the Neurological Sciences 2013;333(1-2):19-24. [NOTE: this peanutbutter smell test results have not been successfully replicated in other studies so it's true utility is not clear]
3. DiCenzo, Robert. “Choosing the Appropriate Statistical Test.” Clinical Pharmacist’s Guide to Biostatistics and Literature Evaluation, American College of Clinical Pharmacy, Lenexa, KS, 2015, pp. 23–37.  

Contact Information

Podcast email: [email protected]

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

Guest Host Information

Garrison Griest, Student Pharmacist, Class of 2025  University of Minnesota

Nathan Uk, Student Pharmacist, Class of 2025  University of Minnesota

Guest Expert

Dr. Ann Philbrick, PharmD, BCACP, Associate Professor, University of Minnesota College of Pharmacy