Asthma, Author Interviews / 03.11.2020 Interview with: Hahn, PhD, Director U.S. Value Evidence and Outcomes, GlaxoSmithKline, Research Triangle Park, NC What is the background for this study? Response: Biologic therapies are increasing as a treatment for patients with severe asthma, with multiple therapies approved by the FDA.  There is also an increasing understanding of the factors influencing preference for and adherence to biologic therapies for patients with severe asthma; however, little is known about why patients discontinue biologic therapy. In patients who have access to biologic treatment, understanding the circumstances and asthma characteristics associated with discontinuation of biologic therapy may allow for the identification of barriers to treatment success . The objective of this study of cross-sectional physician and patient survey data was to assess the patient characteristics and the given reasons for treatment discontinuation in a US patient cohort with severe asthma treated with biologic therapy. A total of 117 physicians and 285 patients completed surveys with 70% of patients continuing biologic therapy (N=200). This study included a number of different FDA approved biologics. From the perspectives of the physicians included in the current study (85 providing a rationale for discontinuation), the majority reported a lack of symptom control, particularly shortness of breath (46%), exacerbations (26%) and other chronic symptoms (29%), as a key reason for discontinuing biologic therapy in severe asthma. Symptom control was also key for patients, with these three symptom categories among their top six reasons for biologic discontinuation. The cost of biologic treatment was also an important factor, cited as the 5th most common reason for discontinuation among physicians and the 3rd among patients. (more…)
Author Interviews / 24.07.2020 Interview with: Brian Shoichet, Professor UCSF What is the background for this study? Response: Excipients are ubiquitous in drug formulations.  What most people consider "drugs" are formulations of active and "inactive" ingredients--the excipients.  These "inactive" ingredients, which you can find on the label of all of the drugs you use, play crucial roles in drug stability, as antioxidants, as colorants to help patients distinguish among them, as anti-microbials to keep them from getting infected with bacteria, helping to make the soluble  in the patient, among other functions. They are considered "inactive" because they do not have observable toxicity in animal and sometimes histological studies, but few of them have been evaluated in a modern way.  This would involve testing the excipients for activity on individual receptors and enzymes that are involved in biological responses, which is what happens for drugs.  Doing this was the focus of this study (more…)
Author Interviews, Cost of Health Care / 10.03.2020 Interview with: Olivier Wouters, Ph.D. Assistant Professor of Health Policy Department of Health Policy London School of Economics and Political Science London What is the background for this study? Response: Although both Democrats and Republicans consider lowering prescription drug prices a priority, lobbyists and campaign donors in the pharmaceutical industry may counteract efforts by federal and state governments to decrease these costs. In this study, I tracked every dollar spent by the pharmaceutical and health product industry on lobbying and campaign contributions in the US from 1999 to 2018. These data were obtained from the Center for Responsive Politics and the National Institute on Money in Politics—two non-profit, non-partisan US organizations.  (more…)
Author Interviews, Cost of Health Care, JAMA, Pharmaceutical Companies / 04.03.2020 Interview with: Olivier Wouters, Ph.D. Assistant Professor of Health Policy Department of Health Policy (COW 2.06) London School of Economics and Political Science What is the background for this study? What are the main findings? Response: Drug companies often point to high research and development costs as justification for the rising prices of new medicines. Yet most prior analyses of research and development costs have been based on confidential data voluntarily supplied by drug companies to researchers with financial ties to the industry. Independent teams have not been able to verify those findings. (more…)
Author Interviews, Cost of Health Care, Emergency Care / 22.02.2020 Interview with: Collin Tebo BA Georgetown University School of Medicine Washington, DCCollin Tebo BA Georgetown University School of Medicine Washington, DC What is the background for this study? Response: The growing cost of pharmaceuticals is an issue of increasing concern in the United States where a large portion of the nation’s Gross Domestic Product is health care spending. During the past decade, visits to Emergency Departments (EDs) have increased considerably. Pharmaceutical drugs are utilized in the care of most patients who visit the ED therefore, rising drug prices are a concern for emergency medicine physicians, administrators, and patients throughout the US. (more…)
ASCO, Author Interviews, Bayer, Cancer Research / 11.02.2020 Interview with: bayer-pharmaceuticalsDr. Kirhan Ozgurdal Global Medical Affairs Physician Oncology, Bayer What is the background for this study? What are the main findings?
  • Regorafenib is an oral multi-kinase inhibitor that potently blocks multiple protein kinases involved in tumor angiogenesis, oncogenesis, metastasis and tumor immunity. It is approved for the treatment of patients with hepatocellular carcinoma (HCC) who have previously been treated with sorafenib. The safety and effectiveness of regorafenib is being evaluated in patients with unresectable hepatocellular carcinoma (uHCC),a liver tumor not eligible for curative treatment approaches such as surgery, given the extent of disease.
  • Following the Phase 3 RESORCE trial, which showed that regorafenib significantly improves overall survival versus placebo in patients with uHCC who progressed on prior sorafenib therapy, we conducted an interim analysis (the first 500 of 1000 patients) of the global REFINE observational trial to evaluate the safety and effectiveness of regorafenib in uHCC in the real-world setting.
  • The REFINE study shows a more varied patient population than the Phase 3 RESORCE trial, including a higher proportion of patients with ECOG performance status ≥1, and a higher proportion with Child–Pugh B liver function.
  • The incidence of regorafenib-related grade ≥3 treatment-emergent adverse events were lower than that reported in the RESORCE trial, possibly indicating improved adverse event management with the use of regorafenib in clinical practice.
  • The median overall survival was longer than that reported in RESORCE, but the proportion of censored patients was high in this interim analysis; the median progression free survival was similar to that reported in RESORCE.
Author Interviews, Dartmouth, JAMA, Pharmaceutical Companies, Primary Care / 27.01.2020 Interview with: Steven Woloshin, MD, MS Professor of Medicine and Community and Family Medicine Professor, The Dartmouth Institute for Health Policy and Clinical Practice What is the background for this study? Response: Industry spends more on detailing visits and free samples than any other form of prescription drug marketing.  There is good evidence that these activities can lead to more use of expensive new drugs over equally effective cheaper options.  Given these concerns there have been efforts by some hospitalls and practices to restrict these forms of marketing. We asked physicians in group practices delivering primary care about how often pharmaceutical reps visit their practice and whether they have a free sample closet.  (more…)
Addiction, Author Interviews, CDC, Emory / 20.03.2019 Interview with: CDR Andrew Geller, MD Medical Officer, Medication Safety Program Division of Healthcare Quality Promotion, CDC Atlanta GA 30329 What is the background for this study? Response: There has been a lot of recent attention on drug overdoses in the United States, particularly fatal overdoses which involve opioids. But the overall frequency with which patients end up in the emergency department (ED) due to nonmedical use of medications across the US is unknown.
  • Nonmedical use refers to a spectrum of circumstances, including intentionally using more medication than is recommended in an attempt to treat a health condition (therapeutic misuse) to using medication to attain euphoria or get “high” (abuse).
With this analysis, we wanted to focus on the acute harms to individual patients from nonmedical use of all medications, in order to help target prevention efforts.
  • Specifically, we used data from a nationally-representative sample of hospital EDs to identify the medications with the highest numbers of emergency visits for harms following nonmedical use of medications and to identify the patient groups with the highest risks. 
Author Interviews, Cost of Health Care, JAMA / 30.10.2018 Interview with: Samir C. Grover MD, MEd, FRCPC Division of Gastroenterology Program Director Division of Gastroenterology Education Program University of Toronto What is the background for this study? What are the main findings? Response: We know that physician-industry interactions are commonplace. Because of this, there has been a movement to make the presence of these relationships more transparent. For clinical practice guidelines, this is especially important as these documents are meant to be objectively created, evidence based, and intended to guide clinical practice. The standard in the US come from the National Academy of Medicine report, "Clinical Practice Guidelines We Can Trust", which suggests that guideline chairs should be free of conflicts of interest, less than half of the guideline committee should have conflicts, and that guideline panel members should declare conflicts transparently. Other studies, however, have shown that some guidelines don't adhere to this advice and have committee members who don't disclose all conflicts. We thought to look at this topic among medications that generate the most revenue, hypothesizing that undeclared conflicts would be especially prevalent in this setting. We found that, among 18 guidelines from 10 high revenue medications written by 160 authors, more than (57%) had a financial conflict of interest, meaning they received payments from pharmaceutical companies that make or market medications recommended in that guideline. About a quarter of authors also received, and didn't disclose payments from one of these companies. Almost all the guidelines did not adhere to National Academy of Medicine standards. (more…)
Author Interviews, Pharmaceutical Companies / 31.05.2018 Interview with: “pills” by Dominique Godbout is licensed under CC BY 2.0George P. Ball PhD Operations and Decision Technologies Department Kelley School of Business, Indiana University Bloomington, IN 47405, What is the background for this study? What are the main findings? Response: We sought to examine how the intense pressure on firms to produce generic drugs more cheaply might influence product quality. We find that the greater proportion of generic drugs a firm manufactures, the more severe product recalls they experience, because of an apparent relaxation of manufacturing quality standards. Additionally, they experience fewer less severe recalls, which may also result from forces of competition. When the opportunity exists to not announce a recall that has high discretion, competition may lead firms to forgo the recall to avoid negative ramifications associated with recalls. (more…)
Author Interviews, Cancer Research, Cost of Health Care, JAMA, Pharmaceutical Companies / 09.04.2018 Interview with: Aaron Mitchell, MD Division of Hematology/Oncology, Department of Medicine, Lineberger Comprehensive Cancer Center The Cecil G. Sheps Center for Health Services Research The University of North Carolina at Chapel Hill What is the background for this study? What are the main findings? Response: Financial relationships between physicians and the pharmaceutical industry are very common. However, we are just beginning to figure out whether these relationships may lead to potentially concerning changes in physician behavior - whether physicians tend to prescribe more of the drugs made by a company that has given them money. We decided to ask whether oncologists who receive money from drugmakers are more likely to use the cancer drugs made by companies that have given them money in the past. In studying two specific groups of cancer drugs, one for kidney cancer and one for chronic myeloid leukemia (CML), we found that oncologists who had received payments such as meals, consulting fees, travel & lodging expenses from the manufacturer of one of these drugs tended to use that drug more. When looking at oncologists who received payments for research, we found increased prescribing among the kidney cancer drugs but not the CML drugs. (more…)
Author Interviews, Pain Research, Pharmacology, PLoS / 17.08.2017 Interview with: Harsha Shanthanna MBBS, MD, MSc Associate Professor, Anesthesiology Chronic Pain Physician St Joseph's Healthcare,McMaster University Hamilton, Canada Diplomate in National Board, Anesthesiology (India) Fellow in Interventional Pain Practice (WIP) European Diplomate in Regional Anesthesia and Pain What is the background for this study? Response: Pregabalin (PG) and gabapentin (GB) are increasingly used for nonspecific Chronic Low Back Pain (CLBP) despite a lack of evidence. There have been concerns expressed over their increased prescribing for various non cancer pain indications in recent years. Their use requires slow titration to therapeutic doses and establishing maintenance on a long-term basis. With prolonged treatment, the potential gain over possible adverse effects and risks could become unclear. We searched Cochrane, MEDLINE and EMBASE databases for randomized control trials reporting the use of gabapentinoids for chronic lower back pain treatment of 3 months or more in adult patients. (more…)
Author Interviews, Cost of Health Care, JAMA, Lipids, University of Pittsburgh / 07.08.2017 Interview with: Inmaculada Hernandez, PharmD, PhD Assistant Professor of Pharmacy and Therapeutics University of Pittsburgh School of Pharmacy Pittsburgh, PA 1526 What is the background for this study? Response: A few months ago, the results of the FOURIER trial were published. This trial was the first one to evaluate the efficacy of PCSK9 inhibitors in the prevention of cardiovascular events, since the approval of these agents was based on trials that evaluated their efficacy in reducing levels of LDL-C. The results of the FOURIER trial did not meet the expectations generated by prior studies that had simulated how much the risk of cardiovascular events should decrease based on the observed reduction in LDL-C levels. A few hours after the publication of the results of the FOURIER trial, Amgen (evolocumab´s manufacturer) announced that it would be willing to engage in contracts where the cost of evolocumab would be refunded for those patients who suffer a heart attack or a stroke while using the drug. (more…)
Author Interviews, BMJ, Gastrointestinal Disease / 09.07.2017 Interview with: Ziyad Al-Aly MD FASN Assistant Professor of Medicine Co-director for Clinical Epidemiology Center Department of Medicine, Washington University School of Medicine Saint Louis, Missouri Associate Chief of Staff for Research and Education Veterans Affairs Saint Louis Health Care System What is the background for this study? What are the main findings? Response: Proton Pump Inhibitors (PPI) are commonly used, and they are associated with adverse events including kidney disease, dementia, fractures, cardiovascular disease, and pneumonia. We asked the question of whether this translates to increased risk of death. We conducted this large cohort study to specifically examine the association between PPI use and risk of death. The results consistently showed an association between use of PPI and increased mortality risk. Moreover, there was a graded relationship between duration of PPI use and risk of death in that longer duration of use was associated with incrementally higher risk of death. (more…)
Author Interviews, ESMO, Pharmacology / 09.10.2016 Interview with: Paolo Bossi MD Medical Oncologist Head and Neck Cancer Department IRCCS Istituto Nazionale dei Tumori Foundation Milan, Italy What is the background for this study? What are the main findings? Response: Precise, clear and unbiased reporting of adverse events (AE) is essential to ensure safety of the new drugs. It is crucial also in engaging patients and physicians in a shared decision making: before starting a new treatment I need to discuss with my pt what are the expected benefits and what the toxicities of a new drugs. However, in parallel to the discovery and development of new drugs, little attention has been paid to modernization of the way of collecting toxicities. This line of reasoning is particularly true for new or "relatively new" drugs, such as immunotherapy (IT) and targeted agents (TT). So, we analysed all the trials that lead to the approval of TT or IT from 2000 – 2015 retrieved by FDA database. (more…)
Author Interviews, Cancer Research, JAMA / 25.08.2016 Interview with: Dr. Aaron Mitchell MD Hematology/Oncology Fellow University North Carolina What is the background for this study? Response: It is well known that many physicians work with the pharmaceutical industry. In some cases, this can create conflicts of interest with physicians' other responsibilities. The Open Payments law, passed as part of the Affordable Care Act, recently made these relationships public, which now allows us to study them more systematically. (more…)
Author Interviews, JAMA, Pediatrics, Pharmacology / 16.08.2016 Interview with: Dr Evie Stergiakouli Lecturer in Genetic Epidemiology and Statistical Genetics MRC Integrative Epidemiology Unit University of Bristol Bristol UK What is the background for this study? What are the main findings? Response: Acetaminophen is considered safe to use during pregnancy. However, research suggests that acetaminophen use in pregnancy is associated with abnormal neurodevelopment. It is possible that this association might be confounded by unmeasured behavioural factors linked to acetaminophen use. We compared acetaminophen use during pregnancy to postnatal acetaminophen use and partner's acetaminophen use. Only acetaminophen use during pregnancy has the potential to cause behavioural problems in the offspring. Any associations with postnatal acetaminophen use and partner's acetaminophen use would be due to confounding. Behavioural problems in the offspring were only associated with acetaminophen use during pregnancy. (more…)
Author Interviews, JAMA, Opiods, Toxin Research / 10.08.2016 Interview with: Ann M. Arens, MD California Poison Control Center San Francisco, CA 94110 What is the background for this study? What are the main findings? Response: Prescription opioid abuse is a significant public health threat that has garnered the attention of health care providers throughout medicine. With efforts to curb the number of prescriptions for opioid pain medications, users may begin to purchase prescription medications from illegal sources. Our study reports a series of patients in the San Francisco Bay Area who were exposed to counterfeit alprazolam (Xanax®) tablets found to contain large amounts of fentanyl, an opioid 100 times more potent than morphine, and in some cases etizolam, a benzodiazepine. The California Poison Control System – San Francisco division identified eight patients with unexpected serious health effects after exposure to the tablets including respiratory depression requiring mechanical ventilation, pulmonary edema, cardiac arrest, and one fatality. Patients reportedly purchased the tablets from drug dealers, and were unaware of their true contents. In one case, a 7 month-old infant accidentally ingested a counterfeit tablet dropped on the floor by a family member. (more…)
Author Interviews, Pharmacology, Sleep Disorders / 14.06.2016 Interview with: Anna-Therese Lehnich Zentrum für Klinische Epidemiologie (ZKE) c/o Institut für Medizinische Informatik Biometrie undEpidemiologie (IMIBE) What is the background for this study? What are the main findings? Response: Sleep disturbances and their consequences are often underestimated but they are of high importance with respect to public health. We were interested in the question whether drugs labeled as sleep disturbing in the summary of product characteristics actually lead to more sleep disorders like difficulties falling asleep, difficulties maintaining sleep, and early morning arousal. To answer this question, we analyzed data of 4,221 persons from Germany. (more…)
ASCO, Author Interviews, Cancer Research, Geriatrics, Lymphoma, NYU, Pharmacology / 07.06.2016 Interview with: Dr. Catherine S. M. Diefenbach MD Assistant Professor of Medicine NYU Cancer Center New York, NY 10016 What is the background for this study? What are the main findings? Dr. Diefenbach: It is well known that age is important prognostic factor in non-Hodgkin’s lymphoma (NHL). Multiple studies have illustrated that elderly lymphoma patients have inferior survival outcomes as compared to their younger counterpart. While the tumor biology is often different in these two groups, and may play a role in this discordancy, elderly patients are often frail or have multiple medical comorbidities. These include geriatric syndromes, such as: cognitive impairment, falls, polypharmacy, and potentially inappropriate medication (PIM) use. All of these may contribute to poor outcomes for elderly patients. In addition, elderly patients are often under-treated for their aggressive lymphoma out of concern for toxicity or side effects, even though the data clearly demonstrates that elderly patients can still benefit from curative intent chemotherapy. (more…)
Author Interviews, Geriatrics, Pharmacology / 13.05.2016 Interview with: Leigh Purvis, MPA Director of Health Services Research AARP Public Policy Institute Editor’s Note: The May AARP Bulletin has a important article “Black Market Meds Are Flooding the Nation’s Pharmacies And Hospitals” by Joe Eaton, discussing the growing problem of counterfeit medications entering the US pharmaceutical supply chain. Ms. Leigh Purvis of the AARP Policy Institute discussed this important issue for the readers of Ms. Purvis’ areas of expertise include prescription drug pricing, biologic drugs, and Medicare prescription drug coverage. Is pharmaceutical theft and fraud a new or growing problem? Ms. Purvis: I think it’s safe to say that pharmaceutical theft is a growing problem. Skyrocketing prices have made pharmaceuticals a lucrative target for criminals. Trucks transporting pharmaceuticals are a common target, although some thieves have stolen prescription drugs directly from manufacturers’ warehouses. Pharmaceutical fraud is also a growing concern. FDA does a great deal to ensure the safety of US pharmaceuticals. However, problems can still arise, particularly when people purchase drugs online. (more…)
Author Interviews, Cost of Health Care, University of Pittsburgh / 03.06.2015

Julie M. Donohue, Ph.D. Associate professor and Vice Chair for Research Graduate School of Public Health Department of Health Policy and Management University of Interview with: Julie M. Donohue, Ph.D. Associate professor and Vice Chair for Research Graduate School of Public Health Department of Health Policy and Management University of Pittsburgh Medical Research: What is the background for this study? What are the main findings? Dr. Donohue: We looked at data on medication use from January through September 2014 on 1 million Affordable Care Act-established marketplace insurance plan enrollees. Our analysis found that among people who enrolled in individual marketplaces, those who enrolled earlier were older and used more medication than later enrollees. Marketplace enrollees, as a whole, had lower average drug spending per person and were less likely to use most medication classes than patients enrolled in employer-sponsored health insurance. However, marketplace enrollees were much more likely to use medicines for hepatitis C and for HIV, which is particularly important given the general concerns about the rising costs of these medications for consumers. (more…)
Author Interviews, PNAS, Statins / 04.03.2015

Professor Andrew W. Munro FRSC FSB Professor of Molecular Enzymology Manchester Institute of Biotechnology Faculty of Life Sciences University of Manchester Manchester Interview with: Professor Andrew W. Munro FRSC FSB Professor of Molecular Enzymology Manchester Institute of Biotechnology Faculty of Life Sciences University of Manchester Manchester UK MedicalResearch: What is the background for this study? What are the main findings? Dr. Munro: Statins are blockbuster drugs that inhibit the key enzyme in cholesterol synthesis: 3-beta-hydroxymethylglutaryl CoA reductase (HMG-CoA reductase), which catalyzes the rate-limiting step in the biosynthesis of cholesterol. As a consequence, statin drugs reduce levels of low-density lipoprotein (LDL-) cholesterol, are effective against hypercholesterolemia and reduce the risk of atherosclerosis and heart attack. One of the major statin drugs is pravastatin, which is derived from a fungal natural product called compactin. The process of conversion of compactin into pravastatin involves the use of an oxygen-inserting enzyme called a cytochrome P450 (or P450), which catalyzes the hydroxylation of compactin to form pravastatin. In order to produce a more cost-efficient and streamlined route to pravastatin production, our teams from the University of Manchester (UK) and DSM (Delft, The Netherlands) developed a single-step process for pravastatin production. This process involved harnessing the productive efficiency of an industrial strain of the beta-lactam (penicillin-type) antibiotic producing fungus Penicillium chrysogenum. The beta-lactam antibiotic genes were deleted from this organism, and replaced by those encoding for compactin biosynthesis (transferred from a different Penicillium species). This led to high level production of compactin, but also to substantial formation of a partially degraded (deacylated) form. To get around this problem and in order to further improve compactin production, the enzyme responsible for the deacylation (an esterase) was identified and the gene encoding this activity was deleted from the production strain. The final stages of development of the novel, one-step pravastatin production process involved the identification of a suitable P450 enzyme that could catalyze the required hydroxylation of compactin. A bacterial P450 was identified that catalyzed hydroxylation at the correct position on the compactin molecule. However, the stereoselectivity of the reaction was in favour of the incorrect isomer – forming predominantly epi-pravastatin over the desired pravastatin. This was addressed by mutagenesis of the P450 – ultimately leading to a variant (named P450Prava) that hydroxylated compactin with the required stereoselectivity to make pravastatin in large amounts. Determination of the structure of P450Prava in both the substrate-free and compactin-bound forms revealed the conformational changes that underpinned the conversion of the P450 enzyme to a pravastatin synthase. The expression of P450Prava in a compactin-producing strain of P. chrysogenum enabled pravastatin production at over 6 g/L in a fed-batch fermentation process, facilitating an efficient, single-step route to high yield generation of pravastatin. (more…)