Parkinson's Disease Psychosis and the Marketing of Pimavanserin.

In 2016, Nuplazid (pimavanserin) became the first FDA-approved treatment for Parkinson's Disease Psychosis (PDP). We explored the possibility that PDP was a term created to market Nuplazid. We examined trends in perceptions of psychosis in Parkinson's disease from the 1990s to 2020 through MEDLINE search term frequency, neurology textbooks, guidance from professional societies, Acadia annual reports, sponsored websites, and a sponsored meeting held by the National Institutes of Health (NIH). We analyzed continuing medical education (CME) activities on PDP and analyzed the connection between payments by the manufacturer of pimavanserin and prescriptions. Our analysis of nine sponsored CME activities reveals misleading themes, including: PDP is common, progressive, and not always drug-induced; there is no such thing as a benign hallucination, and psychotic symptoms always worsen; PDP increases mortality; and competing treatments are ineffective or dangerous while pimavanserin is safe and effective for treating PDP. Industry-sponsored CME was used to disseminate inaccurate and misleading marketing messages on psychosis related to Parkinson's disease. Some professional societies and some textbooks also resisted the PDP label. Reframing PDP as a unique condition is a typical example of condition branding. The establishment of PDP expanded the use of pimavanserin and is likely to have resulted in many avoidable deaths.

Are New Alzheimer Drugs Better Than Older Drugs?

This Viewpoint explores whether there are benefits to drugs targeting ß-amyloid protein in treating Alzheimer disease.

Pharmaceutical marketing: the example of drug samples.

Branded drug samples are one of the most important promotional tools that pharmaceutical manufactures employ. Pharmaceutical sales representatives ("drug reps") use samples to gain access to physicians and other prescribers. Sample provision is closely intertwined with visits by drug reps; detailing visits convince physicians to try new products, while sampling maintains the flow of prescriptions. Only drugs with the highest profit margins are sampled. Although physicians believe that samples save patients money, patients who receive samples have higher overall out-of-pocket costs. Most studies have found that patients in financial need are least likely to receive samples. Pharmaceutical marketers pitch samples as a low-risk way to deal with diagnostic uncertainty. In fact, there is no evidence that samples aid diagnosis. Sample availability may compromise patient safety by reducing compliance with guidelines and steering patients towards newer drugs, for which adverse effects have not been well-delineated. Although physicians believe that samples improve adherence for low-income patients, branded samples do not improve access or adherence Samples are not a charitable activity, but are instead a highly effective form of drug marketing. Sampling of branded drugs increase drug costs for everyone. Only a cohesive effort by clinicians, legislators and policymakers can end this practice. Evidence supports a ban on sample distribution of branded products.

Evergreened drugs or evergreened profits?

BACKGROUND: Branded drugs contribute disproportionately to high prescription drug spending. Pharmaceutical companies utilize patent extension "evergreening" techniques that contribute to high drug costs. AIMS: This article describes various patent extension techniques and analyzes the tactic of combining generic drugs with branded drugs, using metformin combinations for diabetes treatment as a case study. It examines the argument that FDCs enhance adherence and compares the cost of several branded fixed-dose combinations with the cost of their individual constituents. MATERIALS & METHODS: We reviewed literature on patent extension techniques in both medical and marketing literature, supplemented by our own extensive files. We performed a price analysis of several branded pharmaceuticals and generically available equivalents. Prescription drug prices were determined using GoodRx.com, and prices of over-the-counter products were established based on the prices of two chain wholesalers. Patent and formulation information was taken from the FDA Orange Book: Approved Drugs with Therapeutic Equivalence Evaluations database. RESULTS: "Evergreening" patent extension tactics include the sequential release of different formulations, minor dosing changes, and fixed-dose combinations (FDCs). A "new use" provides an opportunity for a company to re-patent, rebrand, and remarket one drug for multiple indications. It is unclear whether or not FDCs enhance adherence. Branded fixed-dose combinations generally cost far more than their individual constituents. FDCs that combine metformin with other drugs are an exception, often costing the same as the non-metformin component. DISCUSSION: Patent extension tactics increase drug costs while providing little additional benefit to patients. Minor alterations in formulations or dosing may provide no clinical benefits. Many FDCs are expensive and fail to provide cost-justified improvements in clinical outcomes, compared to equivalent generic drugs that would save money while delivering an equal standard of care. Combining newer hypoglycemic drugs with metformin, a gold-standard, generic, inexpensive drug, does not appear to cost more than individual constituents but offers no clinical advantage over metformin alone. CONCLUSION: Evergreening tactics should be reined in, as they represent significant cost to the healthcare system and to patients. Physicians and other prescribers should avoid prescribing FDCs, or slightly tweaked "new" drugs. Patented drug combinations generate profit without innovation.

Making the Case for Accelerated Withdrawal of Aducanumab.

The controversial approval in June 2021 by the Food and Drug Administration (FDA) of aducanumab (marketed as Aduhelm), Biogen's monoclonal antibody for patients with Alzheimer's disease, raises significant concerns for the dementia field and drug approval process, considering its lack of adequate evidence for clinical efficacy, safety issues, and cost. On 15 December 2021, an international group of clinicians, basic science experts, psychological and social science researchers, lay people with lived experience of dementia, and advocates for public health met to discuss making a recommendation for whether aducanumab's approval should be withdrawn. Attendees considered arguments both in favor of and in opposition to withdrawal and voted unanimously to recommend that the FDA withdraw its approval for aducanumab and to support the Right Care Alliance's filing of a formal Citizen Petition to this effect.

Survey of opioid prescribing among dentists indicates need for more effective education regarding pain management.

BACKGROUND: Dentists commonly prescribe opioids and are the highest prescribers of opioids to patients 18 years and younger. Little is known about dentists' beliefs regarding opioids and other analgesics. METHODS: The authors conducted a national survey of dentists about their opioid prescribing habits, perceptions regarding opioid effectiveness, beliefs about patient behaviors, and relationships with drug and equipment manufacturers. RESULTS: The authors received 291 responses from 30 states and 2 territories and analyzed 269 completed surveys. Although 84% of respondents reported believing that nonsteroidal anti-inflammatory drug (NSAID)-acetaminophen combinations are equally as effective or more effective than opioids, 43% of respondents also reported regularly prescribing opioid medications. Of those who reported prescribing opioids, 9 of 10 reported they were less likely to prescribe opioids to adolescents aged 11 through 18 years, but only 48% reported they were less likely to prescribe opioids to young adults aged 19 through 25 years. One-half of those who reported prescribing opioids reported prescribing in amounts that would result in unused medication, and 69% reported having had patients divert or misuse opioids. Few dentists reported industry interactions. CONCLUSIONS: The continued prescription of opioids contradicts mounting evidence about the superiority of NSAIDs over opioids in dentistry. Continuing dental education, increased use of prescription drug monitoring programs, and the development of national guidelines are necessary to align clinical practice with current evidence. PRACTICAL IMPLICATIONS: Dentists should seek to minimize opioid prescribing and pill counts and instead opt for safer, more effective NSAID-acetaminophen combinations. Dentists also should refrain from prescribing opioids to patients younger than 25 years because of the high risk of experiencing addiction in this population.

Increase your Confidence in Opioid Prescribing: Marketing Messages in Continuing Medical Education Activities on ER/LA Opioids.

BACKGROUND: Overprescription of opioids has fueled an epidemic of addiction and overdose deaths. The FDA required manufacturers of extended-release/long-acting (ER/LA) opioids to fund continuing medical education (CME) on opioids as part of a Risk Evaluation and Mitigation Strategy (REMS). OBJECTIVES: We sought to determine whether industry-funded REMS on long-acting opioids were consistent with the FDA's goal to reduce serious, adverse outcomes resulting from inappropriate prescribing, misuse, and abuse. STUDY DESIGN: In 2018, we analyzed all internet-based REMS CME activities funded by the REMS Program Companies (RPC), a consortium of ER/LA opioid manufacturers. METHODS: We utilized systematic narrative thematic analysis, an inductive approach that allows for mapping of concepts and meanings across a body of data by identifying, recording, analyzing, and refining key narrative points, called "themes". Authors viewed all REMS activities multiple times. RESULTS: Ten themes were identified, all of which were at least somewhat incongruent with federal guidelines and their goals: 1. Chronic pain is a common, under-treated problem. 2.Chronic pain is a chronic disease.3.Opioids are an appropriate treatment for chronic pain. 4.LAs are more appropriate than immediate-release (IR) opioids for chronic pain. 5.Tolerance is normal, expected, and beneficial. 6. Opioid rotation" can maximize analgesia and minimize adverse effects.7. There is no population for whom opioids are absolutely contraindicated or inappropriate. 8. Screening and monitoring tools are effective for preventing opioid-related problems. 9. Opioid related adverse effects, such as respiratory depression and addiction, are due only to misuse and abuse. Addiction, overdose, and death are due to street drugs such as heroin and fentanyl, not prescription opioids.Themes and statements repeated in these activities were inconsistent with current medical knowledge, evidence-based federal guidelines, and FDA goals. LIMITATIONS: We evaluated only online, not live, CME. We also did not evaluate individual conflicts of interest of faculty. CONCLUSIONS: Industry-funded REMS-compliant CME on opioids contain messages that misrepresent scientific evidence and may foster overprescribing of opioids.

A Ray of Sunshine: Transparency in Physician-Industry Relationships Is Not Enough.

Gifts from pharmaceutical and medical device companies to physicians in the United States have been reported since 2014, through the Physician Payments Sunshine Act. Although researchers have utilized these data to publish many studies on conflicts of interest (COIs) and prescribing behavior, there is no evidence that physician behavior regarding COI has changed, or that employers, meeting organizers, or medical journals are excluding physicians based on conflicts of interest. Disclosure is necessary but not sufficient to address the damage that industry relationships causes to medical knowledge and public health.

Changing Pharmaceutical Industry Interaction in US Family Medicine Residencies: A CERA Study.

BACKGROUND: Pharmaceutical interaction in US residencies is common. This study explores the extent and type of learner interactions in US family medicine residencies with the pharmaceutical industry and compares interactions from 2008, 2013, and 2019. METHODS: We surveyed program directors of 628 family medicine residencies with 8 questions using the 2019 Council of Academic Family Medicine Educational Research Alliance Survey and compared the responses to 2008 and 2013 results. RESULTS: The survey response rate was 39%; 81% of responding residencies did not allow food or gifts, 86% did not allow drug samples, 84% did not allow industry to interact with medical students or residents, and 81% did not allow industry-sponsored residency activities. These numbers were statistically significantly higher than both 2008 and 2013. In 2019, 151 responding programs (64%) were pharma-free, that is, they answered "No" to all 4 questions about interactions. Pharma-free residencies were increased in 2019 compared with 26% in 2008% and 49% in 2013. University-based family medicine programs were more likely to be pharma-free. Only 21% of responding programs had a formal curriculum that explores the interaction between physicians and the pharmaceutical industry. Factors cited for decreasing interaction included: institutional policy, ethical concerns, faculty input, and local response to national legislation. CONCLUSIONS: Interaction between trainees in US family medicine residencies and the pharmaceutical industry continued to decrease. A changing national legislative landscape combined with institutional policies and concerns about industry influence on prescribing habits may be important factors driving the limiting of interactions.

Marketing Messages in Continuing Medical Education (CME) Modules on Binge-Eating Disorder (BED).

BACKGROUND: In 2015, Vyvanse (lisdexamfetamine) became the first Food and Drug Administration (FDA)-approved treatment for binge-eating disorder (BED), a condition first recognized by the DSM-V in 2013. Because pharmaceutical companies use continuing medical education (CME) to help sell drugs, we explored possible bias in CME modules on BED. METHODS: We utilized a qualitative thematic analysis research approach to identify and classify patterns in CME activities focusing on BED. RESULTS: We identified 27 online CME activities on BED in 2015. All were funded by Shire, which manufactures lisdexamfetamine. Seven of 16 presenters disclosed financial ties with Shire. Twenty-nine slides recurred in at least 2 CME modules, and 12 slides were repeated in 5 or more modules. Diagnosis-related themes included: BED is a real, treatable disease; BED is highly prevalent but often missed; BED can occur in anyone; BED results in poor quality of life; many patients with BED are obese; and BED makes losing weight difficult. Treatment-related themes included: lisdexamfetamine is highly effective; topiramate is limited by substantial adverse effects; and other therapeutic options for BED are inferior to lisdexamfetamine because they do not cause weight loss. Although amphetamines can cause addiction, myocardial infarction, stroke, and death, no module mentioned these serious adverse effects. CONCLUSIONS: It seems that CME is being used to promote lisdexamfetamine for weight loss (a contraindicated use) and to highlight benefits of lisdexamfetamine while underplaying the risks.

Pharmaceutical Ethics and Grassroots Activism in the United States: A Social History Perspective.

Women's health activists laid the groundwork for passage of the law that created the U.S. Food and Drug Administration in 1906. The pharmaceutical and food industries fought regulatory reforms then and continue to do so now. We examine public health activism in the Progressive Era, the postwar era and the present day. The women's health movement began in the 1960s, and criticized both the pharmaceutical industry and the medical establishment. In the 1990s, patient advocacy groups began accepting industry funds; thousands of commercially-funded groups now dominate the advocacy landscape. As pharma funding became normalized, concerns arose regarding a) the lack of transparency and public accountability regarding funding, b) the distortion of groups' agendas, and c) the ability of pharma-funded groups to dominate the discourse and override less well-resourced patient and health advocacy groups. Although industry-funded groups argue that funding allows them to provide useful services, the trade-off in health risks, exorbitant prices and distorted information is far too high. Sincerity is beside the point; patients and the industry have differing interests when it comes to drug safety and efficacy, drug information and drug prices. A growing resistance movement is asserting the values of its activist predecessors and opposing the prevailing culture of pharma-funded advocacy.

How drug companies manipulate prescribing behavior / Cómo las empresas farmacéuticas manipulan la conducta para formular los medicamentos

Abstract Pharmaceutical companies affect prescribing behavior through various means, including pharmaceutical salespeople (drug reps), drug samples, influential peers, and educational events. Information on drugs provided by industry representatives has been shown to be inaccurate. Drug samples are among the most effective marketing tools that companies have. "Thought leaders" or "key opinion leaders" are used to persuade peers to use drugs for unapproved uses, raise awareness of targeted diseases, and to shape perceptions of a drug's benefits and harms, as well as perceptions about competing drugs. Although grants provided for talks, seminars, and meetings are described as "unrestricted," it is understood that the company gets to select some speakers, and that speakers with views that undermine marketing messages will not be invited. Promotion has been shown to increase physicians' prescription of targeted drugs, and increases prescription costs.

Resumen Las empresas farmacéuticas influyen sobre la conducta para formular los medicamentos de diversas formas, incluyendo a los vendedores de las empresas farmacéuticas (representantes de medicamentos), las muestras de medicamentos, pares influyentes y eventos educativos. La información sobre los medicamentos suministrada por los representantes de la industria ha demostrado ser inexacta. Las muestras de medicamentos son una de las herramientas de mercadeo más efectivas con que cuentan las empresas. Se recurre a "Los líderes de pensamiento" o a los "principales líderes de opinión" (KOLs por sus siglas en inglés) para convencer a sus pares de que utilicen medicamentos para usos no aprobados, sensibilizar sobre patologías objetivo, y conformar percepciones sobre los beneficios y perjuicios de un medicamento, además de crear impresiones sobre medicamentos en competencia. A pesar de que se dice que las asignaciones monetarias para dictar charlas, celebrar seminarios y reuniones no deben tener restricciones, es claro que la empresa selecciona determinados conferencistas y que aquellos cuyas opiniones socaven los mensajes de mercadeo no serán invitados. Se ha demostrado que la promoción aumenta la prescripción de medicamentos específicos y aumenta los costos de esta.

Influence of pharmaceutical marketing on Medicare prescriptions in the District of Columbia.

IMPORTANCE: Gifts from pharmaceutical companies are believed to influence prescribing behavior, but few studies have addressed the association between industry gifts to physicians and drug costs, prescription volume, or preference for generic drugs. Even less research addresses the effect of gifts on the prescribing behavior of nurse practitioners (NPs), physician assistants (PAs), and podiatrists. OBJECTIVE: To analyze the association between gifts provided by pharmaceutical companies to individual prescribers in Washington DC and the number of prescriptions, cost of prescriptions, and proportion of branded prescriptions for each prescriber. DESIGN: Gifts data from the District of Columbia's (DC) AccessRx program and the federal Center for Medicare and Medicaid Services (CMS) Open Payments program were analyzed with claims data from the CMS 2013 Medicare Provider Utilization and Payment Data. SETTING: Washington DC, 2013. PARTICIPANTS: Physicians, nurse practitioners, physician assistants, podiatrists, and other licensed Medicare Part D prescribers who participated in Medicare Part D (a Federal prescription drug program that covers patients over age 65 or who are disabled). EXPOSURE(S): Gifts to healthcare prescribers (including cash, meals, and ownership interests) from pharmaceutical companies. MAIN OUTCOMES AND MEASURES: Average number of Medicare Part D claims per prescriber, number of claims per patient, cost per claim, and proportion of branded claims. RESULTS: In 2013, 1,122 (39.1%) of 2,873 Medicare Part D prescribers received gifts from pharmaceutical companies totaling $3.9 million in 2013. Compared to non-gift recipients, gift recipients prescribed 2.3 more claims per patient, prescribed medications costing $50 more per claim, and prescribed 7.8% more branded drugs. In six specialties (General Internal Medicine, Family Medicine, Obstetrics/Gynecology, Urology, Ophthalmology, and Dermatology), gifts were associated with a significantly increased average cost of claims. For Internal Medicine, Family Medicine, and Ophthalmology, gifts were associated with more branded claims. Gift acceptance was associated with increased average cost per claim for PAs and NPs. Gift acceptance was also associated with higher proportion of branded claims for PAs but not NPs. Physicians who received small gifts (less than $500 annually) had more expensive claims ($114 vs. $85) and more branded claims (30.3% vs. 25.7%) than physicians who received no gifts. Those receiving large gifts (greater than $500 annually) had the highest average costs per claim ($189) and branded claims (39.9%) than other groups. All differences were statistically significant (p<0.05). CONCLUSIONS AND RELEVANCE: Gifts from pharmaceutical companies are associated with more prescriptions per patient, more costly prescriptions, and a higher proportion of branded prescriptions with variation across specialties. Gifts of any size had an effect and larger gifts elicited a larger impact on prescribing behaviors. Our study confirms and expands on previous work showing that industry gifts are associated with more expensive prescriptions and more branded prescriptions. Industry gifts influence prescribing behavior, may have adverse public health implications, and should be banned.

Testosterone and sexual function.

PURPOSE OF REVIEW: Testosterone therapy has been advocated in the treatment of symptoms that may represent normal aging. We briefly review randomized clinical trials on the effects of testosterone therapy on sexual function. RECENT FINDINGS: About half of clinical trials showed no benefit of testosterone therapy on any aspect of sexual function. In those studies showing a benefit on some aspect of sexual function, most sexual function domains were not improved. Testosterone therapy has been disappointing in the treatment of erectile dysfunction. Potential risks of therapy include an increase in thromboembolic and other cardiovascular diseases. SUMMARY: The limited and inconsistent benefits of testosterone therapy for sexual function argue against use of this therapy in aging men, including those with 'low testosterone'.

Pharmacist-industry relationships.

OBJECTIVES: The purpose of this study was to document, in their own words, beliefs and attitudes that American pharmacists have towards the pharmaceutical industry and pharmacists' interactions with industry. METHODS: An ethnographic-style qualitative study was conducted utilizing open-ended interviews with four hospital pharmacists, two independent pharmacists, two retail pharmacists and one administrative pharmacist in the Washington, DC, metropolitan area to elicit descriptions of and attitudes towards pharmacists' relationships with industry. Analysis of the qualitative material followed established ethnographic conventions of narrative thematic analysis. KEY FINDINGS: All pharmacists reported interactions with pharmaceutical company representatives. Most had received free resources or services from industry, including educational courses. Respondents uniformly believed that industry promotional efforts are primarily directed towards physicians. Although respondents felt strongly that drug prices were excessive and that 'me-too' drugs were of limited use, they generally had a neutral-to-positive view of industry-funded adherence/compliance programmes, coupons, vouchers, and copay payment programmes. Interviewees viewed direct-to-consumer advertising negatively, but had a generally positive view of industry-funded drug information. CONCLUSIONS: Pharmacists may represent a hitherto under-identified cohort of health professionals who are targeted for industry influence; expanding roles for pharmacists may make them even more attractive targets for future industry attention. Pharmacy schools should ensure that students learn to rely on unbiased information sources and should teach students about conflicts of interest and the risks of interacting with industry. Further research should be conducted on the extent to which pharmacists' attitudes towards their duties and towards drug assessment and recommendation are influenced by the pharmaceutical industry.

Treatment of Men for "Low Testosterone": A Systematic Review.

Testosterone products are recommended by some prescribers in response to a diagnosis or presumption of "low testosterone" (low-T) for cardiovascular health, sexual function, muscle weakness or wasting, mood and behavior, and cognition. We performed a systematic review of 156 eligible randomized controlled trials in which testosterone was compared to placebo for one or more of these conditions. We included studies in bibliographic databases between January 1, 1950 and April 9, 2016, and excluded studies involving bodybuilding, contraceptive effectiveness, or treatment of any condition in women or children. Studies with multiple relevant endpoints were included in all relevant tables. Testosterone supplementation did not show consistent benefit for cardiovascular risk, sexual function, mood and behavior, or cognition. Studies that examined clinical cardiovascular endpoints have not favored testosterone therapy over placebo. Testosterone is ineffective in treating erectile dysfunction and controlled trials did not show a consistent effect on libido. Testosterone supplementation consistently increased muscle strength but did not have beneficial effects on physical function. Most studies on mood-related endpoints found no beneficial effect of testosterone treatment on personality, psychological well-being, or mood. The prescription of testosterone supplementation for low-T for cardiovascular health, sexual function, physical function, mood, or cognitive function is without support from randomized clinical trials.