Conflict of interest policies at Australian medical schools.

BACKGROUND: Pharmaceutical industry exposure is widespread during medical training and may affect education and clinical decision-making. Medical faculties' conflict of interest (COI) policies help to limit this exposure and protect students against commercial influence. AIMS: Our aim was to investigate the prevalence, content and strength of COI policies at Australian medical schools and changes since a previous assessment conducted in 2009. METHODS: We identified policies by searching medical school and host university websites in January 2021, and contacted deans to identify any missed policies. We applied a modified version of a scorecard developed in previous studies to examine the content of COI policies. All data were coded in duplicate. COI policies were rated on a scale from 0 (no policy) to 2 (strong policy) across 11 items per medical school. Oversight mechanisms and sanctions were also assessed, and current policies were compared with the 2009 study. RESULTS: Of 155 potentially relevant policies, 153 were university-wide and two were specific to medical schools. No policies covered sales representatives, on-site sponsored education or free samples. Oversight of consultancies had improved substantially, with 76% of schools requiring preapproval. Disclosure policies, while usually present, were weak, with no public disclosure required. CONCLUSION: We found little indication that Australian medical students are protected from commercial influence on medical education, and there has been limited COI policy development within the past decade. More attention is needed to ensure the independence of medical education in Australia.

Factors relating to nonpublication and publication bias in clinical trials in Canada: A qualitative interview study.

AIMS: This study aims to understand factors contributing to nonpublication and publication bias in clinical trials in Canada. METHODS: Qualitative interviews were conducted between March 2019 and April 2021 with 34 participants from the Canadian provinces of Alberta, British Columbia and Ontario, including 17 clinical trial investigators, 1 clinical research coordinator, 3 research administrators, 3 research ethics board members and 10 clinical trial participants. We conducted a thematic analysis involving coding of interview transcripts and memo-writing to identify key themes. RESULTS: Several factors contribute to nonpublication and publication bias in clinical trial research. A core theme was that reporting practices are shaped by incentives within the research system taht favour publication of positive over negative trials. Investigators are discouraged from reporting by experiences or perceptions of difficulty in publishing negative findings but rewarded for publishing positive findings in various ways. Trial investigators more strongly associated positive clinical trials than negative trials with opportunities for industry and nonindustry funding and with academic promotion, bonuses and recognition. Research institutions and ethics boards tended to lack well-resourced, proactive policies and practices to ensure trial findings are reported in registries or journals. CONCLUSION: Clinical trial reporting practices in Canada are shaped by incentives favouring reporting of positive over negative trials, such as funding opportunities and academic promotion, bonuses and recognition. Research institutions could help change incentives by adopting performance metrics that emphasize full reporting of results in journals or registries.

Interactions with the pharmaceutical industry and the practice, knowledge and beliefs of medical oncologists and clinical haematologists: a systematic review.

BACKGROUND: No previous review has assessed the extent and effect of industry interactions on medical oncologists and haematologists specifically. METHODS: A systematic review investigated interactions with the pharmaceutical industry and how these might affect the clinical practice, knowledge and beliefs of cancer physicians. MEDLINE, Embase, PsycINFO and Web of Science Core Collection databases were searched from inception to February 2021. RESULTS: Twenty-nine cross-sectional and two cohort studies met the inclusion criteria. These were classified into three categories of investigation: (1) extent of exposure to industry for cancer physicians as whole (n = 11); (2) financial ties among influential cancer physicians specifically (n = 11) and (3) associations between industry exposure and prescribing (n = 9). Cancer physicians frequently receive payments from or maintain financial ties with industry, at a prevalence of up to 63% in the United States (US) and 70.6% in Japan. Among influential clinicians, 86% of US and 78% of Japanese oncology guidelines authors receive payments. Payments were associated with either a neutral or negative influence on the quality of prescribing practice. Limited evidence suggests oncologists believe education by industry could lead to unconscious bias. CONCLUSIONS: There is substantial evidence of frequent relationships between cancer physicians and the pharmaceutical industry in a range of high-income countries. More research is needed on clinical implications for patients and better management of these relationships. REGISTRATION: PROSPERO identification number CRD42020143353.

Association Between Conflicts of Interest and Authors' Positions on Harms of Varenicline: a Cross-Sectional Analysis.

BACKGROUND: Few studies have investigated the relationship between industry funding/conflicts of interest and authors' positions in opinion pieces on drug safety. Harmful effects of varenicline, a treatment for smoking cessation, have been highly contested. OBJECTIVE: To examine the association between pharmaceutical industry funding/authors' financial conflicts of interest and position on varenicline in opinion articles, especially in relation to the minimization of harms; to assess whether opinion pieces on drug safety issues written by authors with conflicts of interest are more frequently cited in the news or social media. DESIGN: Cross-sectional analysis. PARTICIPANTS: English language opinion pieces and narrative reviews about varenicline published between May 2006 and February 2019. MAIN MEASURES: Odds ratios and 95% confidence intervals; the Mann-Whitney two-sample statistic was used to test for differences in Altmetric scores, a measure of media attention. KEY RESULTS: Of the 221 included articles, 30.3% (67) disclosed the funding source and 62.9% (139) disclosed authors' conflicts of interest. Authors of opinion pieces on varenicline who reported financial ties to the pharmaceutical industry (as a conflict of interest or funding source) were more likely to minimise the cardiovascular and psychiatric risk of varenicline compared to those without conflicts of interest or industry funding (OR: 4.00; 95% CI: 1.32 to 12.16 for cardiovascular risk; OR: 8.51; 95% CI: 3.79 to 19.11 for psychiatric risk). These associations persisted in sensitivity analyses. No statistically significant difference in Altmetric score was found between articles with (mean 15.83, median 3) and without (mean 11.90, median 1) conflicts of interest, indicating similar media attention (p-value=0.11). CONCLUSIONS: We found that authors with financial ties to drug companies were more likely to publish opinion pieces that minimised harms of varenicline. These results raise questions about journals' editorial policies to accept reviews of treatments from authors with financial relationships with manufacturers.

Regulatory authority and clinical acceptability: Physicians' responses to regulatory drug safety warnings.

AIMS: Medicines regulators issue post-market safety warnings to advise of newly uncovered risks, but with mixed impacts. We aimed to identify factors influencing the use of regulatory warnings by primary care and specialist physicians in the US and Australia. METHODS: Semi-structured qualitative interviews were carried out with 40 primary care physicians, endocrinologists and other generalist specialists in Boston (USA) and Australia. Coding and analysis were performed inductively and iteratively to identify and examine key factors. Analysis centred around four areas: physicians' awareness of drug safety information, preferred information sources, opinion-forming and sharing of information with patients. RESULTS: Uncertainty, trust and clinical authority emerged as factors influencing use of advisories. Although regulators were trusted as authoritative institutions, they appeared to lack clinical authority, and physicians validated regulatory information against other trusted sources including evidence, expert opinion and experience. Specialists became aware of drug safety issues through specialised literature, using evidence and clinical consensus to form opinions. Primary care physicians, fielding high volumes of information, relied on convenient, accessible information sources including the media and the "clinical grapevine" for awareness, and on clinical colleagues, specialists and experience for interpretation. Communicating risk to patients was complicated by uncertainty; physicians tailored information to patients' health literacy and information needs. US physicians were more aware of their national regulator's post-market safety role than Australian physicians of theirs. CONCLUSION: Drug safety warnings may not be optimally received or used. Regulators should consider strategies that increase trust, clinical relevance and accessibility, and address physicians' needs in communicating risk to patients.

Pioglitazone use in Australia and the United Kingdom following drug safety advisories on bladder cancer risk: An interrupted time series study.

PURPOSE: National regulators in Australia and the United Kingdom issued safety advisories on the association between pioglitazone use and bladder cancer in July 2011. The Australian advisory noted that males were at higher risk of bladder cancer than females, while the UK advisory highlighted a new recommendation, suggest careful consideration in the elderly due to increasing risk with age. This study examined whether these differences in the advisories had different age- and sex-based impacts in each country. METHODS: Interrupted time series analysis was used to compare pioglitazone use (prescriptions/100000 population) in Australia and the United Kingdom for the 24 months before and 11 months after the July 2011 safety advisories (study period July 2009-June 2012). Separate models were used to compare use by sex and age group (≥65 years vs. <65 years) in each country. RESULTS: Pioglitazone use fell in Australia (17%) and the United Kingdom (24%) following the safety advisories. Use of pioglitazone fell more for males (18%) than females (16%) in Australia, and more for females (25%) than males (23%) in the United Kingdom; however, neither difference was statistically significant (Australia p = 0.445, United Kingdom p = 0.462). Pioglitazone use fell to a similar extent among older people than younger people in the United Kingdom (23% vs. 26%, p = 0.354), and did not differ between age groups in Australia (both 18%, p = 0.772). CONCLUSIONS: The results indicate that differences in the Australian and UK safety advisories resulted in substantial reductions in pioglitazone use at the population level in both countries, however, differences by sub-groups were not observed.

"There are ways drug companies will get into DTC decisions": How Australian drug and therapeutics committees address pharmaceutical industry influence.

AIMS: One tool for protecting quality use of medicines in hospitals is a drug and therapeutics committee (DTC) that oversees medicines availability. Pharmaceutical industry marketing to prescribers is associated with less appropriate prescribing and increased costs. There is little data on decision-making practices of DTCs so it is unknown whether or how they might be vulnerable to pharmaceutical industry influence. This project explores DTC decision-making with a focus on how pharmaceutical industry influence on access and use of medicines is identified and managed. METHODS: We used a qualitative methodology with individual interviews of 29 participants who were current or recent members of public hospital DTCs across New South Wales, Australia. Participants included medical, pharmacy and nursing staff and 1 citizen. Committees were linked to specific hospitals or regions, and some were affiliated with paediatric, neonatal, rural or mental health services. RESULTS: Drug committee processes for oversight of medicines in public hospitals are vulnerable to pharmaceutical industry influence at several points. Applications for formulary additions are sometimes initiated and completed by company representatives. Conflict of interest disclosures among applicants and committee members may be incomplete. In some institutions, medicines are available from pharmaceutical companies without committee review, including through free samples and industry-supported medicines access programmes. Participants noticed the presence and impact of pharmaceutical company marketing activities to local clinicians, resulting in increased prescriber demand for products. CONCLUSION: Improved DTC practices and review of hospital policies concerning pharmaceutical marketing activities might preserve the independence of evidence-based decision-making for safe, cost-effective prescribing.

Industry payments to Australian medical oncologists and clinical haematologists: a cross-sectional analysis of publicly available disclosures.

BACKGROUND: Payments to medical oncologists and clinical haematologists can negatively affect prescribing practice, but the extent of payments to these specialists is unknown in Australia. AIMS: To analyse the extent of payments from the pharmaceutical industry to Australian cancer physicians as reported during the first collated period of the Disclosure Australia website. METHODS: We performed a retrospective, cross-sectional analysis of payments made from November 2018 to April 2019, using a file downloaded from the Disclosure Australia website. We checked the names of listed medical practitioners against Medical Board of Australia records to assign specialties. The number of medical oncologists, clinical haematologists, other specialist physicians and non-specialist physician medical practitioners was calculated, along with the payments to each of these groups. RESULTS: A total of A$7 332 407 was paid to 2775 medical practitioners. Of these, 236 were medical oncologists, 189 were haematologists and 1145 were other specialist physicians. This represents 31.7% of Australian medical oncologists and 30.9% of Australian haematologists, compared with 11.7% of all other specialist physicians and 1.1% of all other non-specialist physician medical practitioners. Medical oncologists received significantly higher payments (median A$2131.26) than other specialist physicians (median A$1376.00, 2-tailed P = 0.004) and other medical practitioners (median A$709.00, 2-tailed P < 0.001), while haematologists received significantly higher payments (median A$1519.95) than other medical practitioners (2-tailed P < 0.001), but similar payments to other specialist physicians (2-tailed P = 0.08). CONCLUSIONS: Australian cancer physicians receive payments at a higher proportional frequency and in greater dollar amounts than other specialist physicians and other medical practitioners in general.

Media coverage of drug regulatory agencies' safety advisories: A case study of citalopram and denosumab.

AIMS: Drug regulators issue safety advisories to warn clinicians and the public about new evidence of harmful effects of medicines. It is unclear how often these messages are covered by the media. Our aim was to analyse the extent of media coverage of two medicines that were subject to safety advisories from 2007 to 2016 in Australia, Canada, the United Kingdom and the United States. METHODS: Two medicines widely used to treat mental health or physical conditions were selected: citalopram and denosumab. Media reports were identified by searching LexisNexis and Factiva. Reports were included if they stated at least one health benefit or harm. A content analysis of the reports was conducted. RESULTS: In total, 195 media reports on citalopram and 239 on denosumab were included. For citalopram, 43.1% (84/195) of the reports mentioned benefits, 85.6% (167/195) mentioned harms and 9.7% (19/195) mentioned the harm described in the advisories (cardiac arrhythmia). For denosumab, 94.1% (225/239) of the reports mentioned benefits and 39.7% (95/239) mentioned harms. The harms described in the advisories were rarely mentioned: 10.9% (26/239) of the reports mentioned osteonecrosis and ≤5% mentioned any of the other harms (atypical fractures, hypocalcaemia, serious infections and dermatologic reactions). CONCLUSIONS: We found limited media coverage of the harms highlighted in safety advisories. Almost two-thirds of the media stories on denosumab did not include any information about harms, despite the many advisories during this time frame. Citalopram coverage covered harms more often but rarely mentioned cardiac arrhythmias. These findings raise questions about how to better ensure that regulatory risk communications reach the general public.

A descriptive analysis of medicines safety advisories issued by national medicines regulators in Australia, Canada, the United Kingdom and the United States - 2007 to 2016.

PURPOSE: To determine the frequency and characteristics of safety advisories issued by medicines regulatory agencies in Australia, Canada, United Kingdom (UK) and the United States (US). METHODS: This retrospective analysis examines medicines safety warnings issued by the US Food and Drug Administration (FDA), Health Canada (HC), the Australian Therapeutic Goods Administration (TGA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA) from January 1, 2007 until December 31, 2016. A database of warnings obtained from regulators' websites was developed and warnings were classified by communication type, drug, or therapeutic class focus, and the risk discussed. Advisories identifying the same drug or therapeutic class and risk were combined into groups termed "drug-risk issues" for comparisons between regulators. RESULTS: Over this 10-year period, 1441 advisories were identified, with the MHRA issuing the most advisories (MHRA = 469, FDA = 382, HC = 370 TGA = 220). Seventy two percent focussed on single drugs (1034/1441) and 58.7% were alerts (846/1441) posted on the regulators' websites. Diabetes drugs, smoking cessation drugs and immunomodulatory agents were the individual drug types most often subject to safety advisories, while antidepressants, antipsychotics, and proton-pump inhibitors were the top three therapeutic classes. Of 680 identified drug-risk issues, 3.8% (26/680) described a risk of death. By body system, cardiac effects were the most frequent: 10.4% (71/680). CONCLUSION: We found considerable differences in the use of advisories including frequency, communication type, and focus. Disparities in communication about emergent evidence on risks may mean that clinicians and patients in some countries are less well informed about medicine safety concerns than others.

Correction to: Medical, pharmacy and nursing students in the Baltic countries: interactions with the pharmaceutical and medical device industries.

Following publication of the original article [1], we have been notified that the publication is missing a link to the data repository.

Medical, pharmacy and nursing students in the Baltic countries: interactions with the pharmaceutical and medical device industries.

BACKGROUND: Interactions between pharmaceutical and medical device industries and students can lead to commercial influences on educational messages, with a potential to bias future treatment choice. This is the first study in the Baltic countries describing exposure and attitudes of medical, pharmacy and nursing students towards cooperation with industry. METHODS: A cross-sectional on-line survey of current medical, pharmacy and nursing students (n = 918) in three Baltic countries was carried out. RESULTS: We found that most students participate in events organized or sponsored by industry and accept a range of gifts and benefits. Students in the Baltic countries consider cooperation with industry important; at the same time, most do not feel that they have sufficient training on how to ethically interact with pharmaceutical and medical device companies and believe that these interactions can influence their prescribing or dispensing patterns. There is a tendency to rationalize cooperation with industry by referring to the current economic situation and patient benefits. Pharmacy students have higher rates of participation and they accept gifts and other benefits more often than nursing or medical students; therefore, they are likely to be more vulnerable to potential industry influence. CONCLUSIONS: The findings highlight the need to include topics on ethics and conflicts of interests in cooperation with industry in curriculum of health care students in Baltic countries. Without proper training, students continue to be at risk to industry influence and may develop habits for their further practice differing from evidence-based practice in prescribing and dispensing of medicines, as well as use of medical devices.

Secret safety warnings on medicines: A case study of information access requests.

PURPOSE: There has been less attention to the transparency of postmarket evidence of harmful effects of medicines than of premarket clinical trial data. This is a case study of requests for Australian "direct health professional communications" (DHPCs). These letters are used by regulators and manufacturers to inform clinicians of emergent evidence of harm. DHPCs are not made public by Australia's Therapeutic Goods Administration (TGA). METHODS: We requested all DHPCs sent out in Australia from 2007 to 2016 inclusive for 207 drugs that were subject to safety advisories over this decade in Canada, the United Kingdom, and/or the United States. We contacted 39 manufacturers (February to May 2018), with repeat requests to nonrespondents, and a follow-up freedom-of-information (FOI) request to the TGA. RESULTS: Fifteen companies provided information, either sending DHPCs (n = 4, on five drugs) or affirming none were sent out (n = 11). The remaining 24 of 39 (62%) companies did not provide DHPCs: nine (23%) refused the request, often citing commercial confidentiality; the rest provided no answer despite repeat requests. In total, we had no information for 170 of 207 (82%) of the drugs. Our FOI request to the TGA was unsuccessful. CONCLUSIONS: Our experience highlights unacceptable secrecy concerning safety warnings previously sent to thousands of Australian clinicians. In the absence of explicit regulatory policy supporting disclosure, companies differed in their response. These letters warn of serious and often life-threatening harm and guide safer care; full ongoing public access is needed, ideally in searchable online databases.

Medicines Information and the Regulation of the Promotion of Pharmaceuticals.

Many factors contribute to the inappropriate use of medicines, including not only a lack of information but also inaccurate and misleading promotional information. This review examines how the promotion of pharmaceuticals directly affects the prescribing and use of medicines. We define promotion broadly as all actions taken directly by pharmaceutical companies with the aim of enhancing product sales. We look in greater detail at promotion techniques aimed at prescribers, such as sales representatives, pharmaceutical advertisements in medical journals and use of key opinion leaders, along with the quality of information provided and the effects thereof. We also discuss promotion to the public, through direct-to-consumer advertising, and its effects. Finally, we consider initiatives to regulate promotion that come from industry, government and nongovernmental organizations.

Mental Health Messages in Prominent Mental Health Apps.

PURPOSE: Many who seek primary health care advice about mental health may be using mobile applications (apps) claiming to improve well-being or relieve symptoms. We aimed to identify how prominent mental health apps frame mental health, including who has problems and how they should be managed. METHODS: We conducted a qualitative content analysis of advertising material for mental health apps found online in the United States, the United Kingdom, Canada, and Australia during late 2016. Apps were included if they explicitly referenced mental health diagnoses or symptoms and offered diagnosis and guidance, or made health claims. Two independent coders analyzed app store descriptions and linked websites using a structured, open-ended instrument. We conducted interpretive analysis to identify key themes and the range of messages. RESULTS: We identified 61 mental health apps: 34 addressed predominantly anxiety, panic, and stress (56%), 16 addressed mood disorders (26%), and 11 addressed well-being or other mental health issues (18%). Apps described mental health problems as being psychological symptoms, a risk state, or lack of life achievements. Mental health problems were framed as present in everyone, but everyone was represented as employed, white, and in a family. Explanations about mental health focused on abnormal responses to mild triggers, with minimal acknowledgment of external stressors. Therapeutic strategies included relaxation, cognitive guidance, and self-monitoring. Apps encouraged frequent use and promoted personal responsibility for improvement. CONCLUSIONS: Mental health apps may promote medicalization of normal mental states and imply individual responsibility for mental well-being. Within the health care clinician-patient relationship, such messages should be challenged, where appropriate, to prevent overdiagnosis and ensure supportive health care where needed.

Disease awareness campaigns in printed and online media in Latvia: cross-sectional study on consistency with WHO ethical criteria for medicinal drug promotion and European standards.

BACKGROUND: European legislation prohibits direct-to-consumer advertising of prescription medicines, but allows drug manufacturers to provide information to the public on health and diseases. Our aim was to measure the frequency of disease awareness campaigns in Latvian media and assess their compliance with international and European standards. METHODS: Materials on health/disease and treatments were collected between April and September 2015 from 12 newspapers and magazines and six online portals. Disease awareness campaigns were assessed using a previously developed instrument based on the WHO Ethical Criteria for Medicinal Drug promotion and European standards (EU law and pharmaceutical industry self-regulatory guidelines). Collected materials were used to examine the information provided on medical conditions and their diagnosis and treatment. The inter-rater reliability was calculated. RESULTS: We collected 263 materials from print (n = 149) and online media (n = 114); 94 were news items and 169 were disease-awareness advertisements. Cancer, cardiovascular problems, allergies and respiratory diseases were common topics. Of the 157 campaigns assessed, non-compliance was identified in 149 cases (inter-rater reliability 90%), mainly due to misleading or incomplete information, lack of balance and the absence of a listed author/sponsor. Six disease awareness campaigns directly mentioned a pharmaceutical product by brand name and other four included the logo or name of a manufacturer, referred to a condition and indirectly mentioned a treatment, all in contravention with European law. CONCLUSIONS: The compliance of disease awareness campaigns in Latvian media with international and European standards is low. This raises concerns about the nature of information being conveyed. Through lack of balance, missing sponsorship information, and misleading or incomplete information, these campaigns could contribute to inaccurate self-diagnosis and generate demand among those who might not need medical treatment.

Unwarranted claims of drug efficacy in pharmaceutical sales visits: are drugs approved on the basis of surrogate outcomes promoted appropriately?

AIMS: This study compares physicians' recall of the claims of benefits on cardiovascular disease and diabetes made by pharmaceutical sales representatives for drugs approved on the basis of a surrogate outcome, i.e., an off-label claim, compared with those approved on the basis of a serious morbidity or mortality (clinical) outcome. METHODS: Physicians in primary care practices in Montreal, Vancouver, Sacramento and Toulouse, who saw sales representatives as part of their usual practice and served a non-referral population, were contacted in blocks of 25 from a randomized list of all physicians practising in the relevant metropolitan area. We compared how frequently physicians reported that sales reps made claims of serious morbidity or mortality (clinically meaningful) benefits for drugs approved on the basis of surrogate outcomes vs. drugs approved on the basis of clinical outcomes. RESULTS: There were 448 promotions for 58 unique brand name cardiovascular and diabetes drugs. Claims of clinically meaningful benefit were reported in 156 (45%) of the 347 promotions for surrogate outcome drugs, constituting unwarranted efficacy claims, i.e., off-label promotion. Claims of clinical benefit were reported in 72 of the 101 promotions (71%) for drugs approved on the basis of clinical outcomes, adjusted OR = 0.3 (95% CI 0.2, 0.6), P < 0.001. CONCLUSIONS: Claims of efficacy made in sales visit promotions for drugs approved only on the basis of surrogate outcomes extended beyond the regulator-approved efficacy information for the product in almost half of promotions. Unapproved claims of drug efficacy constitute a form of off-label promotion and merit greater attention from regulators.