Open Access Research BMJ Open: first published as 10.1136/bmjopen-2017-019027 on 13 February 2018. Downloaded from Does industry-sponsored education foster overdiagnosis and overtreatment of depression, osteoporosis and over active bladder syndrome? An Australian cohort study
Barbara Mintzes,1 Swestika Swandari,2 Alice Fabbri,1,3 Quinn Grundy,1 Ray Moynihan,4 Lisa Bero1
This article has received a Abstract Strengths and limitations of this study badge for Open data. Objectives To investigate patterns of industry-sponsored educational events that focus on specific health conditions To cite: Mintzes B, Swandari S, ►► Australia’s transparency reports of industry funding for which there are concerns about overdiagnosis and Fabbri A, et al. Does industry- of health professionals were unique internationally overtreatment. sponsored education foster until 2015, in that the focus was on sponsored Design and setting This retrospective cohort study overdiagnosis and overtreatment events. of depression, osteoporosis examines publicly reported industry-sponsored events ►► This is the first data-driven national analysis of and overactive bladder in Australia from October 2011 to September 2015 for condition-specific industry educational event syndrome? An Australian three conditions potentially subject to overdiagnosis and sponsorship for overdiagnosed and overtreated cohort study. BMJ Open overtreatment: depression, osteoporosis and overactive conditions. 2018;8:e019027. doi:10.1136/ bladder. We used a database of transparency reports to ►► Classification of events was blinded to sponsor, bmjopen-2017-019027 identify events with a focus on depression, osteoporosis attendee characteristics and event descriptions. ► Prepublication history and and overactive bladder and compared these with other ► ►► For each condition, we examined trends over time additional material for this sponsored events. We hypothesised that companies in sales and dispensing of lead sponsors’ relevant paper are available online. To marketing treatments for each condition would sponsor marketed drugs, but we could not assess causal view these files, please visit related events and that target audiences would mainly links between increased prescribing and event the journal online (http://dx.doi. work in primary care, reflecting a broad patient population. attendance, as no information was publicly available http://bmjopen.bmj.com/ org/10. 1136/bmjopen- 2017- Main outcome measures Event and attendee 019027). on the identity of individual event participants. characteristics, sponsoring companies, related marketed ►► Limited detail was available on the content of Preliminary study results were treatments, cost-effectiveness ratings and dispensing sponsored events; therefore, despite a sensitive presented at the Preventing rates. Overdiagnosis Conference in search, we may have missed some relevant events Results Over the study period, we identified 1567 events Barcelona, Spain, September per condition. 2016. focusing on depression, 1375 on osteoporosis and 190 on overactive bladder (total n=3132, with 96 660 attendees). Received 6 August 2017 These events were attended by primary care doctors more Introduction
Revised 25 October 2017 often than sponsored events without a focus on these on October 1, 2021 by guest. Protected copyright. Accepted 28 November 2017 three conditions: relative risk (RR)=3.06 (95% CI 2.81 The role of pharmaceutical industry spon- to 3.32) for depression, RR=1.48 (95% CI 1.41 to 1.55) sorship of health professional education has for osteoporosis and RR=2.59 (95% CI 2.09 to 3.21) for been subject to considerable controversy. overactive bladder. Servier, which markets agomelatine There is disagreement about whether spon- and AstraZeneca (quetiapine) sponsored 51.2% and sored education is primarily promotional or 23.0% of depression events, respectively. Amgen educational. It has been described on the one and GlaxoSmithKline, which co-market denosumab, hand as ‘marketing masquerading as educa- sponsored 49.5% of osteoporosis events and Astellas and tion’1 and on the other, if accompanied by Commonwealth Serum Laboratories (CSL) (mirabegron and proper controls, as able to meet the goal of solifenacin) sponsored 80.5% of overactive bladder events. ‘needs based, relevant, accessible education Conclusions This 4-year overview of industry-sponsored that is balanced and unbiased and improves events on three overdiagnosed and overtreated conditions 2 found that primary care clinicians were often targeted, healthcare outcomes.’ For numbered affiliations see dinner was often provided and that a few companies This controversy extends to how treatment end of article. sponsored most events. In most cases, sponsors’ products outcomes are discussed and how condi- Correspondence to are not cost-effective choices for the specified condition. tions are defined. Messages in commer- Dr Barbara Mintzes; This pattern highlights the need for professional education cially sponsored education may exaggerate barbara. mintzes@sydney. edu.au to be free of commercial sponsorship. prevalence and/or attempt to medicalise
Mintzes B, et al. BMJ Open 2018;8:e019027. doi:10.1136/bmjopen-2017-019027 1 Open Access BMJ Open: first published as 10.1136/bmjopen-2017-019027 on 13 February 2018. Downloaded from aspects of ordinary life. Identified ‘marketing messages’ These data provide a unique opportunity to examine in continuing medical education (CME) for low female the link between condition-specific sponsored events and sexual desire included statements that it is ‘very common companies marketing medicines for a condition. Over and underdiagnosed’ and that ‘women may not be aware this 4-year period, 116 845 events are described, varying that they are sick or distressed.’3 Similarly, US CME in scope from a half-hour journal club in a hospital sponsored by a testosterone manufacturer supported a meeting room to several-day conferences, sometimes broader definition of hypogonadism than in listed indica- held overseas.12 tions for testosterone.4 We report here on event sponsorship with a focus on A sponsored CME campaign can reach many health three conditions highlighted in the medical literature as professionals, with potential widespread effects on prac- potentially subject to overdiagnosis and overtreatment: tice. Purdue Pharma’s launch of the opioid analgesic depression,13 osteoporosis14 and overactive bladder.15 We oxycodone in the USA included over 20 000 sponsored hypothesise that companies marketing drugs for these educational events, many of which targeted general prac- conditions are more likely to sponsor events with a focus titioners (GPs), potentially contributing to more opioid on that condition than other companies. We also hypoth- use in primary care.5 esise that these events tend to target primary care practi- These are product-specific examples of sponsored tioners who are likely to treat milder disease states than CME that received media attention and may not reflect specialists. To test these hypotheses, we compare charac- broader trends. There has been little exploration of the teristics of the events focusing on these three conditions link between sponsored CME and specific conditions with other events sponsored by companies during the prone to overdiagnosis. Overdiagnosis, the detection of 4-year study period. conditions unlikely to lead to ill health, disability or death To investigate clinical implications, we examine whether in the absence of treatment, has been characterised as a sponsors’ products were judged to be cost-effective and ‘modern epidemic’.6 7 It can lead to harm from adverse are covered under Australia’s Pharmaceutical Bene- effects of treatments from which a person is unlikely to fits Schemes (PBS). The PBS was introduced in 1948 to benefit, to psychological harm if a healthy person suffers subsidise the costs of outpatient medicines for the entire from anxiety or stigma due to disease labelling and to Australian population. The aim is to provide affordable harm to society through higher healthcare costs. There access to needed medicines. An expert committee, the is evidence of commercial influence on overdiagnosis Pharmaceutical Benefits Advisory Committee (PBAC), in a range of conditions through direct and indirect recommends listing of medicines based on cost-effective- marketing aiming to establish the need for a product.7 ness considerations that include both therapeutic gains One consequence of overdiagnosis is overtreatment, as and price. Medicines not listed on the PBS tend to have overdiagnosis expands the pool of potentially treatable very limited sales. patients beyond thresholds at which treatment has been We assess sponsorship patterns per condition in terms shown to be beneficial. The wide ranging influence of of audience, clinical versus non-clinical setting and provi- http://bmjopen.bmj.com/ industries that benefit from expanded markets has been sion of meals. We examine how often events included highlighted as a key driver.8 company-sponsored dinners as events with dinners National patterns of industry sponsorship can shed provided are often held at restaurants and represent a light on controversies concerning the role of sponsored higher value gift. For products for which there was a shift CME. From 2007 to late 2015, members of Medicines in which company held distribution rights over the study Australia, the national pharmaceutical industry trade period, we also examine timing of event sponsorship in association, were required by law to report on sponsored relation to distribution rights. events for health professionals.9 These are described by on October 1, 2021 by guest. Protected copyright. Medicines Australia as ‘educational events’ and include both accredited CME and a large range of events without Methods accreditation.10 Data sources Australia was one of the first countries to require the We downloaded 301 publicly available company reports pharmaceutical industry to publicly report financing covering the period from October 2011 to September of hospitality for health professionals. In 2007, the 2015 from the Medicines Australia website (www.medi - Australian Competition Tribunal required Medicines cinesaustralia.com.au), converted them from PDF into Australia—who at the time opposed the move—to intro- Excel files, cleaned the data and resolved discrepancies. duce mandatory disclosure of industry-sponsored events For example, we removed text from columns that should for health professionals following recommendations have contained numeric values only (eg, total cost) and, by the Australian Competition and Consumer Commis- for a small minority of events, corrected totals equal to sion (ACCC). Unlike other countries relying on industry less than reported component costs. self-regulation of drug promotion via national industry These reports include the sponsoring company, timing, associations, Australia has what could be described as a event description, venue type, number and profession quasi-regulatory system, requiring approval of self-regu- of attendees, hospitality costs and total event costs. latory standards by a public regulatory body, the ACCC.11 Coding methods are described in detail elsewhere.12 We
2 Mintzes B, et al. BMJ Open 2018;8:e019027. doi:10.1136/bmjopen-2017-019027 Open Access BMJ Open: first published as 10.1136/bmjopen-2017-019027 on 13 February 2018. Downloaded from developed a retrospective cohort of sponsored events Coding of Medicines Australia data on sponsored events based on timing of sponsorship per company over time. An initial coding scheme for industry-sponsored events A descriptive overview of the data on sponsored events included sponsoring company, location, attendee profes- has been published,12 and the dataset used for this sion, clinical focus, type of hospitality (such as whether analysis is available at http://dx.doi.org/10.4227/11/ meals or travel and accommodation were provided) and 592631edbd9d5. a set of relevant keywords to search unstructured text.12 We obtained a list of brands sold in Australia for each We designed an additional coding scheme to identify condition from the Australian Medicines Handbook16 and events focusing on the three included conditions. The manufacturers’ websites and annual dispensing data research team iteratively developed keywords based on for publicly reimbursed drugs through Australia’s PBS disease names/symptoms and drug classes and products at http://www.pbs.gov.au/info/browse/statistics#AS. sold in Australia (generic and brand names) for each For non PBS-subsidised drugs, sales volume data were condition. Keywords were used to search unstructured obtained through Quintiles IMS. text in the ‘Description of function’ column of reports. We examined volume of use using annual numbers All relevant keywords associated with one or more events of dispensed prescriptions for PBS-subsidised drugs and listed in the database were retained in the final coding numbers of units sold to retail and hospital pharmacies scheme (see online supplementary appendix tables 1 and for non PBS-subsidised drugs. 2). During coding, we concealed other variables (using Excel’s ‘Column Hide’ function) to blind the coder (SS) Selection of targeted conditions to sponsor, attendee characteristics and event descriptors. We chose depression, osteoporosis and overactive bladder as illustrative case studies of conditions for which diag- Analysis nostic thresholds and treatment have extended beyond For each included condition, we provide a detailed anal- levels at which patients are likely to benefit. We selected ysis for all companies sponsoring at least 5% of events. these conditions a priori before carrying out any analyses. We examined whether these companies market drugs to Depression screening leads to many false positives,17 18 treat the condition and PBS reimbursement status for and many patients prescribed antidepressants in primary these drugs. We present frequency tables for event and care fail to meet diagnostic criteria for major depression,19 attendee characteristics. Costs are reported in Australian a phenomenon that has been described as ‘medicalising dollars. We performed χ2 analyses to compare events per sadness’.13 In 2013, Australia had one of the highest rates condition with other sponsored events using SPSS V.22. of antidepressant use among Organisation for Economic Cooperation and Development (OECD) countries.20 Questions have also been raised about diagnostic Results criteria for osteoporosis and the role of bone densi- Over the 4-year study period, we identified 3132 events tometry in greatly expanding the treatable population, focusing on the three conditions, with 96 620 attendees. http://bmjopen.bmj.com/ primarily when used in screening of asymptomatic post- This included 1567 events with a focus on depression, menopausal women and as a diagnostic tool for women with 41 474 attendees; 1375 on osteoporosis with 33 916 with low-trauma fractures. Bone density screening is attendees and 190 on overactive bladder with 21 270 poorly predictive of clinical fractures, and a focus on attendees. As no individuals are named, we could not bone density rather than fragility fractures has led to ascertain numbers of repeat attendees. Table 1 summarises many more diagnoses.14 Further treatment expansion event characteristics. Events focusing on these conditions has occurred through lowered thresholds for ‘pre-osteo- represent 2.7% of sponsored events (n=116 845) over the porosis’ and ‘osteopenia’, which further extend disease 4-year period and 2.8% of attendees (n=3 481 750).12 on October 1, 2021 by guest. Protected copyright. labelling to populations that fail to meet established For all three conditions, the median number of event criteria for a diagnosis of osteoporosis. attendees (19 to 20) was similar to sponsored events An ‘imprecise’ symptom-based definition of over- in general.12 For all three conditions, events were held active bladder, largely linked to commercial interests, less often in a clinical setting (hospital or clinic) than has replaced urodynamically confirmed bladder insta- other sponsored events: relative risk (RR)=0.51 (95% bility.15 Tolterodine, marketed by Pharmacia, was the CI 0.50 to 0.53) for depression; RR=0.72 (95% CI 0.68 first drug approved for overactive bladder symptoms. In to 0.76) for osteoporosis; RR=0.47 (95% CI 0.43 to 2002, Pharmacia’s vice president described a threefold 0.50) for overactive bladder. Nurses were only at 24.4% expansion of the treatable population through a defini- of condition-focused events compared with 39.6% of tion of overactive bladder no longer requiring urinary total events,12 likely reflecting the less frequent hospital incontinence.21 setting. However, attendees were more likely to be Drug treatments for these three conditions have been primary care physicians (GPs or family medicine) than heavily advertised to the public in the USA, with adver- at other events: RR=3.06 (95% CI 2.81 to 3.32) for tising that relies heavily on emotional appeals, targets depression, RR=1.48 (95% CI 1.41 to 1.55) for osteo- women and tends to blur the boundaries between normal porosis, and RR=2.59 (95% CI 2.09 to 3.21) for overac- life and medical conditions requiring treatment.22 tive bladder. Depression and osteoporosis events were
Mintzes B, et al. BMJ Open 2018;8:e019027. doi:10.1136/bmjopen-2017-019027 3 Open Access BMJ Open: first published as 10.1136/bmjopen-2017-019027 on 13 February 2018. Downloaded from 548 (41) 332 (0.2%)
33
270 (0.6)
ology 30 (15.9) $A2 $A1115 ($A91–1868) $A55 ($A11–80) 21 20 (13–34) 50 (26.3) 132 (69.5) 18 (9.5) 46 (24.2) $A568 $A2012 ($A765–3370) $A85 ($A31–90) 44 (23.2) 158 (83.2) 41 (21.6) 28 (14.7) 2 (1.1) 7 (3.7) 1 (0.5) 79 (41.6) 916 (1.0)
$A2 314 319 (38) $A337 ($150–1478) $A17 ($A11–75) Endocrinology 516 (37.5) Ur Osteoporosis (n=1375)Osteoporosis 33 Overactive bladder (n=190) 19 (12–27) 921 (67.0) 638 (46.4) 531 (38.6) 359 (26.1) Rheumatology 190 (13.8) Ob/Gyn 13 (6.8) $A6 073 333 (2.1%) $A686 ($A217–2500) $A52 ($A13–119) 692 (50.3) 1298 (94.4) 512 (37.2) 485 (35.3) 69 (5.0) 77 (5.6) 58 (4.2) 97 (7.1) ession (n=1567) 472 (1.2)
$A2 441 950 (39) $A911 ($A135–1712) $A57 ($A11–77) 41 19 (12–28) 839 (53.5) 1159 (74.0) 222 (14.2) 357 (22.8) Geriatrics 55 (3.5) $A6 259 581 (2.2%) $A1941 ($A659–3264) $A104 ($A48–141) 487 (31.1) 1441 (92.0) 811 (51.7) 241 (15.4) 15 (1.0) 24 (1.5) 62 (4.0) 288 (18.4) http://bmjopen.bmj.com/ 845) Depr
723 (16.9) Psychiatry 804 (51.3)
670 (9.1)
667 (90.4)
060 (68.5) 662 (21.1) 774 (38.3) 214 (39.6) 998 (64.2) 873 (17.0) 935 (22.2) 067 (12.0) 806 (11.0) 873 (25.6)
05 on October 1, 2021 by guest. Protected copyright.
Total events (n=116 Total 18 (12–25) 80 24 44 46 Oncology 19 10 Surgery $A286 117 928 $A263 ($A153–1195) $A14 ($A10–68) 74 1 19 25 14 12 3113 (2.7) 29 ed events for the three conditions ed events for the three ovided e doctors Characteristics of sponsor
otal number of attendees (% total) 3 481 750 otal cost of events T Primary car T Median cost per event (IQR) Median cost per head (IQR) Food and drink cost (% of total cost)Median per event food and drug cost (IQR)Median per head food and drink cost (IQR) $A197 ($A107–405) $A84 862 791 (30) $A12 ($A8–20) Any food pr All-day event meals Median/event (IQR) Medical specialists Trainees Nurses Most frequent Second Clinical setting Dinner Lunch Tea Breakfast Unspecified Ob/Gyn, obstetrics and gynaecology. Event characteristics (%)
Attendees (% of events) Clinicians present (% of events) of medical specialists present Types Expenses ($A) Table 1 Table
4 Mintzes B, et al. BMJ Open 2018;8:e019027. doi:10.1136/bmjopen-2017-019027 Open Access BMJ Open: first published as 10.1136/bmjopen-2017-019027 on 13 February 2018. Downloaded from http://bmjopen.bmj.com/
Figure 1 Per cent of events sponsored by each company, in total and per condition. Companies that sponsored at least 5% of events are listed. also more likely to feature a dinner than other events: antidepressant agomelatine and AstraZeneca (23.0% of RR=1.73 (95% CI 1.64 to 1.82) for depression and events), which markets the antipsychotic quetiapine. The RR=1.33 (95% CI 1.27 to 1.38) for osteoporosis. This extended-release formulation of quetiapine (brand name on October 1, 2021 by guest. Protected copyright. trend was not seen for overactive bladder. Seroquel XR) is approved for depression treatment in The median cost per attendee was higher than for patients intolerant to other therapies or with inadequate events in general ($A14): $A104 for depression, $A52 for response. Neither agomelatine nor the depression indi- osteoporosis and $A85 for overactive bladder (table 1). cation for quetiapine are PBS subsidised. Pfizer, which A few companies sponsored most of these condi- markets five PBS-subsidised antidepressants (desvenla- tion-focused events. Figure 1 provides an overview of faxine, venlafaxine, sertraline, reboxetine, doxepin), was companies sponsoring ≥5% of events. All sell at least the next most frequent sponsor (16.0% of events). one drug for the relevant indication. Table 2 provides We examined agomelatine and quetiapine sales an overview of these drugs’ PBS funding status. We volumes over the study period. Agomelatine sales tripled, present illustrative event descriptions featuring brand from 99 625 units in 2012 to 300 103 units in 2015 (28 days names in table 3, with added details on sponsored treatment/unit). Sales of the extended-release formula- events per company in online supplementary appendix tion of quetiapine increased from 247 374 units in 2012 to table 3. 374 917 in 2015 (60 days treatment/unit). Sales of other Depression-related events AstraZeneca quetiapine formulations decreased over the Two companies sponsored >80% of depression-related same period, from 499 445 units sold in 2012 to 202 783 in events: Servier (51.2% of events), which markets the 201523 (see online supplementary appendix figure 1.1).
Mintzes B, et al. BMJ Open 2018;8:e019027. doi:10.1136/bmjopen-2017-019027 5 Open Access BMJ Open: first published as 10.1136/bmjopen-2017-019027 on 13 February 2018. Downloaded from Continued December 2014: Sanofi transfers marketing rights to Actavis 2009: co-commercialised 2009: co-commercialised by Amgen and GSK; Dec all 2015: Amgen reacquires marketing rights in Australia Quetiapine is PBS-funded for Quetiapine acute mania schizophrenia; and bipolar disorder Notes February 2001: postmenopausal osteoporosis; minimal February 2001: postmenopausal osteoporosis; trauma; cost-minimisation versus alendronate fracture December 2001— extended to corticosteroid-induced osteoporosis 2013: extended to patients aged 70+BMD March T-score≤−2.5 July 2015: restricted to severe established osteoporosis, established osteoporosis, to severe July 2015: restricted patients unable to use other drugs, without cardiovascular contraindications risks August 2016: delisted due to cardiac General schedule‡ July 2008: authority required¶ cost-minimisation versus July 2008: authority required¶ November 2008: listing extended: women aged alendronate; 70+; BMD T-score≤−3.0 November 2009: extended to men listing changed to July 2011: 3-year limit removed; authority streamlined July 2010: cost-minimisation† versus zoledronic acid July 2010: cost-minimisation† versus zoledronic authority§, postmenopausal November 2011: streamlined ≤−2.5; cost-minimisation age 70+, BMD T-score osteoporosis, versus alendronate non- acid rejected; July 2013: superiority versus zoledronic inferiority accepted General schedule‡ listings, major depressive disorder General schedule‡ listings, major depressive November 2008: cost minimisation† versus venlafaxine; no evidence of therapeutic advantage November 2011: inadequate clinical evidence to support superiority July 2013: non-inferior comparative safety and effectiveness not established November 2010: uncertainty; inappropriate comparator November 2010: uncertainty; inappropriate and 2012: superior clinical effectiveness July 2011, March safety over SSRIs not demonstrated http://bmjopen.bmj.com/ Yes No (previously No (previously subsidised) Yes Yes Yes Yes Yes No for MDD, treatment-resistant or depression anxiety disorders No PBS subsidy?(Y/N) PBAC decisions and rationale for restrictions ession, osteoporosis and overactive bladder marketed by sponsoring companies ession, osteoporosis on October 1, 2021 by guest. Protected copyright. Risedronic acid (Actonel, Actonel Ec, Risedronic Actonel Ec Combi, Combi D) Strontium (Protos) Strontium Oestradiol/norethisterone (Estalis Oestradiol/norethisterone Continuous) Zoledronic acid (Aclasta) Zoledronic Denosumab (Prolia) Venlafaxine (Efexor-XR, Altven), (Efexor-XR, Venlafaxine sertraline (Zoloft), reboxetine doxepin (Sinequan) (Edronax), Desvenlafaxine (Pristiq) Quetiapine (Seroquel XR)* Quetiapine (Seroquel Agomelatine (Valdoxan) Drug for condition (brand) PBS subsidy of drugs marketed for depr
Sanofi Servier Novartis Amgen and GSK Pfizer AstraZeneca Servier
Osteoporosis
Depression
Company Table 2 Table
6 Mintzes B, et al. BMJ Open 2018;8:e019027. doi:10.1136/bmjopen-2017-019027 Open Access BMJ Open: first published as 10.1136/bmjopen-2017-019027 on 13 February 2018. Downloaded from 742.95
Total cost Total $A4138.84 $A3750.00 $A4136.5 $A11 2014: marketed by CSL October 2014: Astellas marketing rights regains Notes Dinner, including alcoholic Dinner, and non- alcoholic beverages non alcoholic beverages Three-course dinner, dinner, Three-course non-alcoholic juice/water, beverage, alcoholic beverage Food and beverages Professionals presentProfessionals Hospitality 26 advanced trainees, hospital pharmacists, psychiatrists 35 GPs, Psychiatrists Dinner with alcoholic and 38 GPs, Endocrinologists 10 leading specialists in with an interest OAB—especially Urologists dens arra St, Venue The Sebel Resort, NSW Windsor, Kimberly Gar St Kilda East VIC GG Restaurant, 105 Y Geelong VIC 3220 The Terrace Room The Terrace (Private Dining), L'Aqua, Sydney, NSW July 2007: uncertain clinical benefit and cost-effectiveness February 2011—October NA. No request made for PBS listing NA. No request http://bmjopen.bmj.com/ red events red essive disorder; NA, not applicable; PBAC, Pharmaceutical Benefits Advisory Committee; PBS, essive disorder; No No PBS subsidy?(Y/N) PBAC decisions and rationale for restrictions depr
hours
on October 1, 2021 by guest. Protected copyright. esentation including a discussion on minute pr
hour educational content
Valdoxan-specific patient cases Valdoxan-specific Educational dinner meeting for GPs with a specialist Patient’. on ‘The Anxious Depressed presentation 1 the confidence to switch appropriate patients from patients from the confidence to switch appropriate GSK was not responsible bisphosphonates to Prolia. the educational content. Duration of for organising educational content: 2 Kerrebroeck giving educational launch presentation on giving educational launch presentation Kerrebroeck in the management BETMIGA, the new oral treatment One hour educational content. of overactive bladder.
Solifenacin (Vesicare) Mirabegron (Betmiga) Mirabegron Drug for condition (brand) 2014 mineral density; GSK, GlaxoSmithKline; MDD, major
Continued Illustrative examples of verbatim descriptions sponso
CSL and Astellas Astellas Overactive bladder Scheme; SSRI, selective serotonin reuptake inhibitor. reuptake Scheme; SSRI, selective serotonin Company XR. only Seroquel not indicated for MDD or general anxiety disorder, are quetiapine products *Immediate release to listed comparator; no higher pricing allowed. non-inferior in safety and efficacy is considered †Cost-minimisation: product ‡General schedule: no prior authority required. as authority exceed specified levels, treated if quantities and/or repeats on the prescription; authority code is required but a streamlined required, authority: no prior approval §Streamlined required. Department of Health prior to prescribing. from required telephone or written approval ¶Authority required: BMD, bone Sponsor Date Event content OAB, overactive bladder; VIC, Victoria. New South Wales; NSW, professional; health care general practitioner; GSK, GlaxoSmithKline; HCP, GP, Servier May 2012 120 Astrazeneca August GSK June 2015 HCPs with Providing presentation. HCP osteoporosis Astellas April 2014 Philip Van Educational dinner meeting. Prof Table 2 Table Table 3 Table
Mintzes B, et al. BMJ Open 2018;8:e019027. doi:10.1136/bmjopen-2017-019027 7 Open Access BMJ Open: first published as 10.1136/bmjopen-2017-019027 on 13 February 2018. Downloaded from
Figure 2 Invitation for an AstraZeneca sponsored event. http://bmjopen.bmj.com/
Seventy-nine AstraZeneca events focused on ‘the no osteoporosis events from October 2014 onwards (see anxious depressed patient’. Figure 2 is an invitation for online supplementary appendix figure 1.2). one of these events, featuring the same image that was Denosumab dispensations increased nearly sevenfold used in an advertisement for extended-release quetiapine over the study period, from 45 220 in 2012 to 309 350 that appeared in the Medical Journal of Australia. This in 2015.25 Risedronate, zoledronic acid and strontium formulation of quetiapine is also indicated for gener- dispensations all decreased (see online supplementary alised anxiety disorder. appendix figure 1.3) Of 193 events mentioning denosum- on October 1, 2021 by guest. Protected copyright. ab’s brand name, Prolia, 104 were sponsored by Amgen Osteoporosis-related events and 88 by GSK. Osteoporosis event sponsorship, similarly, was highly concentrated: Amgen and GSK, which comarket denos- Overactive bladder-related events umab, sponsored 31.3% and 18.1% of events respectively Two companies dominated sponsorship of overactive (in total, 49.4%). Novartis, which markets zoledronic bladder events: Astellas (40.5% of events), which markets acid, and oestradiol/norethisterone, a hormone therapy mirabegron and solifenacin, the latter after October 2014 approved for osteoporosis prevention in high-risk women and CSL (40.0% of events), which marketed solifenacin intolerant of other products, sponsored 19.9% of events; from February 2011 to October 2014. Neither drug is Servier, which markets strontium, sponsored 15.0%; and PBS subsidised. Astellas did not request PBS reimburse- Sanofi, which marketed risedronic acid until December ment for mirabegron. PBAC rejected solifenacin in 2007, 2014, sponsored 8.7%. Denosumab, zoledronic acid, judging benefits and cost-effectiveness to be uncertain. oestradiol/norethisterone and risedronic acid are PBS All CSL-sponsored overactive bladder events occurred subsidised; strontium was delisted in August 2016 due to while the company held distribution rights for solifenacin cardiac risks. to October 2014. Most Astellas-sponsored events were Sanofi transferred its marketing rights for risedro- held from 2014 onwards, when it obtained marketing nate to Actavis in December 2014.24 Sanofi sponsored rights (see online supplementary appendix figure 1.4).
8 Mintzes B, et al. BMJ Open 2018;8:e019027. doi:10.1136/bmjopen-2017-019027 Open Access BMJ Open: first published as 10.1136/bmjopen-2017-019027 on 13 February 2018. Downloaded from Both solifenacin and mirabegron sales increased over the to the unique Australian dataset, this is the first such data- study period (see online supplementary appendix figure driven national analysis to examine condition-specific 1.5). event sponsorship. Company reports on financing of sponsored events provided limited information on content, leaving many Discussion questions unanswered. More research is needed on the In this analysis of 3132 Australian pharmaceutical indus- messages in sponsored education, including on thresh- try-sponsored events with 96 660 attendees, focusing on olds for disease diagnosis and treatment. Additionally, as three clinical conditions prone to overdiagnosis, we found individuals were not named, we could not directly eval- a strong concentration of sponsorship among few compa- uate the link between event attendance and individual nies. Two companies sponsored over 70% of depression prescribing patterns. events; another two companies over 80% of overactive We could only examine potential contributions to bladder events. For osteoporosis, the two companies that overdiagnosis and overtreatment indirectly. We had comarket denosumab sponsored nearly 50% of events. hypothesised that events would focus on primary care, Several products marketed by key event sponsors were reflecting milder disease states. This is a hypothesised considered unacceptable for PBS reimbursement, and association only; we could not directly assess whether are associated with cost, efficacy and safety concerns that the messages in these events promote overdiagnosis or have been flagged internationally. Servier, which spon- overtreatment. However, nearly two-thirds of events, sored over half of depression-related events, sells agome- 62%, for the three conditions were attended by primary latine which is not PBS subsidised. Agomelatine is not care doctors, versus 21% of other events. The focus approved in the USA or Canada. A French independent on primary care was most pronounced for depression drug bulletin, Prescrire, characterised the drug as ‘more events: 74%. dangerous than useful’ and called for its withdrawal in The concentration of sponsorship by companies 2015.26 A Spanish bulletin, similarly, considered it ‘worse marketing products subject to safety, cost and efficacy than first-line antidepressants, up to 15-fold more expen- concerns raises questions about influences on prescribing sive and a worrying hepatic safety profile.’27 choice. This pattern is consistent with Brody and Light’s A 2012 Cochrane systematic review found that Astra- hypothesis of an ‘inverse benefit law’, in which intense Zeneca’s atypical antipsychotic quetiapine had limited marketing of drugs that may benefit a small proportion efficacy evidence for depression.28 An updated systematic of patients is harmful to public health because a broader review, published in 2015, concluded that quetiapine had patient population is targeted than is likely to benefit.35 not been shown to improve function and that method- Many of these condition-focused events included ological biases had exaggerated benefits and minimised dinner and were held in non-clinical settings such as harm.29 restaurants. Costs per person were higher than for events Like agomelatine, denosumab is on the French bulletin in general. Even small gifts, such as food and drink, http://bmjopen.bmj.com/ Prescrire’s list of 71 drugs to avoid in 2016 because of ‘a can affect behaviour.36 An analysis of US transparency disproportionate risk of adverse events’ including serious reports found that physicians who receive one or more infections due to immunosuppression, with only modest sponsored meals with a mean value of
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