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The impact of a physician detailing and sampling program for generic atorvastatin: an interrupted time… Worthington, Heather C; Cheng, Lucy; Majumdar, Sumit R; Morgan, Steven G; Raymond, Colette B; Soumerai, Stephen B; Law, Michael R Nov 25, 2017

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RESEARCH Open AccessThe impact of a physician detailing andsampling program for generic atorvastatin:an interrupted time series analysisHeather C. Worthington1,6* , Lucy Cheng1, Sumit R. Majumdar2, Steven G. Morgan3, Colette B. Raymond4,Stephen B. Soumerai5 and Michael R. Law1AbstractBackground: In 2011, Manitoba implemented a province-wide program of physician detailing and free samplingfor generic atorvastatin to increase use of this generic statin. We examined the impact of this unique combinedprogram of detailing and sampling for generic atorvastatin on the use and cost of statin medicines, marketshare of generic atorvastatin, the choice of starting statin for new users, and switching from a branded statinto generic atorvastatin.Methods: We conducted a retrospective study of Manitoba insurance claims data for all continuously enrolledpatients who filled one or more prescriptions for a statin between 2008 and 2013. Data were linked to physician-leveldata on the number of detailing visits and sample provision. We used interrupted time series analyses to assesspolicy-related changes in the use and cost of statin medicines, market share of generic atorvastatin, the choice ofstarting statin for new users, and switching from a branded statin to generic atorvastatin.Results: The detailing program reached 31% (651/2103) of physicians who prescribed a statin during the study period.Collectively, these physicians prescribed 61% of statins dispensed in the province. Free sample cards were provided to61% (394/651) of the detailed physicians. The program did not change the level or trend in the overall statin use rateand the total cost of statins or increase the number of patients switching from another branded statin to genericatorvastatin. We found the program had a small impact on atorvastatin’s market share of new prescriptions, with alevel increase of 2.6%.Conclusions: Though physician detailers were skilled at targeting high-prescribing physicians, a combined program ofdetailing visits and sample provision for generic atorvastatin did not lower overall statin costs or lead to switching frombranded statins to the generic. The preceding introduction of generic atorvastatin appeared sufficient to modifyprescribing patterns and decrease costs.Keywords: Detailing, Atorvastatin, Sampling, Generic drugsBackgroundControlling prescription drug expenditures remains atop priority for both public and private drug programs.One important cost-saving opportunity is increasingthe use of cheaper (but therapeutically interchangeable)generic alternatives [1]. In Canada, each province hasits own public drug plan and policies regarding genericdrugs. However, the use of generics is encouraged by allCanadian provincial drug plans and some private drugplans through some form of mandatory generic substi-tution rules and interchangeability provisions that allowgenerics to be dispensed instead of more expensivebrand-name alternatives [2]. As a result, generic drugsrepresented 71.5% of all the prescriptions dispensed inCanada in 2013 [3]. It is in the interest of insurers world-wide to encourage switching to generic alternatives given* Correspondence: heather.worthington@ubc.ca1Centre for Health Services and Policy Research, School of Population andPublic Health, Faculty of Medicine, The University of British Columbia,Vancouver, British Columbia, Canada6201-2206 East Mall, Vancouver, BC V6T 1Z3, CanadaFull list of author information is available at the end of the article© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link tothe Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Worthington et al. Implementation Science  (2017) 12:141 DOI 10.1186/s13012-017-0671-zthe major potential for savings, especially as the avail-ability of generic drugs continues to rise [4].One commonly used and effective method to changeprescribing is “physician detailing”—the use of face-to-face visits by sales representatives to promote the pre-scribing of particular medicines [5, 6]. Most frequently,methods are employed to increase the use of medicinesremaining under patent protection. However, many drugprograms have attempted to steer physicians toward pre-scribing the most cost-effective agent using similar tac-tics of face-to-face visits in the practice of academicdetailing, in order to improve both quality and cost ef-fectiveness of care [7].While the impact of academic detailing in isolationhas been well studied [8], there have been few rigorousstudies on the impact of providing samples on physician-prescribing behavior. The small number of publishedstudies suggests that the availability of branded samplesincreases prescribing of more expensive branded medica-tions over more cost-effective and/or preferred medica-tions [9–12]. Two observational studies suggest thatgeneric sampling programs on their own have a small orlimited impact on overall generic dispensing rates [13, 14].To our knowledge, there has only been one study pairinggeneric sampling with physician detailing that demon-strated a 1.77% increase in the overall generic dispensingrate over and above the impact of physician detailingalone [15]. We are not aware of any studies that comparea combined program of physician detailing and samplingto the status quo (no intervention).In 2011, Manitoba Health implemented an innovativeprogram aimed at increasing the use of generic atorva-statin, a cholesterol-lowering statin medicine. At thetime, atorvastatin was the top-selling drug in the world[16]. Many other drugs are also available within the statinclass (such as rosuvastatin, simvastatin, and fluvastatin)and are therapeutically equivalent [17]. This program useddetailers who visited high-prescribing physicians to pro-mote the use of generic atorvastatin, with the intent of en-couraging new patients to start on generic atorvastatinand established patients to switch to generic atorvastatinfrom rosuvastatin, which at the time remained availableonly as a more expensive branded drug. What differenti-ated this program from conventional “academic detailing”is that it included the distribution of cards that providedfree samples of generic atorvastatin to physicians. As thereare no rigorous data on the efficacy of a combined pro-gram of detailing visits and sample provision on genericdrug use, we studied the impact of the program.MethodsStudy contextIn 2011, Manitoba was the fifth-most populous provincein Canada, with a population of 1.2 million [18]. Manitobahas a provincial Pharmacare program that covers allManitobans; however, drugs are only reimbursed after apatient pays an annual deductible based on family income[19]. In this system, prescription drugs are paid for by amix of public and private coverage, as well as out-of-pocket by the patient.The province of Manitoba granted an exclusivelisting on the public formulary to the generic manufac-turer Ranbaxy for atorvastatin in June 2010 [20]. Reim-bursement of the Ranbaxy version of atorvastatin(Ran-Atorvastatin®) by the public plan began onOctober 14, 2010. In exchange for this exclusive listing,Ranbaxy initiated a program of physician detailing andfree sampling, which started in June 2011. Ranbaxy used aprivate company specializing in the promotion of medi-cines and recruited two staff members to detail physicians.These representatives promoted the use of Ran-Atorvastatin® to physicians that were high prescribers ofstatins in the province and provided electronic cards thatpatients could exchange at the pharmacy for a free 30-daysupply of Ran-Atorvastatin®. The program aimed to in-crease Ran-Atorvastatin® prescribing while decreasing pre-scribing of more expensive but therapeutically equivalentbranded atorvastatin and branded rosuvastatin. As a pri-vate firm conducted these visits, we assumed that the de-tailing methods employed were similar to those used fordetailing visits of other medicines. The intent was thatthese representatives should detail physicians every 45 to60 days, with a target to see each physician six to ninetimes per year.Data sources and study populationWe conducted a retrospective study of Manitoba insur-ance claims data for all continuously enrolled patientswho filled one or more prescriptions for a statin betweenJune 2008 and March 2013. This includes data from 2years prior to generic atorvastatin being available on theManitoba Pharmacare formulary until 21 months fol-lowing the implementation of the generic detailing andsampling program. Based on prescriber information foreach statin prescription, we linked this insurance claimsdata to physician-level information on the date of eachdetailing visit and the number of sample cards providedduring each encounter.This study used administrative data that includesindividual-level data on virtually all Manitobans con-tained in the Population Health Research Data Repository,which is housed at the Manitoba Centre for Health Policy[21]. Four population-based, administrative data sourceswere used in this analysis and linked using anonymousidentifiers: (1) prescription dispensation records fromoutpatient dispensaries through Manitoba Health’sDrug Programs Information Network, (2) ManitobaHealth Population Registry, (3) Manitoba ProviderWorthington et al. Implementation Science  (2017) 12:141 Page 2 of 8Registry (prescribers), and (4) records on the physiciandetailing visits made to each physician.Study cohortsTo study the impact of the detailing and sampling pro-gram on particular groups, we constructed two sub-cohorts of patients according to the following definitions:1. Switching: “Switchers” received a prescription for astatin after the receipt of two or more prescriptionsfor a different statin (either a different brand or abrand vs. generic) over the past year.2. Starting: “Starters” received a prescription for astatin after receiving no statin prescriptions in theprevious year [22].HypothesesWe hypothesized that the program would increase theuse of generic atorvastatin, decrease the use of other sta-tins, and decrease total costs; that the policy would havea greater impact on new starters than those switchingfrom a branded statin to generic atorvastatin; and thatthe policy would promote more switching from brandedto generic atorvastatin than from branded rosuvastatinto generic atorvastatin.Statistical analysisWe used interrupted time series analysis to study longi-tudinal changes in drug utilization and costs, the statinswhich patients start on, and rates of switching [23]. Thismethod has the distinct advantages of being methodo-logically rigorous and easily interpretable by non-technicalaudiences while also controlling for pre-existing seculartrends in the outcome. It has been successfully used bymany previous pharmaceutical policy evaluations inCanada [24–27]. Using interrupted time series analysis,we were able to estimate the change in the level and thetrend of each outcome following the start of the detailingand sampling policy. As the monthly observations werecorrelated over time, we controlled for autocorrelationusing appropriate adjustments in a generalized leastsquares model [23].Our analyses used the following measures to deter-mine the impact of the policy:Prescription drug utilization Our analysis of drugutilization focused on the number of prescriptions. Inthis analysis, we examined whether the detailing andsampling program increased the overall level of statinprescribing in the province or led to changes betweendifferent types of statins. For this analysis, we classifieddrugs into six groups: (1) branded atorvastatin, (2) gen-eric atorvastatin, (3) branded rosuvastatin, (4) genericrosuvastatin, (5) other branded statins, and (6) othergeneric statins. Branded drugs, such as Lipitor® in the caseof atorvastatin and Crestor® in the case of rosuvastatin, arereleased by the company that originally developed and mar-keted the medicine. Generics are drugs of the same mol-ecule that come to market after patent protection expires.Costs We examined the impact of the detailing programon statin cost by studying the longitudinal change inoverall statin costs within the province.Switching rate Among switchers, we examined longitu-dinal changes in the proportion of patients that switchedfrom (1) branded atorvastatin to generic atorvastatinand (2) branded rosuvastatin to generic atorvastatin.Starting medication Amongst starters, we examinedlongitudinal changes in the proportion of patients initi-ated on each of the six types of statins.ResultsProgram reachThe detailing program reached 31% (651/2103) of physi-cians who prescribed a statin during the study period.Collectively, these detailed physicians prescribed 61% ofstatins dispensed in the province. Between June 2011and February 2013, 5154 detailing visits were con-ducted, with the average physician being visited 7.9times (approximately once every 3 months). The maxi-mum number of visits to one physician was 30. Freesample cards were provided to 61% (394/651) of the de-tailed physicians. Of those physicians provided withsample cards, the median number of times sampled(visits during which sample cards were provided) was twoand the maximum number of times sampled was 14.Study cohortThere were 152,020 statin users in Manitoba with con-tinuous coverage between 2008 and 2013 included in thestudy. Of these users, 66,091 (43.4%) were new usersand 69,876 (46.0%) switched statins over the studyperiod. The age and sex of the study cohort, as well asthe new starter and switcher cohorts, are presented inTable 1.Overall statin prescribingWe observed that overall statin prescribing increasedsteadily by 486 prescriptions per month over the studyperiod (95% CI 408 to 565, p < 0.01, Fig. 1). When gen-eric atorvastatin became available, there was an almostcomplete replacement of branded atorvastatin within afew months. We observed a similar pattern for genericrosuvastatin. However, neither the release of generic ator-vastatin (level change of 732 prescriptions, 95% CI − 2223to 3686, p = 0.28, trend change of − 40 prescriptions perWorthington et al. Implementation Science  (2017) 12:141 Page 3 of 8month, 95% CI − 574 to 494, p = 0.74) nor the detailingand sampling program (level change of 785 prescriptions,95% CI − 1897 to 3467, p = 0.20, trend change of − 156prescriptions per month, 95% CI − 695 to 384, p = 0.21)had a significant impact on overall statin prescribing.Overall statin costsTotal statin costs were rising at a rate of $34,884 permonth (95% CI 18,325 to 51,443, p < 0.01) before theintroduction of generic atorvastatin (Fig. 2). When gen-eric atorvastatin was put on the Manitoba formulary,there was a significant $1,096,543 drop in cost of statins(95% CI − 1,720,604 to − 472,482, p < 0.01), though wefound no significant change in trend ($− 81,721 permonth, 95% CI − 194,527 to 31,086, p = 0.25). Wefound no further changes in the level ($307,228, 95%CI − 259,149 to 873,604, p = 0.32) or trend ($− 38,513per month, 95% CI − 152,474 to 75,449, p = 0.60) ofstatin costs after the implementation of the detailingand sampling program.SwitchersWhen generic atorvastatin was put on the Manitoba for-mulary, 37,614 patients switched from branded atorva-statin to generic atorvastatin in the 6 months following.In contrast, we found no meaningful change in thenumber of patients switching from either branded ator-vastatin or branded rosuvastatin to generic atorvastatinfollowing the start of the detailing and sampling pro-gram. This can be seen in Fig. 3.StartersPrior to the introduction of generic atorvastatin, ap-proximately 1560 patients were newly started on statinseach month. As shown in Fig. 4, the introduction ofgeneric atorvastatin did not impact the level (1.3%, 95%CI − 1.3 to 3.9%, p = 0.11) or trend (0.1% per month,95% CI − 0.4 to 0.6%, p = 0.42) of atorvastatin’s share ofnew statin prescriptions. We did find, however, that thedetailing and sampling program had a small impact onatorvastatin’s market share of new prescriptions, withan increase of 2.5% (95% CI 0.1 to 5.0%, p < 0.01).Table 1 Age and sex of statin users, and new starter and switcher cohorts of statin usersAge ≤ 44 (%) 45–54 (%) 55–64 (%) 65–74 (%) 75+ (%) All agesUsers Female 5.2 15.6 28.8 25.2 25.2 70,535Male 8.3 20.5 30.8 16.6 23.8 81,484Starter Female 8.7 21.9 32.5 15.5 21.4 30,401Male 13.2 26.7 30.8 10.3 19.0 35,690Switcher Female 3.5 14.0 29.1 26.5 26.9 31,818Male 5.7 18.7 32.2 17.8 25.6 38,058Fig. 1 Statin prescribing in Manitoba from 2008 to 2013Worthington et al. Implementation Science  (2017) 12:141 Page 4 of 8Overall, this change translates to approximately 126more new atorvastatin users in the year following theprogram than would have been expected based onexisting trends. There was no significant impact on thetrend of atorvastatin’s market share of new prescrip-tions following the detailing and sampling program(− 0.2% per month, 95% CI − 0.7 to 0.3%, p = 0.14).DiscussionAs a growing number of commonly prescribed drugslose patent protection, it is becoming increasingly im-portant to promote the use of less expensive genericmedicines. Despite being run by a commercial detailingfirm and having successfully targeted high-prescribingphysicians, we found that the use of physician detailingFig. 2 Total cost of statins in Manitoba from 2008 to 2013Fig. 3 Number of people who switched from a branded statin to generic atorvastatin from 2009 to 2013Worthington et al. Implementation Science  (2017) 12:141 Page 5 of 8and sample provision in Manitoba did not meaningfullyimpact either generic statin use or overall statin costs.Importantly, we found the program did not promoteswitching established users from branded rosuvastatin,despite this being one of the main aims of the program.Finally, while we did find an impact on the choice ofstarting statin for new users, the size of this effect wasvery small.Our results run counter to a significant body of evi-dence in support of academic detailing [7, 28–33] andmounting evidence in support of sample provision inmodifying prescribing behavior [9–11]. We proposetwo possible explanations for this discrepancy. First,mandatory generic substitution rules and interchange-ability provisions existed in Manitoba that requiredpharmacists to dispense generics in place of equivalentbrand-name alternatives [34]. This means that even if aphysician prescribes the branded drug, unless thephysician has explicitly stated that there are to be nosubstitutions, the pharmacy will dispense the genericdrug. As shown above, when generic atorvastatin be-came available on the Manitoba formulary, there wasan almost complete replacement of branded atorva-statin within a few months prior to the detailing andsampling program. These mandatory substitution poli-cies are very effective and do not seem to have any ob-vious harms [35]. Second, despite one of the program’sstated aims being to encourage switching from brandedrosuvastatin to generic atorvastatin, there is very littleevidence to suggest that this was an achievable goal.There have been many studies indicating physician’sreluctance to change an effective treatment [36]. Therefore,if a patient’s cholesterol was being well managed onbranded rosuvastatin, a physician was unlikely to switchthem to a different drug despite evidence of similar efficacy.The comparatively small impact on the choice of startingdrug may have been influenced by either detailing on thepart of rosuvastatin’s manufacturer or by the knowledgephysicians may have had about rosuvastatin’s pending pa-tent expiration. The data available only allowed us to evalu-ate the reach, fidelity, and dose of the program, but wewere unable to evaluate these contextual factors that mayhave shaped how the intervention functioned [37].While this study was designed to exploit the naturalexperiment created by the implementation of the policy,there are several limitations to our work. As our studyused administrative health data, we could not examinedetailed clinical data that might be obtained throughmedical records. Similarly, we had limited measures re-garding the appropriateness of prescribing, patient satis-faction, side effects, low-density lipoprotein levels, andhealth outcomes for individuals who were started on onestatin versus another or were switched. However, muchof the available clinical evidence suggests that thesedrugs have similar efficacy [38]. As the generic detailingand sampling program in Manitoba was only conductedfor atorvastatin, our results may not be directly applic-able to other medication classes or clinical areas. How-ever, given the widespread prescribing of these medicines,we believe our results are likely indicative of what wouldoccur with a similar program for other popularmedication classes.Fig. 4 Percent market share of new statin prescriptions in Manitoba from 2009 to 2013Worthington et al. Implementation Science  (2017) 12:141 Page 6 of 8ConclusionsIn a strictly regulated environment that includes genericsubstitution, simply releasing a low-cost generic drugwill influence new starters on the drug to be prescribedthe generic. Switches on the other hand tend to be morerefractory, and even well-designed and evidence-basedprograms to accelerate these pharmaceutical policieshave no room to further increase starts and do not affectswitching.AcknowledgementsThe authors acknowledge the Manitoba Centre for Health Policy, ManitobaHealth, and Seniors and Active Living, for use of data contained in thePopulation Health Research Data Repository under project # (HIPC 2012/13 #53).The results and conclusions are those of the authors and no official endorsementby the Manitoba Centre for Health Policy, Manitoba Health, Seniors and ActiveLiving, or other data providers is intended or should be inferred.FundingThis research was funded by an operating grant from the Canadian Institutesof Health Research (MOP-286790, “The Impact of a Physician Detailing andSampling Program for Generic Atorvastatin,” Principal Investigator: Michael Law).Michael Law received salary support through a New Investigator Award fromthe Canadian Institutes of Health Research and a Scholar Award from theMichael Smith Foundation for Health Research. The results and conclusions arethose of the authors and no official endorsement by the Canadian Institutes ofHealth Research or others is intended or should be inferred.Availability of data and materialsData for this study were obtained from the Manitoba Centre for HealthPolicy, Manitoba Health, and Seniors and Active Living for use of datacontained in the Population Health Research Data Repository under project# (HIPC 2012/13 #53). These data are available, but restrictions apply to theavailability of these data, which were used under license for the currentstudy and so are not publicly available. Data are however available from theauthors upon reasonable request and with permission of the ManitobaCentre for Health Policy, Manitoba Health, and Seniors and Active Living.Prior presentationsGeneric Atorvastatin: The impact of physician detailing and sampling inManitoba, Canadian Association of Health Services & Policy Research,28/05/15, Montreal, Canada.Authors’ contributionsMRL, SRM, SGM, and CBR conceived of and designed the study. All authorscontributed to the acquisition, analysis, or interpretation of data. HCW andMRL drafted the manuscript. All authors critically revised the manuscript forimportant intellectual content. LC and HCW contributed to the statisticalanalyses. MRL obtained funding for and supervised the study. All authorsapproved the manuscript for submission.Ethics approval and consent to participateThe University of British Columbia Behaviour Research Ethics Board (H13-00983)approved this study. As this study used administrative data, consent was notrequired.Consent for publicationNot applicable.Competing interestsMichael Law has consulted for Health Canada on unrelated pharmaceuticalpolicy topics. All other authors declare no competing interests.Publisher’s NoteSpringer Nature remains neutral with regard to jurisdictional claims inpublished maps and institutional affiliations.Author details1Centre for Health Services and Policy Research, School of Population andPublic Health, Faculty of Medicine, The University of British Columbia,Vancouver, British Columbia, Canada. 2Department of Medicine, University ofAlberta, Edmonton, Alberta, Canada. 3School of Population and PublicHealth, Faculty of Medicine, The University of British Columbia, Vancouver,British Columbia, Canada. 4Manitoba Centre for Health Policy, Max RadyCollege of Medicine, Rady Faculty of Health Sciences, University of Manitoba,Winnipeg, Manitoba, Canada. 5Department of Population Medicine, HarvardMedical School, Boston, MA, USA. 6201-2206 East Mall, Vancouver, BC V6T1Z3, Canada.Received: 8 February 2017 Accepted: 13 November 2017References1. Kesselheim AS, et al. 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Am J Cardiol. 2008;102(12):1654–62.•  We accept pre-submission inquiries •  Our selector tool helps you to find the most relevant journal•  We provide round the clock customer support •  Convenient online submission•  Thorough peer review•  Inclusion in PubMed and all major indexing services •  Maximum visibility for your researchSubmit your manuscript atwww.biomedcentral.com/submitSubmit your next manuscript to BioMed Central and we will help you at every step:Worthington et al. Implementation Science  (2017) 12:141 Page 8 of 8


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