an examination of u.s. pharmaceutical marketing: are top · 2017. 5. 4. · confidential: for...
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An Examination of U.S. Pharmaceutical Marketing: Are Top-
Promoted Drugs Less Effective and Less Innovative than Top-Selling and Top- Prescribed Drugs?
Journal: BMJ
Manuscript ID BMJ.2016.036713
Article Type: Analysis
BMJ Journal: BMJ
Date Submitted by the Author: 22-Nov-2016
Complete List of Authors: Greenway, Tyler; Yale University Ross, Joseph; Yale University School of Medicine, Internal Medicine
Keywords: pharmaceutical, industry promotion, drug value
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An Examination of U.S. Pharmaceutical Marketing:
Are Top-Promoted Drugs Less Effective and Less Innovative
than Top-Selling and Top- Prescribed Drugs?
Tyler Greenway, BA1; Joseph S. Ross, MD, MHS2
1 Yale University School of Medicine, New Haven, Connecticut; 2 Section of General Internal
Medicine and the Robert Wood Johnson Foundation Clinical Scholars Program, Yale
University School of Medicine; Department of Health Policy and Management, Yale
University School of Public Health; and Center for Outcomes Research and Evaluation,
Yale–New Haven Hospital, all New Haven, Connecticut.
Correspondence: Joseph S. Ross, MD, MHS, Section of General Internal Medicine, Yale
University School of Medicine, PO Box 208093, New Haven, CT 06520-8093
Manuscript Word Count: 2250
Tables: 2 References: 17
Appendix Tables: 2
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KEY MESSAGES
• Between August 2013 and December 2014, $3.53 billion was paid to 681,432
physicians in the United States by 1,630 pharmaceutical companies to promote
numerous drug products; untold amounts were paid to physicians outside of the
United States.
• Top-promoted drugs differ significantly from top-selling and top-prescribed drugs
and are less likely to represent the ideal “high-value” drug that is effective, safe,
affordable, novel, and represents a genuine advance in treating a disease.
• Clinicians should question the value of drugs being most heavily promoted by
pharmaceutical manufacturers before prescribing medications for their patients.
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Throughout the world, the pharmaceutical industry employs a variety of techniques
to promote its products to physicians and other clinicians, including gifts and free food,
advertisements, and detailing by company representatives. While manufacturers might
argue that drug promotion supports physician education, which in turn leads to more
informed prescribing, prior studies have demonstrated that greater contact with
pharmaceutical sales representatives is associated with an increased likelihood of
prescribing brand name medications when cheaper, therapeutic alternatives exist.1 2 More
recent studies have demonstrated that payments from pharmaceutical companies are
associated with a greater likelihood of prescribing promoted drugs.3-5
In the United States, physicians have extensive financial relationships with the
pharmaceutical industry.6 7 Beginning in August 2013, as part of the 2010 U.S. Affordable
Care Act, the Physician Payments Sunshine Act required that all payments to physicians of
$10 or more or $100 in aggregate be systematically disclosed by pharmaceutical companies
to the U.S. government and made publicly available. This legislation led to the creation of
the Open Payments Database, which archives all industry payments to individual
physicians and teaching hospitals.8
Early analyses of the Open Payments database make clear that numerous small gifts
can often add up to large sums of money,9 10 potentially creating powerful incentives for
physicians to prescribe selected medications. In this analysis, our objective was to
characterize the “value” of drugs being most aggressively promoted to physicians in order
to better understand implications of pharmaceutical promotion for patient care.
ASSESSING DRUGS’ VALUE
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We identified the 25 top-promoted drugs of 2013-2014 using information obtained
from the Open Payments Explorer created by the non-profit investigative journalism group
ProPublica, which makes the Open Payments database more easily accessible to
consumers.11 Specifically, we identified the 25 drugs associated with the largest sum of
payments that were made to physicians and teaching hospitals from August 2013 to
December 2014, including all direct and indirect payments such as speaker fees for
education lectures, consulting fees, and honoraria, as well as payments in-kind, such as the
value of food and gifts. However, we excluded research payments and the value of royalties
and licensing fees, which are typically not promotional.
Next, we approximated drugs’ “value”. In theory, drug value to society (as opposed
to the drugs’ manufacturer) depends on the relative effectiveness and safety of the drug, its
priority among available therapeutic alternatives, its level of innovation as an advance in
therapy, the prevalence of the disease for which it is indicated, the disease’s attributable
morbidity and mortality, and the cost to patients and insurers. The ideal “high-value” drug
would be an effective, safe, novel, recommended as first-line therapy for common diseases
of significant morbidity and mortality, and affordable. Therefore, we sought to estimate
drug value by using five common-sense proxy measures, which we selected to be readily
intuitive and reproducible by practicing physicians in order to allow comparisons among
available drug products.
1) Innovation. We determined whether the drug represents a new class of treatment
(first-in-class), an advance in a previously existing class (advance-in-class), or an
addition to a previously existing class with no discernable advancement of therapy
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(addition-to-class), following a schematic established by the U.S. Food and Drug
Administration (FDA).12 Drugs representing new mechanistic pathways in treating
indicated diseases were considered first-in-class. The advance-in-class designation
was awarded to drugs that did not establish new classes but received “priority
review” status from the FDA, available only to therapies that represent a clinically
meaningful advance over previously existing treatments. Drugs that met none of
these criteria were considered addition-to-class.
2) Effectiveness and Safety. As a measure of relative effectiveness and safety, we used
the ratings systems of Prescrire International, a French pharmaceutical industry
watchdog that evaluates the evidence supporting pharmaceuticals and classifies
them using ratings such as “offers an advantage”, “possibly helpful”, or “nothing
new”.13 Prescrire employs a robust evaluation process, whereby 10 or more
reviewers, physicians, pharmacists, nurses, and dentists with no conflicts of interest
who have undergone 2-3 years of specialized training on drug evaluation, review
each drug evaluation for quality control. For drugs for which Prescrire ratings were
not available, assessments were extrapolated based on Prescrire statements in
materials and guidelines. For instance, many commonly used drugs such as
levothyroxine, lisinopril, and metoprolol are recommended in Prescrire guidelines
but have no official Prescrire rating.
3) Generic Availability. As a proxy measure of affordability for patients, we used
information available within the FDA’s Drugs@FDA online database to determine
whether the drug was generically manufactured in the U.S., or whether there was a
therapeutic equivalent within the drug’s class with comparable clinical utility
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available in the U.S. Because generic drugs are available as low-cost but equally
effective and safe substitutes for brand-name prescription drugs, this metric offers
insight into drugs’ fiscal value.
4) Clinical Utility. As a measure of clinical utility for highly prevalent diseases, we
determined whether each drug is on the World Health Organization (WHO) list of
Essential Medicines for 2015. This list includes the drug products that are essential
to any basic, fully-functional healthcare system, and offers a simple metric that
reflects both the utility of the drug and the relative prevalence of the disease for
which it’s indicated. Drugs containing multiple active ingredients, including asthma
combinations and HIV drugs, were considered to be an Essential Medicine if any of
its active ingredients were listed by the WHO.
5) First-line Status. As a measure of priority among available therapeutic alternatives,
we determined whether the drug was recommended as a first-line treatment for its
respective disease using guidelines accessed through the National Guidelines
Clearing House.14 For example, metformin was categorized as first-line for the
treatment of type 2 diabetes mellitus by the American Association of Clinical
Endocrinologists guideline, while exenatide, sitagliptin, canagliflozin, and liraglutide
were not since their use is recommended only after other therapies have been
initiated. If relevant specialty society guidelines could not be identified, UpToDate
was used to determine first-line status.
In order to characterize and contrast the “value” of the 25 top-promoted drugs, we
also rated the “value” of the top 25 drugs by 2014 U.S. sales, as well as the top 25 most
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prescribed drugs in the U.S. during 2013, both of which were identified using information
obtained from IMSHealth (2014 data for top prescribed drugs was not available).15 A
complete list of all included drugs, and how each was categorized for each of the 5
measures of value, is available in the Appendix. We used chi-square tests to compare value
across these three categories of top 25 drugs, calculated using JMP 10.0 (SAS Institute,
Cary, NC).
ASSESSMENT OF HIGHLY PROMOTED PRODUCTS
Table 1 lists the top 25 drugs in terms of promotion, sales, and prescribing volume.
Among the 25 top-promoted, we included 24 drugs; one product, HP Acthar (used
diagnostically in testing adrenocortical function) was excluded from our analysis due to its
non-therapeutic use. Among the 25 top-selling, we included 25 drugs; one product, Prevnar
(anti-pneumococcal vaccine), was excluded due to its non-therapeutic use, whereas two
other products, Neulasta (pegfilgrastin) and Neupogen (filgrastin), were listed as one but
considered as distinct products. Among the 25 top-prescribed, we included all 25 drugs
without exclusions. Among the 24 top-promoted drugs, 4 (17%) were also identified
among top-selling drugs, while none were identified among top-prescribed drugs.
Innovation Among top-promoted drugs, 8 of 24 (33%) were categorized as first-in-class or
advance-in-class, in contrast to 18 of 25 (72%) top-selling drugs and 13 of 25 (52%) top-
prescribed drugs (Table 2). Top-promoted drugs were significantly less likely to be
innovative when compared with top-selling drugs (Relative Risk [RR]=0.46, 95%
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Confidence Interval [CI], 0.25-0.86; p=0.01), but not when compared with top-prescribed
drugs (RR=0.64, 95% CI, 0.32-1.26; p=0.20).
Effectiveness and Safety Among 21 top-promoted drugs for which Prescrire ratings were
available, 4 (19%) were rated as “possibly helpful” or “offers an advantage,” while 13
(62%) were rated as “nothing new” and 4 (19%) as “not acceptable”. In contrast, 11 of 25
(44%) top-selling drugs and 19 of 25 (76%) top-prescribed drugs were rated as “offers an
advantage” or “possibly helpful”. While top-promoted drugs were not less likely to be rated
favorably by Prescrire when compared with top-selling drugs (RR=0.43, 95% CI, 0.16-1.16;
p=0.10), they were significantly less likely when compared with top-prescribed drugs
(RR=0.25, 95% CI, 0.10-0.62; p=0.003).
Generic Availability Among top-promoted drugs, 15 of 24 (63%) were available as a
generic or had a comparable, generically manufactured treatment option available within
its class, as did 8 of 25 (32%) top-selling drugs and 25 of 25 (100%) top-prescribed drugs.
Top-promoted drugs were significantly more likely to have a generic option available when
compared with top-selling drugs (RR=1.95, 95% CI, 1.01-3.74; p=0.04), and less likely
when compared with top-prescribed drugs (RR=0.62, 95% CI, 0.46-0.85; p=0.003).
Clinical Utility Among top-promoted drugs, 1 of 24 (4%) was identified by the WHO as an
Essential Medicine, in contrast to 9 of 25 (35%) top-selling drugs and 14 of 25 (56%) top-
prescribed drugs. Top-promoted drugs were significantly less likely to be identified by the
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WHO as an Essential Medicine when compared with both top-selling drugs (RR=0.12, 95%
CI, 0.02-0.85; p=0.03) and top-prescribed drugs (RR=0.07, 95% CI, 0.01-0.52; p=0.009).
First-Line Status Among top-promoted drugs, 8 of 24 (33%) are considered first-line
treatments, in contrast to 15 of 25 (60%) top-selling drugs and 20 of 25 (80%) top-
prescribed drugs. While top-promoted drugs were not less likely to be considered first-line
treatments when compared with top-selling drugs (RR=0.56, 95% CI, 0.29-0.85; p=0.08),
they were significantly less likely when compared with top-prescribed drugs (RR=0.42,
95% CI, 0.23-0.76; p=0.004).
UNDERSTANDING PROMOTION
When compared to top-selling and top-prescribed drugs, the most aggressively
promoted drugs in the U.S. are less innovative, rated less favorably by Prescrire, and are
less likely to be recognized as first-line treatments by national guidelines, included on the
WHO Essential Medicines list, and available as a generic. While not all comparisons were
statistically significant, likely because of the limited sample sizes of 25 or fewer drugs in
each of the three categories, for the most part, the directionality and magnitude of the
effect estimated suggested that top-selling and top-prescribed drugs, not top-promoted
drugs, were more likely to represent the ideal “high-value” drug that is effective, safe,
affordable, novel, and represents a genuine advance in treating a disease.
PROMOTING HIGHER-VALUE MEDICINES
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Our analysis suggests that top-promoted drugs may be less effective, less novel, less
clinically useful, less affordable, and possibly even less safe (safety is considered in
Prescrire evaluations), raising concerns about the purpose of pharmaceutical promotion
and its influence on patient care. What can be done to foster the promotion of higher-value
medicines at the expense of lower-value ones? Alternatively, might we only expect
pharmaceutical companies to invest in the promotion of lower-value drugs? For instance, if
a genuinely innovative treatment becomes available that significantly advances patient
care, such as sofosbuvir (among the top-selling drugs), would we not expect this
information to spread rapidly amongst clinicians, perhaps through peer-reviewed
publications and scientific meeting presentations, requiring little active promotion on the
part of pharmaceutical companies? Conversely, if a “me-too” drug enters the market as an
addition-to-class with generic alternatives and minimal benefit over previous treatments,
such as rasagiline (among the top-promoted drugs), would we not expect robust promotion
is needed to facilitate the drug’s use?
Our findings suggest that pharmaceutical promotion should be met with healthy
skepticism. Clinicians may consider taking steps to limit their exposure to industry
promotion, including detailing by company representatives as well as sponsored
educational events.16 Clinicians may also consider deliberately engaging with “academic
detailing” programs, educational outreach by pharmacists, nurses and physicians that
provides noncommercial, evidence-based recommendations about medication choices.17
Finally, efforts are needed to better evaluate drugs’ value, ensuring that this information is
readily available at the point of care, informing clinical decision-making and promoting use
of higher-value medicines.
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LIMITATIONS AND SUMMARY
There are important limitations of our analysis. First, there may be other
considerations when selecting a medication, including patient experience of treatment,
prior therapies used, cost-effectiveness, and out-of-pocket costs or health plan costs.
Second, determining whether a drug has a comparable generic therapeutic option within
its class may depend on clinical context. For example, apixiban can often be replaced by
warfarin, but this may not be appropriate for patients who have contraindications to
warfarin use. Third, our list of top-promoted drugs accounted only for payments to U.S.
physicians and teaching hospitals from August 2013 to December 2014 and did not include
other promotional efforts, such as advertising to physicians, direct-to-consumer
advertising and disease awareness efforts coordinated with patient advocacy
organizations, pharmaceutical detailing to physician offices or efforts to raise product
awareness at professional and scientific meetings where transfers of value are not
exchanged, such as a meal or gift, or continuing medical education through third parties.
Finally, because data on payments to physicians from pharmaceutical manufacturers are
only available in the U.S. from this relatively recent time period, our results may not be
generalizable to earlier pharmaceutical promotion efforts in the U.S., or those outside the
U.S. However, we expect patterns of promotion to be similar, even if coverage and
reimbursement policies differ. To better understand non-U.S. promotion efforts,
requirements to publicly disclose payments to physicians from pharmaceutical
manufacturers should be considered.
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In summary, top-selling and top-prescribed drugs, not top-promoted drugs, were
more likely to represent the ideal “high-value” drug that is effective, safe, affordable, novel,
and represents a genuine advance in treating a disease. Physicians should question the
value of drugs being most heavily promoted by pharmaceutical manufacturers before
prescribing medications for their patients.
Acknowledgements
The authors would like to acknowledge William Fleischman, MD, Clinical Assistant
Professor, Department of Emergency Medicine, Yale School of Medicine, for his assistance
in checking the accuracy of the Open Payments program data.
Author Contributions: Mr. Greenway and Dr. Ross had full access to all of the data in the
study and take responsibility for the integrity of the data and the accuracy of the data
analysis. Both authors contributed to study concept and design; analysis and interpretation
of data, as well as the drafting and critical revision of manuscript; Mr. Greenway was
responsible for acquisition of data and statistical analysis, while Dr. Ross provided study
supervision.
Funding/support and role of the sponsor: This project was not supported by any external
grants or funds.
Potential Conflicts of interest: We have read and understood the BMJ Group policy on
declaration of interests and Dr. Ross declares the following interests: receiving research
support through Yale University from Medtronic, Inc. and Johnson and Johnson to develop
methods of clinical trial data sharing, from the Food and Drug Administration (FDA) to
develop methods for post-market surveillance of medical devices, from the Blue Cross Blue
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Shield Association (BCBSA) to better understand medical technology evidence generation,
from the Centers of Medicare and Medicaid Services (CMS) to develop and maintain
performance measures that are used for public reporting.
Ethical Approval: Because this project did not involve human subjects, it was exempted
from ethics approval from the Yale University School of Medicine Human Research
Protection Program.
Data sharing: Requests for statistical code and the dataset can be made to the
corresponding author at [email protected]. The dataset will be made available via a
publicly accessible repository on publication, at the Dryad Digital Repository
(datadryad.org).
Transparency: The supervising author (JSR) affirms that this manuscript is an honest,
accurate, and transparent account of the study being reported; that no important aspects of
the study have been omitted; and that any discrepancies from the study as planned (and, if
relevant, registered) have been explained.
License: The Corresponding Author has the right to grant on behalf of all authors and does
grant on behalf of all authors, a worldwide license to the Publishers and its licensees in
perpetuity, in all forms, formats and media (whether known now or created in the future),
to i) publish, reproduce, distribute, display and store the Contribution, ii) translate the
Contribution into other languages, create adaptations, reprints, include within collections
and create summaries, extracts and/or, abstracts of the Contribution, iii) create any other
derivative work(s) based on the Contribution, iv) to exploit all subsidiary rights in the
Contribution, v) the inclusion of electronic links from the Contribution to third party
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material where-ever it may be located; and, vi) licence any third party to do any or all of the
above.
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Table 1: List of top-promoted drugs of 2013-2014, top-selling drugs of 2014, and top-
prescribed drugs of 2013.
Top-Promoted Top-Selling Top-Prescribed
Eliquis (apixaban) Humira (adalimumab) acetaminophen/
hydrocodone
Bydureon (exenatide) Sovaldi (sofosbuvir) levothyroxine
Invokana (canagliflozin) Remicade (infliximab) lisinopril
Xarelto (rivaroxaban) Rituxan (rituximab) metoprolol
Brilinta (ticagrelor) Enbrel (etanercept) simvastatin
Victoza (liraglutide) Lantus (insulin glargine) amlodipine
Latuda (lurasidone) Avastin (bevacizumab) metformin
Brintellix (vortioxetine) Herceptin (trastuzumab) omeprazole
Humira (adalimumab) Advair (fluticasone,
salmeterol) atorvastatin
Aubagio (teriflunomide) Crestor (rosuvastatin) albuterol
Abilify Maintena
(aripiprazole extended
release)
Neulasta (pegfilgrastim) amoxicillin
Copaxone (glatiramer) Neupogen (filgrastim) hydrochlorothiazide
Symbicort (budesonide,
formoterol) Lyrica (pregabalin) alprazolam
Pradaxa (dabigatran) Abilify (aripiprazole) azithromycin
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Notes: Top-promoted drugs of 2014 were identified from ProPublica’s Open Payments
Explorer, whereas both the top-selling drugs of 2014 and the top-prescribed drugs of 2013
were identified using information obtained from IMS.
* Excluded because of non-therapeutic use.
Botox (onabotulinum toxin
type A) Revlimid (lenalidomide) fluticasone
Abilify (aripiprazole) Gleevec (imatinib mesylate) furosemide
Samsca (tolvaptan) Prevnar (Pneumococcal 13-
valent Conjugate Vaccine)* gabapentin
Belviq (lorcaserin) Copaxone (glatiramer) sertraline
Subsys (fentanyl) Zetia (ezetimibe) zolpidem
HP Acthar (repository
corticotropin)* Januvia (sitagliptin) tramadol
Xeljanz (tofacitinib citrate) Symbicort (budesonide,
formoterol) citalopram
Azilect (rasagiline) Nexium (esomeprazole) prednisone
Seroquel XR (quetiapine
fumarate)
Atripla (efavirenz,
emtricitabine, tenofovir) acetaminophen/oxycodone
Tecfidera (dimethyl
fumarate)
Truvada (emtricitabine,
tenofovir disoproxil
fumarate)
ibuprofen
Levemir (Insulin detemir) Avonex (interferon beta 1a) pravastatin
Celebrex (celecoxib)
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Table 2: Characteristics of drug ‘value’ for top-promoted drugs of 2013-2014, top-selling
drugs of 2014, and top-prescribed drugs of 2013.
Characteristics of Drugs’ ‘Value’
Top-
Promoted, No.
(%) (n=24)
Top-Selling,
No. (%)
(n=25)
Top-
Prescribed,
No. (%)
(n=25)
Innovation Status: "First-in-Class"
or "Advance in Class" 8 (33) 18 (72) 13 (52)
Prescrire Rating: "Offers an
Advantage" or "Possibly Helpful" 4 (19)* 11 (44) 19 (76)
Generic Equivalent Available in U.S. 15 (62) 8 (32) 25 (100)
Presence on WHO Essential
Medicines List 1 (4) 9 (36) 14 (56)
Guideline Designation as a First-
Line Treatment 8 (33) 15 (60) 20 (80)
Notes: WHO=World Health Organization.
* Prescrire ratings not available for 3 top-promoted drugs because of their recent approval
status: Brintellix (vortioxetine), Latuda (lurasidone), and Xeljanz (tofacitinib citrate).
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APPENDIX
Appendix Table 1: List of top-promoted drugs of 2013-2014, top-selling drugs of 2014,
and top-prescribed drugs of 2013, including drug characterization by innovation status,
Prescrire rating, U.S. generic drug availability, WHO essential medicines listing, and U.S.
guideline designation as a first-line treatment.
Drug
Innovation
Status
Prescrire
Rating*
Generic
Availability
in U.S.†
WHO
Essential
Medicine
Listing
First-Line
Treatment
Top-Promoted Drugs of 2013-2014
Eliquis
(apixaban)
advance-in-
class
nothing
new yes; WCG no yes
Bydureon
(exenatide)
addition-to-
class
possibly
helpful yes; WCG no no
Invokana
(canagliflozin) first-in-class
not
acceptable yes; WCG no no
Xarelto
(rivaroxaban)
addition-to-
class
nothing
new yes; WCG no yes
Brilinta
(ticagrelor)
addition-to-
class
nothing
new yes; WCG no no
Victoza
(liraglutide)
addition-to-
class
nothing
new yes; WCG no no
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Latuda
(lurasidone)
addition-to-
class missing yes; WCG no no
Brintellix
(vortioxetine)
addition-to-
class missing yes; WCG no no
Humira
(adalimumab)
addition-to-
class
possibly
helpful no no no
Aubagio
(teriflunomide)
addition-to-
class
not
acceptable no no no
Abilify
Maintena
(aripiprazole
extended
release)
addition-to-
class
nothing
new yes; WCG no no
Copaxone
(glatiramer) first-in-class
nothing
new no no yes
Symbicort
(budesonide,
formoterol)
addition-to-
class
not
acceptable no yes no
Pradaxa
(dabigatran)
advance-in-
class
possibly
helpful yes; WCG no yes
Botox
(onabotulinum first-in-class
offers an
advantage no no no
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toxin type A)
Abilify
(aripiprazole) first-in-class
nothing
new yes; TE no yes
Samsca
(tolvaptan)
addition-to-
class
nothing
new no no yes
Belviq
(lorcaserin) first-in-class
not
acceptable no no no
Subsys
(fentanyl)
addition-to-
class
nothing
new yes; WCG no no
Xeljanz
(tofacitinib
citrate)
addition-to-
class missing no no no
Azilect
(rasagiline)
addition-to-
class
nothing
new yes; TE no yes
Seroquel XR
(quetiapine
fumarate)
addition-to-
class
nothing
new yes; WCG no no
Tecfidera
(dimethyl
fumarate)
first-in-class nothing
new no no no
Levemir
(Insulin
addition-to-
class
nothing
new yes; WCG no yes
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detemir)
Top-Selling Drugs of 2014
Humira
(adalimumab)
addition-to-
class
possibly
helpful no no no
Sovaldi
(sofosbuvir)
advance-in-
class
offers an
advantage no yes yes
Remicade
(infliximab)
First-in-
class
offers an
advantage no no no
Rituxan
(rituximab)
First-in-
class
possibly
helpful no yes yes
Enbrel
(etanercept)
advance-in-
class
offers an
advantage no no no
Lantus (insulin
glargine)
addition-to-
class
possibly
helpful yes; WCG no yes
Avastin
(bevacizumab)
First-in-
class
not
acceptable no yes yes
Herceptin
(trastuzumab)
First-in-
class
offers an
advantage no yes yes
Advair
(fluticasone,
salmeterol)
addition-to-
class
not
acceptable no no no
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Crestor
(rosuvastatin)
addition-to-
class
nothing
new yes; WCG no yes
Neulasta
(pegfilgrastim)
addition-to-
class
possibly
helpful no no no
Neupogen
(filgrastim) first-in-class
judgment
reserved no yes yes
Lyrica
(pregabalin)
advance-in-
class
possibly
helpful yes no no
Abilify
(aripiprazole)
First-in-
class
nothing
new yes; TE no yes
Revlimid
(lenalidomide)
advance-in-
class
nothing
new no no yes
Gleevec
(imatinib
mesylate)
First-in-
class
offers an
advantage no yes yes
Copaxone
(glatiramer)
First-in-
class
nothing
new no no yes
Zetia
(ezetimibe)
First-in-
class
nothing
new yes; WCG no no
Januvia
(sitagliptin)
First-in-
class
nothing
new yes; WCG no no
Symbicort addition-to- not no yes no
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(budesonide,
formoterol)
class acceptable
Nexium
(esomeprazole)
addition-to-
class
nothing
new yes; TE no yes
Atripla
(efavirenz,
emtricitabine,
tenofovir)
advance-in-
class
nothing
new no yes yes
Truvada
(emtricitabine,
tenofovir
disoproxil
fumarate)
advance-in-
class
judgment
reserved no yes yes
Avonex
(interferon beta
1a)
advance-in-
class
offers an
advantage no no yes
Celebrex
(celecoxib)
First-in-
class
nothing
new yes; TE no no
Top-Prescribed Drugs of 2013
acetaminophen
/hydrocodone
addition-to-
class
possibly
helpful‡ yes; TE no yes
levothyroxine first-in-class offers an yes; TE yes yes
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advantage‡
lisinopril addition-to-
class
offers an
advantage‡ yes; TE no yes
metoprolol advance-in-
class
offers an
advantage‡ yes; TE yes yes
simvastatin addition-to-
class
offers an
advantage yes; TE yes yes
amlodipine addition-to-
class
possibly
helpful yes; TE yes yes
metformin advance-in-
class
offers an
advantage yes; TE yes yes
omeprazole first-in-class offers an
advantage yes; TE yes yes
atorvastatin advance-in-
class
nothing
new‡ yes; TE no yes
albuterol advance-in-
class
offers an
advantage‡ yes; TE yes yes
amoxicillin advance-in-
class
offers an
advantage yes; TE yes yes
hydrochlorothia
zide
advance-in-
class
offers an
advantage‡ yes; TE yes yes
alprazolam addition-to- nothing yes; TE no no
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class new‡
azithromycin advance-in-
class
offers an
advantage‡ yes; TE yes yes
fluticasone addition-to-
class
offers an
advantage‡ yes; TE no yes
furosemide first-in-class offers an
advantage‡ yes; TE yes yes
gabapentin advance-in-
class
possibly
helpful yes; TE no no
sertraline addition-to-
class
nothing
new yes; TE no yes
zolpidem addition-to-
class
nothing
new yes; TE no no
tramadol addition-to-
class
nothing
new yes; TE no no
citalopram addition-to-
class
nothing
new yes; TE no yes
prednisone advance-in-
class
offers an
advantage‡ yes; TE yes yes
acetaminophen
/oxycodone
addition-to-
class
possibly
helpful‡ yes; TE yes yes
ibuprofen advance-in- offers an yes; TE yes yes
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class advantage‡
pravastatin addition-to-
class
offers an
advantage yes; TE no yes
Notes: WCG=Within-class generic drug available; TE=FDA-approved therapeutically
equivalent generic drug available.
* Complete list of Prescrire Ratings include “Bravo”, “A Real Advance”, “Offers an
Advantage”, “Possibly Helpful”, “Nothing New”, “Judgment Reserved”, and “Not Acceptable”.
† Generic drug availability within the U.S. included any FDA-approved therapeutically
equivalent or within-class generic drug available.
‡ Indicates that Prescrire Rating was extrapolated from Prescrire guidelines.
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Appendix Table 2: Drugs designated as a first-line treatment in guidelines referenced by
the U.S. National Guidelines Clearinghouse (available at: http://www.guideline.gov/).
Drug Example of First-Line
Use Condition
Professional Society /
Organization Responsible for
Guideline and Link
Abilify (aripiprazole) schizophrenia American Psychiatry Association
http://psychiatryonline.org/pb/
assets/raw/sitewide/practice_g
uidelines/guidelines/schizophre
nia.pdf
acetaminophen/hydrocodon
e
Acute outpatient pain
control
American Society of
Anesthesiologists
https://www.guideline.gov/cont
ent.aspx?id=35259
acetaminophen/oxycodone Acute outpatient pain
control
American Society of
Anesthesiologists
https://www.guideline.gov/cont
ent.aspx?id=35259
albuterol acute asthma National Institutes of Health
http://www.nhlbi.nih.gov/files/
docs/guidelines/07_sec3_comp4
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amoxicillin various infections American Academy of Family
Physicians
http://pediatrics.aappublication
s.org/content/131/3/e964.full
atorvastatin hyperlipidemia American College of Cardiology
https://www.guideline.gov/cont
ent.aspx?id=48337
Atripla (efavirenz,
emtricitabine, tenofovir)
HIV/AIDS National Institutes of Health
http://aidsinfo.nih.gov/contentfi
les/lvguidelines/AA_Tables.pdf
Avastin (bevacizumab) metastatic colorectal
cancer
National Comprehensive Cancer
Network https://www.tri-
kobe.org/nccn/guideline/lung/e
nglish/non_small.pdf
Avonex (interferon beta 1a) relapsing-remitting
multiple sclerosis
Up-to-date
http://www.uptodate.com/cont
ents/treatment-of-relapsing-
remitting-multiple-sclerosis-in-
adults
Azilect (rasagiline) early Parkinson's
disease
American Academy of Neurology
http://www.neurology.org/cont
ent/66/7/983.full
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azithromycin various infections Centers for Disease Control and
Prevention
http://www.cdc.gov/mmwr/pre
view/mmwrhtml/rr5912a1.htm
citalopram Major Depressive
Disorder
American Psychiatric
Association
https://psychiatryonline.org/pb
/assets/raw/sitewide/practice_
guidelines/guidelines/mdd.pdf
Copaxone (glatiramer) relapsing-remitting
multiple sclerosis
Up-to-date
http://www.uptodate.com/cont
ents/treatment-of-relapsing-
remitting-multiple-sclerosis-in-
adults
Crestor (rosuvastatin) hyperlipidemia American College of Cardiology
https://www.guideline.gov/cont
ent.aspx?id=48337
Eliquis (apixaban) stroke prevention American College of Cardiology
http://content.onlinejacc.org/ar
ticle.aspx?articleid=1854230
fluticasone chronic asthma control National Institutes of Health
http://www.nhlbi.nih.gov/files/
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docs/guidelines/07_sec3_comp4
furosemide cardiogenic pulmonary
edema
American College of Cardiology
http://content.onlinejacc.org/ar
ticle.aspx?articleid=1695825&_g
a=1.121790795.1365833619.14
58091505
Gleevec (imatinib mesylate) CML National Comprehensive Cancer
Network
http://williams.medicine.wisc.ed
u/cml.pdf
Herceptin (trastuzumab) HER2 positive breast
cancer
American Society of Clinical
Oncology
http://jco.ascopubs.org/content
/32/19/2078.long
hydrochlorothiazide essential hypertension American College of
Cardiologists
http://jama.jamanetwork.com/a
rticle.aspx?articleid=1791497
ibuprofin anti-inflammatory,
analgesic, anti-pyretic
American College of
Rheumatology
http://www.rheumatology.org/
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Portals/0/Files/Gout_Part_2_AC
R-12.pdf
Lantus (insulin glargine) diabetes mellitus American Association of Clinical
Endocrinologists
https://www.aace.com/files/dm
-guidelines-ccp.pdf
Levemir (insulin detemir) diabetes mellitus American Association of Clinical
Endocrinologists
https://www.aace.com/files/dm
-guidelines-ccp.pdf
levothyroxine hypothyroidism American Association of Clinical
Endocrinologists
https://www.aace.com/files/hy
pothyroidism_guidelines.pdf
lisinopril heart failure American College of Cardiology
http://content.onlinejacc.org/ar
ticle.aspx?articleid=1695825&_g
a=1.121790795.1365833619.14
58091505
metformin Type II diabetes American Association of Clinical
Endocrinologists
https://www.aace.com/files/dm
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-guidelines-ccp.pdf
metoprolol atrial fibrillation American College of Cardiology
http://content.onlinejacc.org/ar
ticle.aspx?articleid=1854230
Neupogen (filgrastim) febrile neutropenia
prevention
Infectious Diseases Society of
America
http://www.idsociety.org/uploa
dedFiles/IDSA/Guidelines-
Patient_Care/PDF_Library/FN.p
df
omeprazole GERD American College of
Gastroenterologists
http://gi.org/guideline/diagnosi
s-and-managemen-of-
gastroesophageal-reflux-
disease/
Pradaxa (dabigatran) stroke prevention American College of Cardiology
http://content.onlinejacc.org/ar
ticle.aspx?articleid=1854230
pravastatin hyperlipidemia American College of Cardiology
https://www.guideline.gov/cont
ent.aspx?id=48337
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prednisone inflammatory
conditions (crohn's,
allergies)
American College of
Gastroenterology
http://gi.org/guideline/manage
ment-of-crohn’s-disease-in-
adults/
Revlimid (lenalidomide) multiple myeloma National Cancer Institute
http://www.cancer.gov/types/
myeloma/hp/myeloma-
treatment-pdq#link/_61_toc
Rituxan (rituximab) Non-hodgkin’s
lymphoma
National Comprehensive Cancer
Network
http://www.jnccn.org/content/
9/5/484.full.pdf
Samsca (tolvaptan) SIADH, severe
hyponatremia
UpToDate
http://www.uptodate.com/cont
ents/treatment-of-
hyponatremia-syndrome-of-
inappropriate-antidiuretic-
hormone-secretion-siadh-and-
reset-
osmostat?source=search_result&
search=SIADH&selectedTitle=2
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%7E150
sertraline Major Depressive
Disorder
American Psychiatric
Association
https://psychiatryonline.org/pb
/assets/raw/sitewide/practice_
guidelines/guidelines/mdd.pdf
simvastatin hyperlipidemia American College of Cardiology
https://www.guideline.gov/cont
ent.aspx?id=48337
Sovaldi (sofosbuvir) HCV Infectious Diseases Society of
America
http://hcvguidelines.org/full-
report/initial-treatment-hcv-
infection
Truvada (emtricitabine,
tenofovir disoproxil
fumarate)
HIV/AIDs National Institutes of Health
http://aidsinfo.nih.gov/contentfi
les/lvguidelines/AA_Tables.pdf
Xarelto (rivaroxiban) stroke prevention American College of Cardiology
http://content.onlinejacc.org/ar
ticle.aspx?articleid=1854230
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