an examination of u.s. pharmaceutical marketing: are top · 2017. 5. 4. · confidential: for...

Confidential: For Review O

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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

https://mc.manuscriptcentral.com/bmj

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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

([email protected])

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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4. Fleischman W, Agrawal S, King M, et al. Association between payments from

manufacturers of pharmaceuticals to physicians and regional prescribing: cross

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6. Campbell EG, Gruen RL, Mountford J, et al. A national survey of physician-industry

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7. Ross JS, Lackner JE, Lurie P, et al. Pharmaceutical company payments to physicians: early

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8. Centers for Medicare and Medicaid Services. Open Payments. Available at

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9. Ornstein C, Sagara E, Jones RG. What We’ve Learned From Four Years of Diving Into

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into-dollars-for-docs. Last Accessed May 6, 2016.

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payments/. Last Accessed November 20, 2016.

12. Lanthier M, Miller KL, Nardinelli C, et al. An improved approach to measuring drug

innovation finds steady rates of first-in-class pharmaceuticals, 1987-2011. Health

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13. Prescrire International. Prescrire in English. Available at

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14. Agency for Healthcare Research and Quality, U.S. Department of Health and Human

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of-2015-and-outlook-to-2020. Last Accessed November 20, 2016.

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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


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


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


omeprazole first-in-class offers an


atorvastatin advance-in-

class

nothing

new‡ yes; TE no yes

albuterol advance-in-

class

offers an


amoxicillin advance-in-

class

offers an


hydrochlorothia

zide

advance-in-

class

offers an


alprazolam addition-to- nothing yes; TE no no

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class new‡

azithromycin advance-in-

class

offers an


fluticasone addition-to-

class

offers an

advantage‡ yes; TE no yes

furosemide first-in-class offers an


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


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


ent.aspx?id=35259

albuterol acute asthma National Institutes of Health

http://www.nhlbi.nih.gov/files/

docs/guidelines/07_sec3_comp4

.pdf

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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


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


ents/treatment-of-relapsing-

remitting-multiple-sclerosis-in-

adults

Crestor (rosuvastatin) hyperlipidemia American College of Cardiology


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

.pdf

furosemide cardiogenic pulmonary

edema

American College of Cardiology


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


-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


ticle.aspx?articleid=1695825&_g

a=1.121790795.1365833619.14

58091505

metformin Type II diabetes American Association of Clinical

Endocrinologists


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-guidelines-ccp.pdf

metoprolol atrial fibrillation American College of Cardiology



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



pravastatin hyperlipidemia American College of Cardiology


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


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


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



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an examination of u.s. pharmaceutical marketing: are top · 2017. 5. 4. · confidential: for...

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