Marketing Pharmaceutical Science for Prestige and Profit PREPRINT

By David J Elpern, M.D.

As a dermatologist, I have observed the profusion of research articles on psoriasis over the past two decades.  A graph of these from PubMed illustrates the five-fold increase in references since the first biologic, infliximab, was approved by the FDA in 1998. (Figure 1) This increase in scientific studies has coincided with a profusion of new therapies for psoriasis and may reflect the pharmaceutical industry’s interest in developing and promoting costly new treatments for this common chronic skin disorder. 

With this in mind, a recent article in the New England Journal of Medicine, “Trial of Roflumilast Cream for Chronic Plaque Psoriasis” piqued my interest.¹ It is a phase 2B study of a new topical phosphodiesterase type 4 (PDE-4) inhibitor that compares the active agent to placebo. The lengthy author disclosure section at the end of the article for the eight principal dermatologist authors runs over 90 small font lines. At the end of this is the provocative sentence; “We thank…Julia R. Gage, of Gage Medical Writing, for medical writing assistance with an earlier version of the manuscript.”

I was curious to learn how conflicted the authors of this paper were.  Of the 15 main authors, six are U.S. dermatologists not primarily employed by the study’s sponsor, two are Canadian dermatologists and there are seven others who are employed by Arcutis, the sponsor.  An additional 22 investigators participated in the ARQ-151 201 Study: 14 are U.S. dermatologists and eight are Canadians. Thus, of the total 37 individuals who contributed to this study, 20 are U.S. dermatologists, 10 are Canadian dermatologist researchers and the remaining 7 are drug company employees (including two MBA’s).

OpenPayments collects and publishes information about financial relations between the U.S. health care industry and providers.² This is made possible by The Sunshine Act that requires medical product manufacturers to disclose to the Centers for Medicare and Medicaid Services (CMS) any payments or other transfers of value made to physicians or teaching hospitals.³  

Table 1 is the composite of the disbursements from 2013 to 2019 to the six U.S. author/researchers of the Roflumilast study for the NEJM article from OpenPayments. Table 2 depicts the payments to the 14 ARQ Study researchers. Many of the six primary authors are Key Opinion Leaders (KOL’s) who are also paid well to speak at CME conferences and who edit the throwaway journals dermatologists receive.

The six U.S. dermatologists who are primary authors collectively were paid over $42,000,000 by industry in general and research monies.  The 14 U.S. Study investigators netted $76,469,560.  Thus, the 20 US dermatologists were reimbursed $118,470,000 by the pharmaceutical industry for their work as researchers and promoters of drugs. This does not take into account the monies industry paid the 10 Canadian researchers. The pharmaceutical industry clearly has deep pockets for physician investigators.

Of the 15 senior authors of this paper, seven are Arcutis employees. These include the Chief Medical Officer, two company vice-presidents, the Chief Technical Officer and two MBAs.  Three of the paper’s senior authors are on the five member Arcutis “Scientific Advisory” board. The fact that these three authors are the study sponsor’s Senior Advisors is a COI that could not be deduced from even a close reading of the article.  Of the eight primary dermatologist authors (six U.S. and two Canadian), all receive funding from multiple companies. (Table 3).  Their reported disclosures range from 3 to 41 companies with a mean of 19 and a median of 16.  In addition, as Table 3 illustrates, their output of scientific papers as retrieved from PubMed is profuse.  It is hard to understand how they could be so productive until one understands the shadowy practices of Pharma’s publication planning process.⁵

Articles such as this may be the products of the publication planning strategy on the part of industry.^5,6 Drug company scientists identify a promising molecule and research commences. If Phase 1 and 2 studies appear propitious, the company’s executives may bring on board a medical education and communications company (MECC) to commence publication planning.  They have experts in marketing, scientific writing, and publication planning whose strategy it is to improve the odds that the article will be accepted by a high-impact-factor, peer-reviewed journal.  A medical writing team often produces the first drafts and then high-profile clinical scientists come on board.  As KOL’s their names are recognizable to readers and carry the seal of respected academic institutions. Their names are prominently placed in the author list; but they often enter the final writing at a late stage.⁶ Considering how many articles some KOL’s publish annually, it’s hard to conceive how they manage to produce them without help; yet the ghost writers are barely acknowledged.  The end result is a professional-appearing product designed to provide an industry message.

When reading articles on pharmacotherapy like this one, it is important for readers to recognize that chronic diseases such as psoriasis are lucrative markets and that some physicians do very well working for industry.  It is easy to get distracted with the slick hype from this inconvenient truth especially when the research is given the imprimatur of the New England Journal of Medicine whose 2019 impact factor of 74.699 was the highest of all general medical journals.

As physicians, we must ask ourselves how we feel about research such as that presented in the Roflumilast study.¹ Does it pass the smell test?

References:

1. Lebwohl MG, et al. Trial of Roflumilast Cream for Chronic Plaque Psoriasis. N Engl J Med. 2020 Jul 16;383(3):229-239.

2. OpenPayments. https://openpaymentsdata.cms.gov/

3. Richardson E. The Physician Payments Sunshine Act. Health Affairs. October 2014

4. Arcutis Biotherapeutics. https://arcutis.com/

5. Fugh-Berman A, Dodgson. Ethical considerations of publication planning in the pharmaceutical industry. Open Med. 2008;2(4) Free Full Text

6. Sismondo S, Ghost-Managed Medicine: Big Pharma’ Invisible Hand. Mattering Press 2018.  Chapter 3. Ghosts in the Machine: Publication Planning 10

Acknowledgement: I would like to thank Dr. Richard Ratzan for his close reading and constructive editing and comments.

Figure
PubMed References on Psoriasis 1978 – 2020

Table 1

Monies generated by U.S. Authors as calculated.
Found on CMS Open Payment Site.

Roflumilast Study U.S. Primary Authors

	Gen Payments	All Research Payments	Total
1	398,000	7,005,000	7,403,000
2	1,959,000	1,686,000	3,645,000
3	3,907,000	7,944,000	11,851,000
4	474,000	6,528,000	7,002,000
5	47,000	10,056,000	10,056,000
6	884,000	1,252,000	2,136,000
Totals	7,669,000	34,471,000	42,093,000
Mean	1,281,000	5,745,000	7,015,000
Median	1,422,000	5,551,000	7,203,000

Table 2

Roflumilast Study U.S. ARQ-151 201 Study Investigators

	General Payments	All Research Payments	Total
1	252,000	2,682,000	2,934,000
2	172,000	4,761,000	4,933,000
3	125,000	5,140,000	5,265,000
4	4820	1,263,000	1,268,000
5	5,346	5,397,000	5,402,000
6	9,642	4,741,000	4,751,000
7	44,000	9,973,000	10,007,000
8	656,000	568,000	1,224,000
9	7667	4,404,000	4,412,000
10	76,000	181,000	257,000
11	697,000	11,151,000	11,848,000
12	4044	1,960,000	1,964,044
13	4516	2,796,000	2,801,516
14	939,000	18,464,000	19,403,000
Total	2,997,035	73,481,000	76,469,560
Mean	214,100	5,249,000	5,462,000
Median	60,000	4,572,000	4,642,000

Table 3

Companies Disclosed and Articles Published (Six U.S. Authors and 2 Canadians)

Author	Companies Dis- closed	Papers Written/Co-authored	Active in past 20 years
1	41	454	1999 – Present
2	40	261	1999 – Present
3	9	121	2007 – Present
4	20	120	2014 – Present
5	13	221	2007 – Present
6	5	256	1999 – Present
7	3	37	1999 – Present
8	21	168	1999 – Present
Totals	152	1638
Mean	19	205
Median	16	195