A few months ago, I co-authored with Dr. Joel Lexchin an article in the British Medical Journal showing that only about 10 percent of new drug products fit the industry’s claim to develop clinically superior drugs to make patients healthier.1 About 90 percent of the time, companies use patent protection from normal price competition for monopoly pricing to develop minor variations rather than serious innovations. This constitutes a hidden business model they do not discuss.
Responses from leaders of the industry reflect the institutional corruption of facts, figures, and accounts, an important part of institutional corruption that would be good to develop further. In particular, the heads of first the British and now the European pharmaceutical trade associations, who use staff and paid journalists and science writers to manufacture a large portion of the articles in the general and science press, published on the BMJ website “facts” about how much they spend on research that are not supported by independent sources. Joel and I have just published the following response.2 Besides the mythic size of investments in research and development, the most important point concerns the lack of testing and caution about the serious side effects of new drugs. About 1 in every 5 new drugs (and 1 in 3 biologicals) cause enough serious harm to result in regulators adding their most severe warning or in being withdrawn from patient use altogether.3
Public and professional trust in the pharmaceutical industry is low, and the responses here show why. A recent study of doctors’ (dis)trust of the pharmaceutical industry funded by the Edmond J. Safra Center for Ethics at Harvard University found that they trust even well-designed trials less if sponsored by the industry.4 Stephen Whitehead, one of the respondents and the Chief Executive for the Association of the British Pharmaceutical Industry, wrote as if our data-based analysis was just a one-sided polemic and therefore he did not challenge our facts, while he offered one of his own: companies invest one third of sales in R&D. We challenged him to verify such a staggeringly high amount, but he has not done so. Instead, he wrote to discredit our “lack of understanding” and reported the industry invested one third of profits, a much smaller amount. Another tall tale cut down to size. He cited the ONS 2010 Business Enterprise Research and Development Report for exact figure of 34.3%.
Once again, we cannot trust Mr. Whitehead to check his facts. That Report contains no such figure that we can find, and in reply to an inquiry, Mr. Jim Nicholls, an officer at the Office of National Statistics wrote to say that “Unfortunately, we do not collect/publish sales or profit figures…” So even the cut-down claim of R&D investment has no basis in the ONS R&D report. We then searched the ABPI (the pharmaceutical trade association that Mr. Whitehead runs) for the missing figures on sales and profits but found none. We called, and a nice lady said someone would call back, but no one has. We emailed too, but no reply. Who knows what trustworthy, verified facts would show to be the pharmaceutical industry’s investment in R&D?
Now a more nuanced and thoughtful response has come from a senior team from the European Federation of Pharmaceutical Industries and Associations, led by Richard Bergström, but there are more inaccuracies. We thank Richard Bergström for his comments but we also take issue with much of what he has to say. First, we need to be clear that the ending of the Norwegian “medical need clause” in 1996 had nothing to do with predictions about the future value of new drugs being “unfeasible.” The Norwegian model was abandoned because Norway harmonized its drug regulatory system with that of the European Union and the EU that did not have a medical need clause.
Second, we reject the claim that predictions are not possible. While occasionally some drugs prove to be more valuable than initially thought,5 in general most new drugs provide little to no new therapeutic value. As documented in our article, an independent detailed assessment of the postmarket value of all new products (and new indications for existing products) over the last decade found only 76 out of 991 (7.7%) new products and indications offered any significant therapeutic gain.6 Mr. Bergström continues the industry myth that equates innovation with a new molecular entity (NME), when most are not therapeutic advances.
Third, if as Mr. Bergström says, new drugs cannot be adequately evaluated until they are in clinical use in the real world, why then do drug companies spend hundreds of millions of dollars promoting the early adoption of these new products rather than waiting to see how valuable they actually are? Why do drug companies persist in running clinical trials on highly selective patient groups rather than testing them in a more real world environment?7
Finally, many drug candidates “fail to survive” clinical trial testing because companies withdraw them for economic reasons (43%) rather than for reasons of efficacy (31%) and safety (21%).8 Even then, most clinical trial results do not show that the products being tested are outright failures but yield mixed results that lead companies to discontinue their development. The word “failure” is part of pharmaceutical mythology and should be replaced by the more accurate word, "withdrawal.”
1. Light D, Lexchin J. Pharmaceutical R&D - what do we get for all that money? BMJ 2012;344:e4348
2. Lexchin J, Light D. R.e. Pharmaceutical research and development: what do we get for all that money? In: BMJ blog; 2012 (15 Nov).
3. Lexchin J. New drugs and safety: what happened to new active substances approved in Canada between 1995 and 2010? Archives of Internal Medicine 2012 (Oct 8):E1-E2.
4. Kesselheim A, Robertson C, Myers J, et al. A randomized study of how physicians interpret research funding disclosures. New England Journal of Medicine 2012; 367:1119-27.
5. Yasuda S, Woosley R. The clinical value of FDA class C drugs approved from 1981 to 1988. Clinical Pharmacology and Therapeutics 1992; 52:577-82.
6. Prescrire Editorial Staff. New drugs and indications in 2011. France is better focused on patients’ interests after the Mediator scandal, but stagnation elsewhere. Prescrire International 2012; 21:106-10.
7. Van Spall H, Toren A, Kiss A, Fowler R. Eligibility criteria of randomized controlled trials published in high-impact general medical journals: a systematic sampling review. JAMA 2007; 297:1233-40.
8. DiMasi JA. Success rates for new drugs entering clinical testing in the United States. Clinical Pharmacology & Therapeutics 1995; 58:1-14.