Author’s Response to My BMJ Letter
Below is the complete text of Joppi’s response to my letter to the BMJ, which I wrote in response to their article entitled Disappointing Biotech. Note that a subscription is required to read the published version of my letter. I’m not going to get into a back and forth with them in the blog, because it’s my blog and readers cannot be assured that I’m giving them a fair hearing. However, I will respond to a couple of their inflammatory comments. First, I declared no competing interests, because I made it clear in my letter that I worked for Lilly when discussing teripratide, and I also make it clear with the name of my consulting firm that I work in the interests of the pharmaceutical industry generally. A competing interest declaration is intended to declare an interest in a specific company whose product is discussed, thus revealing an otherwise hidden bias on the part of the author. I never hide my pro-pharma bias. Therefore, I had no competing interests to declare. That Joppi et al declare their “bias on the side of patients” implies that mine is not. That was unfair of them. Indeed, although I support the industry, readers of these pages will readily determine that I am also quick to criticize industry practices that I believe do not ultimately serve the interests of patients. I have no doubt that Joppi and I disagree completely on which practices qualify.
FJC
Biotech: less innovation than expected 2 November 2005
Roberta Joppi,
Visiting scientist
“Mario Negri” Institute for Pharmacological Research, 20157 Milan, via Eritrea 62,
Vittorio Bertele’, and Silvio Garattini
Send response to journal:
Re: Biotech: less innovation than expected
Readers will be grateful to Fredric J Cohen for providing a balanced view (on line Rapid response of October 18 and BMJ 2005; 331:1025) on the topic we dealt with so unfairly (BMJ 2005; 331: 895-897). As President of Pharma Growth Strategies(http://www.pharmagrowth.com/index.html), with no declared competing interest he is in an ideal position to give an independent opinion, while admittedly we have to declare our bias on the side of patients.
With regard to the issues that disappoint our independent reader, however, we should like to make the following points:
A. According to European legislation, biotechnological products are those medicinal products which are developed by recombinant DNA technology, by controlled expression of genes coding for biologically active proteins in prokaryotes and eukaryotes including transformed mammalian cells, and by hybridoma and monoclonal antibody methods (1). The list of the products obtained by biotechnological methods that we evaluated was downloaded from the EMEA web site.
B. Although the cost of biotech products may not surprise some, it is clear to everyone that these drugs are more expensive than traditional ones. This cannot be justified solely by their development or production costs, since advertising still uses up double the resources devoted to research. Real innovation should reach the market with no such marketing effort and cost less or at most not much more.
C. The level of innovation was evaluated in relation to the clinical advantages for patients. We therefore classified biotech products as follows: Innovative: products with a better benefit/risk profile in that they offer new therapies for diseases without any effective treatment or have proved more effective or safer than existing drugs, or are active in patients resistant to available treatments. Safer: copies of products already available but produced through a DNA recombinant technique, which may offer better efficacy thanks to the lack of antibody formation or better safety because of the lack of viral contamination. Convenient: products making for better compliance, the clinical implications of which are not established yet (i.e. combined vaccines, most insulins). Me-too: analogues of products already available for which there are no proven advantages, including substances tested for superiority against placebo or for non-inferiority against an active comparator.
D. As a recombinant parathyroid hormone, teriparatide could well have been classified among the “safer substances”, but it was developed and indicated for osteoporosis (2) which is already covered by treatments with which it has not been compared. What is the true advantage for patients?
E. In the absence of any solid basis for challenging our methodological criticisms about biotech drug development it hardly seems justified to descend to insults! Dr Cohen implies that our interest lies in “more government regulation of drug innovation” but, as physicians and scientists in an independent research institute, we would like to see more clinically-oriented drug innovation.
F. Placebo-controlled trials should only be done when no proven prophylactic or therapeutic method exists and in any case the experimental treatment should be given on top of the best available care. We thoroughly agree that it is difficult to find a balance between the urgent need for drugs for patients with rare diseases while guaranteeing their quality, efficacy and safety and, when necessary and possible, making comparisons with existing drugs. Unquestionably, less stringent criteria are acceptable for orphan drugs than for drugs for more common diseases, particularly in view of the often very small numbers of patients. However, even when only a few patients are available at least a phase II study should be done, comparing the new treatment with the best available care, to establish the clinical benefit. As regards the endpoints of trials for rare diseases, like any other, information must be sought and provided on the impact of new treatments on the quality and duration of life. In the absence of documented clinical benefit biotech innovation is fruitless and therefore useless. In the interest of patients regulatory authorities need to be more demanding and rigorous in assessing and approving drugs for the market. In agreement with a general tendency for all products approved in the EU (3), we are still convinced that biotech products provide less innovation than expected.
References
1.Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency. Available on the web: http://pharmacos.eudra.org/F2/review/doc/final_publ/Reg_ 2004_726_20040430_EN.pdf
2. Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY, Hodsman AB, Eriksen EF, Ish-Shalom S, Genant HK, Wang O, Mitlak BH. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 2001; 344:1434- 1441
3. Motola D, De Ponti F, Rossi P, Martini N, Montanaro N. Therapeutic innovation in the European Union: analysis of the drugs approved by the EMEA between 1995 and 2003. Br J Clin Pharmacol 2005, 59: 475–478
Competing interests: we are on the side of patients
