Table 1. What is the agreement called?
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Most pharmaceutical companies place a high priority on reducing their costs to offset pressure on profit margins. They also
struggle to accelerate the development of profitable new drugs: Based on drug sale statistics, pharmaceutical companies lose
substantial revenue each day a new drug is delayed from reaching the market. Drug company profit pressures flow downhill to suppliers such as clinical research investigators. Few if any investigative
sites are highly profitable. Well-run sites achieve pretax profit margins of 10 to 15 percent. Most sites lose money and eventually
leave the business.
Pharmaceutical companies and investigative sites therefore share a common interest in reducing costs and accelerating clinical
trials. This paper discusses activities in the United States, Canada, Britain, and Germany to achieve these objectives through
the development and use of model clinical trial agreements (CTAs).
A model CTA should accelerate the average clinical trial by at least two weeks and potentially much more. This is a modest
goal, since it takes sponsors an average of 35 days to negotiate CTAs with community-based sites and site management organizations,
and 96 days with academic centers.1 These numbers understate the problem for several reasons:
- Studies are not complete until the slowest site finishes.
- Sponsors cannot negotiate CTAs with all the sites simultaneously.
- The large proportion of investigators who sign CTAs without any negotiation skews the community-based average low.
- Given that multiple studies are required for new drug applications, the time lost in negotiating the CTAs along the critical
path multiplies the problem.
Table 2. What is the subject called?
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Sponsors and sites have very different perspectives on CTAs. Sponsors see one agreement, the one their legal departments drafted.
Their contract negotiators are usually contract specialists and have access to attorneys. For each study, they negotiate agreements
with many sites and know what issues the sites raise most frequently. Although this paper will not discuss budgets, sponsors
generally have access to third-party cost data that is not affordable for most sites. In contrast, sites see many agreements, one for each sponsor. Sites seldom, if ever, write the agreements. They have no visibility
on what concerns the other sites. Negotiators at smaller sites are usually generalists, without affordable access to contract
specialists or attorneys. Because sites compete for the business, most do not have the luxury of negotiating any but the most
critical terms in an agreement. The very real threat exists that other sites will sign the agreement quickly, and with few
or no changes.
Based on the analysis of 10 Phase II and Phase III CTAs, the agreements display a startling lack of consistency in both form
and substance. Form varies with respect to terminology (Tables 1 and 2), phrasing, and organization. Substance varies with
the content (and presence) of the terms and the level of detail in which they are presented (Tables 3 and 4).
Table 3. Definition variation example: "CRF"
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International initiatives Outside of the United States, at least three groups have developing model CTAs or guidance documents: The Association of the
British Pharmaceutical Industry (ABPI), the University of Toronto and affiliated hospitals, and the Federation of German Hospitals
(Deutsche Krankenhausgesellschaft or DKG). In the United Kingdom, the ABPI Pharmaceutical Industry Competitiveness Task Force Clinical Research Working Group negotiated
a model CTA with the Department of Health, acting on behalf of the National Health Service. Industry representatives included
AstraZeneca, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, Pharmacia (now part of Pfizer), and Wyeth. Remarkably, all of
these companies were able to agree on a single text. The resulting documents, "Model Clinical Trial Agreement" and "Model
CTA Guidance," were published in January 2003 and are available from http://www.abpi.org.uk. The model CTA has been adopted almost universally in the United Kingdom. Various parties have made various modifications,
but preserved the agreement's principles. The model CTA is currently being revised for compliance to the European Union's
Clinical Trials Directive.
In Canada, the University of Toronto and affiliated hospitals formed the Toronto Academic Health Science Council (TAHSC) Clinical
Study Agreements Working Group (CSAWG), which developed a set of publication rights principles. The document, "Protection
for Intellectual Freedom and Publication Rights," is posted at http://www.library.utoronto.ca/medicine/medUT/publication_rights.pdf .
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