Supporting Legislation for Independent Post-Marketing (Phase IV) Comparative Evaluation of Pharmaceuticals

[摘要]

The American Public Health Association,

Recalling that between 1990 and 2000 nearly 1,000 new prescription drugs including more than 300 new molecular entities were introduced into the U.S. market;^1,2 and

Noting that the regulatory requirement for a demonstration of efficacy of a new drug proposed for approval demands only a showing that the drug is more effective than a control^3,4 — e.g., a placebo — not necessarily a showing of effectiveness superior to or even comparable to, that of existing effective drugs;⁵ and

Seeing that, nevertheless, newer pharmaceuticals are heavily marketed as superior to products available previously;^6,7 and

Cognizant of the brief duration and the limited scope of clinical trials – usually only 500-3,000 subjects, with volunteernbias in the participant base, with few youth, elderly, pregnant women, and patients with complicating chronic conditions;^8-10 and

Observing that the pre-approval research to assess the safety and efficacy of a new pharmaceutical product is commonly designed, carried out, and reported by, or under the direction of, the company that wants to bring the product to market;¹¹ and

Aware that the current infrastructure for new-drug research permits biased design of clinical trial protocols (for example, a drug study protocol may compare the new drug with a somewhat elevated dosage of a standard drug, resulting in more dropouts and a greater proportion of adverse events in the standard drug group), and that the current paucity of independent study sponsorship permits conflicts of interest and suppression of negative or non-significant findings;^12-15 and 

Noting that, although major professional efforts to gain pertinent reforms began more than 30 years ago¹⁶ and although there are numerous industry-sponsored studies to compare the effectiveness and safety of available treatment options, relatively few comparative studies are done by investigators whose salary and research funding are independent of the pharmaceutical industry and of public-private partnerships;^17,18 and

Concerned that, although modest funding (e.g., by the National Institutes of Health) produces some federally sponsored independent studies of drug effectiveness and safety in community-based populations, absence of a mandate for routine assessment of new drugs in terms of long-term drug effectiveness, long-term safety, and patient satisfaction means not only that the field remains under-funded but also that when independent study findings are available they fail to receive exposure comparable to industry sponsored findings;¹⁹ and

Realizing, further, that, in efforts to contain rapidly increasing expenditures for prescription drugs,²⁰ state Medicaid programs and private health insurers have been establishing drug formularies, which can constrain prescribers’ options and limit affordability of certain medications by beneficiaries; and

Noting that a paucity of reliable data on comparative effectiveness and safety of therapeutic alternatives tends to frustrate due consideration of these factors when formularies are designed, and 

Cognizant of the differing national standards for drug safety reflected in government recall or manufacturers’ voluntary withdrawal of products in European countries and Canada while those drugs continue to be marketed in the United States;^21-23 and

Concerned that U.S. postmarketing surveillance for drug safety lacks a population-based approach to estimating not only the incidence of adverse drug events but also the likelihood of causal relationships between drug exposures and adverse events;²⁴ and

Aware, for example, that federal agency (National Institute of Child Health and Human Development and Food and Drug Administration) appropriations of $31.6 million for trials to determine safety and efficacy in children of 12 generic drugs already in common pediatric use²⁵ will be insufficient to insure appropriateness and safety without studies based on active surveillance of utilization in community populations;²⁶ and

Considering that the influence of pharmaceutical industry marketing activities on both consumers and prescribers²⁷ is not balanced by independent evidence-based information.

Therefore, APHA urges Congress to address the need for independent assessment of pharmaceuticals by adopting legislation to:

1. ascertain the scope and funding of existing avenues, however limited, for the conduct of pharmaceutical assessment research and expand drug evaluation activities, independent of the FDA and of pharmaceutical industry influence; 
2. establish funding for the development of research standards for pharmaceutical assessment and to expand independent assessment of pharmaceuticals, focusing on comparative effectiveness, long-term effectiveness and cost-effectiveness with a societal perspective;
3. mandate and support the development of active surveillance of marketed pharmaceuticals to improve the scientific knowledge base on drug safety; and
4. provide formulary decision-makers, prescribers and the public with access to comprehensive information on marketed pharmaceuticals (strengths and limitations) based on determinations of short- and long-term efficacy and safety as found in clinical trial populations and short- as well as long-term effectiveness and safety data as found in community-treated populations.

References

1. Newhouse JP. Why is there a quality chasm? Health Affairs 2002;21(4);13-25.
2. APHA Policy Statement 9915. Concern about the Food and Drug Administration’s drug approval process. http://www.apha.org/legislative/policy/policysearch/index.cfm?fuseaction=view&id=186. 
3. Guidance for Industry. M4E: The CTD – Efficacy. U.S. Dept. of Health and Human Service, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER). (August 2001). http://www.fda.gov/cder/guidance/4539E.pdf. 
4. Guidance for Industry. E 10 Choice of Control Group and Related Issues in Clinical Trials. U.S. Dept. of Health and Human Service, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER). (May 2001). http://www.fda.gov/cder/guidance/4155fnl.pdf.
5. Drummond MF. Basing prescription drug payment on economic analysis: the case of Australia. Health Affairs 1992;11:191-206.
6. Wolfe SM. Why do American drug companies spend more than $12 billion a year pushing drugs. J. Gen. Intern. Med. 1996;11(10):637-639.
7. Zuger A. Fever pitch: getting doctors to prescribe is big business. New York Times, January 11, 1999.
8. Moore TJ, Psaty TM, Furberg CD. Time to act on drug safety. JAMA 1998;279:1571-1573.
9. Burlington B, Woodcock J, Zoon K, et al. Managing the risks from medical product use. U.S. Food and Drug Administration. May 1999. http://www.fda.gov/oc/tfrm/riskmanagement.html (Accessed Feb. 5, 2003)
10. Strom B.L. What is Pharmacoepidemiology? In: Pharmacoepidemiology, Strom, BL (ed.), 3rd ed., 2000. John Wiley and Sons, Inc., p. 9.
11. Bodenheimer T. Uneasy alliance – clinical investigators and the pharmaceutical industry. N. Engl. J. Med. 2000;342 (20):1539-1544.
12. Dickersin K, Chan S, Chalmers TC, et al. Publication bias and clinical trials. Control. Clin. Trials 1987;8(4):343-353.
13. See reference 11.
14. Safer DJ. Design and reporting modifications in industry-sponsored comparative psychopharmacology trials. J. Nerv. Ment. Dis. 2002;190(9):583-592.
15. Kelch RP. Maintaining the public trust in clinical research. N. Engl. J. Med. 2002;346(4):290-292.
16. Division of Medical Sciences, National Research Council. Drug efficacy study: Final report to the Commission of Food & Drugs. National Academy of Sciences, Washington DC, 1969.
17. Wood AJJ, Stein CM, Woosley R. Making medicines safer – the need for an independent drug safety board. N. Engl. J. Med. 1998;339(25):1851-1854.
18. See reference 14. 
19. Grasela TH. Pharmacoepidemiology: a scientific basis for outcomes research. Ann. Pharmacotherapy 1996:30:188-190. 
20. APHA Policy Statement 20006 (PP). Making medicines affordable: the price factor. http://www.apha.org/legislative/policy/policysearch/index.cfm?fuseaction=view&id=210.
21. See reference 2.
22. Safer DJ, Zito JM, Gardner JF. Pemoline hepatotoxicity and post-marketing surveillance. J. Am. Acad. Child & Adolescent Psychiatry 2001;40:622-629.
23. Bristol-Myers to pull drug in Europe but not in U.S. New York Times, Business/Financial Desk, January 9, 2003 Late Edition - Final, Section C, Column 1, Page 3.
24. Mann RD. Prescription event monitoring. in Strom BL (ed.): Pharmacoepi–demiology, 3rd ed., 2000. John Wiley and Sons, Inc., pp 231-246.
25. Tests are set for adult drugs children take. New York Times, National Desk, January 21, 2003 Late Edition - Final, Section A, Page 14, Column 6.
26. Vitiello B, Jensen PS. Medication development and testing in children and adolescents: current problems, future directions. Arch. Gen. Psychiatry 1997;54:871-876. 
27. See references 6 and 7.

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[发布日期] 2003-11-18

[学科分类] 医学（综合）