Volume 49 Issue 1
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Table of Contents
> Clinical Research Center for Rare Diseases
Villa Camozzi
> Are Pharmaceutical Ads Deceptive?
> Misleading Research on the Subject of Misleading
Advertising: The Wilkes et al. Investigation of Pharmaceutical
Advertising in Leading Medical Journals
>Determining Appropriate Reimbursement for
Prescription Drugs: Off- Label Uses and Investigational Therapies
> Practical Considerations in Direct Interactions
Between Sponsors and Institutional Review Boards
> The History, Provisions, and Implementation
of the Generic Drug Enforcement Act of 1992
> Court Secrecy and the Food and Drug Administration:
A Regulatory Alternative to Restricting Secrecy Orders in
Product Liability Litigation Involving FDA-Regulated Products
> EC Harmonization of the Licensing and Manufacturing
of Medicinal Products
> International Memoranda of Understanding
on Inspections
> An Overview from the Director of the Center
for Devices and Radiological Health
> Amplification of Federal Preemption in Medical
Device Cases
> Regulation of Biologics Manufacturing: Questioning
the Premise
> From A History of Near Misses: The Future
of Dietary Supplement Regulation
> Distinguishing Between Research and Medical
Practice During Operation Desert Storm
> Should You Take an Activist to Breakfast?
Authors: Silvio Garattini and Giuseppe Remuzzi
Issue: 48, 49 Food and Drug Law Journal 1-6 (1994)
The Mario Negri Institute for Pharmacological Research is a non-profit foundation established in 1963 in Milan to study human diseases, with particular emphasis on the mechanism of action of drugs. The Institute--aside from the original in Milan, there are two other research centers--recently has established a Clinical Research Center, aimed at the development of research projects in the area of rare diseases. Few specialized areas of medicine are as neglected today as rare disease research. The best way to achieve adequate scientific information in this field is to develop laboratory and research projects. The Clinical Research Center is housed in an 18th century villa, called Villa Camozzi, in Ranica, northern Italy. The house is under restoration, but a wing is already fully equipped to host patients for one-day clinical studies, ambulatory visits, and consultations. The Clinical Research Center for Rare Diseases will provide: 1) an information center for rare disease, 2) a clinical research center with facilities for outpatients, inpatients, and day-hospital, and 3) the European School for Rare Diseases, to be operational by 1995.
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Are Pharmaceutical Ads Deceptive?
Author: Paul H. Rubin
Issue: 49 Food and Drug Law Journal 7-20 (1994)
A recent article in the Annals of Internal Medicine has received substantial press attention and is the basis for serious policy proposals to require preapproval of all advertisements for pharmaceuticals in medical journals. An analysis of the study from the perspective of the economics of information reveals that there are serious flaws in this study, and it should not be used as the basis for any policy decision. The study asked expert physicians and pharmacists to evaluate ads. The investigation used inappropriate criteria for this evaluation: FDA standards of deception use terms of art, and outsiders not trained in their use cannot determine if they are being violated; it is inappropriate to assume that physicians have no information other than that found in an ad; and advertisements cannot meaningfully be judged by the same criteria used for peer review of journal articles. The study used its data in a biased manner. Results were presented in a confusing way, and some of those promoting the study were themselves misled by the method of presentation. Most importantly, other evidence indicates that physicians are too conservative with respect to prescribing behavior, so that use of a proper endpoint would suggest that physicians need more, not less, information. Therefore, reduced, not increased, regulation of advertising is required for optimal public health.
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Misleading Research on the Subject of Misleading Advertising: The Wilkes et al. Investigation of Pharmaceutical Advertising in Leading Medical Journals
Author: Jacob Jacoby
Issue: 49 Food and Drug Law Journal 21-36 (1994)
Based upon a survey of physicians and clinical pharmacists, a recent article in the Annals of Internal Medicine concluded that pharmaceutical advertising appearing in medical journals is frequently misleading. This article reviews the conceptual and empirical foundations on which that conclusion was based and finds both to be severely flawed. While too high a proportion of prescription drug advertising may in fact be misleading, the aforementioned survey provides no scientifically defensible basis on which to draw such a conclusion.
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Determining Appropriate Reimbursement for Prescription Drugs:
Off-Label Uses and Investigational Therapies
Author: Drusilla S. Raiford, Sheila R. Shulman and Louis Lasagna
Issue: 49 Food and Drug Law Journal 37-76 (1994)
Through increasingly rigorous determinations of what will and will not be paid for, third-party payors have been affecting the nature, quality, and quantity of health care services. A reassessment of prescription drug benefits has been an integral part of this process for some time. This study was undertaken to examine third-party payors' efforts to tailor their coverage and reimbursement for "appropriate" drug therapies. Emphasis was placed on policies related to off-label use of approved drugs, with some attention to coverage for investigational drugs.
The report presents the results of two surveys. The first examines four pharmaceutical compendia, three of which, both formally and informally, have emerged as primary resources for the reimbursement of off-label indications. A slightly expanded variation of this practice is included in the Omnibus Budget Reconciliation Act of 1993 and in the proposed Health Security Act, S. 1757. The second survey was directed to public and private third-party payors to assess internal institutional efforts to define pharmaceutical reimbursement policies.
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Practical Considerations in Direct Interactions Between Sponsors and Institutional Review BoardsAuthor: David M. Cocchetto
Issue: 49 Food and Drug Law Journal 77-88 (1994)
Direct interaction between a sponsor and an institutional review board (IRB) occurs in few circumstances that are explicitly recognized in regulations. Food and Drug Administration (FDA) regulations explicitly require direct sponsor-IRB interaction only when a sponsor discontinues a study for safety reasons, withdraws an investigational new drug application (IND) for safety reasons, or is faced with an IRB requiring verification that no changes in the research activity have been initiated without the IRB's knowledge. Other direct sponsor-IRB interactions are not explicitly recognized in regulation, but such interactions most often arise from the efforts of the sponsor, monitor, investigator, and IRB to meet their interdependent medical and regulatory obligations. These interactions usually are for purposes of mediation, suspicion of misconduct, investigation, facilitation of communication, or discussion of business agreements. Examples of each type of interaction were assembled from several sponsor organizations and IRBs. In many situations, the clear utility of such interactions is apparent. This discussion and the examples therein define state-of-the-art direct sponsor-IRB interactions.
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The History, Provisions, and Implementation of the Generic Drug Enforcement Act of 1992
Author: John R. Fleder
Issue: 49 Food and Drug Law Journal 89-108 (1994)
The Generic Drug Enforcement Act of 1992 (GDEA) was enacted to correct a corrupt approval process for generic drugs through abbreviated new drug applications (ANDAs). The legislative history of the GDEA provides insight into Congress' intent. The Food and Drug Administration (FDA) believes that the GDEA's debarment provisions are retroactive, but a recent Supreme Court decision casts doubt on that position. The FDA has just begun to implement the GDEA. Congress will monitor the agency's actions closely, and consequently, industry can expect the FDA to take a strong enforcement stand.
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Author: Dorothy J. Clarke
Issue: 49 Food and Drug Law Journal 109-140 (1994)
This article proposes an amendment to the Federal Food, Drug, and Cosmetic Act that would require drug and device manufacturers to submit information to the Food and Drug Administration (FDA) regarding product liability litigation. The proposed amendment would serve as an alternative to current reform proposals that severely restrict secrecy orders when public health or safety is implicated. The article focuses on the impact of protective orders on the dissemination of information about hazardous products to the government and the public, describes current practice regarding secrecy orders, and summarizes arguments for and against their use. It then examines recent legislative activity at the federal and state levels regarding the restriction of secrecy orders in product liability cases. Next, the article examines current FDA reporting regulations and proposes new regulations that would require reports regarding product liability litigation. The proposed provisions would require drug and device manufacturers to compile quarterly litigation reports describing all suits where serious injury or death is alleged. The FDA would then monitor this information and conduct further investigations when merited. Finally, the article examines the effect of the author's proposal on the various interests involved, comparing the proposed regulatory reform to current legislative reforms.
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EC Harmonization of the Licensing and Manufacturing of Medicinal Products
Author: Evelyne Friedel and Michael Freundlich
Issue: 49 Food and Drug Law Journal 141-170 (1994)
Substantial efforts made by the European Community (EC) to create a single borderless market in 1993 have resulted in the harmonization of national rules governing the licensing and manufacturing of medicinal products. As to licensing, the recent legislative changes shall enter into effect in 1995. A centralized procedure for new medicinal products, as well as products based on biotechnology and high technology, has been established. For all other products, a decentralized procedure will apply. While these two procedures are based on the previous ones (concertation and mutual recognition), they substantially improve the process for obtaining Community-wide marketing authorization. In addition, a European counterpart to the Food and Drug Administration, the European Agency for the Evaluation of Medicinal Products, has been established and is based in London. As to manufacturing authorizations, national rules have been harmonized since 1991 through common standards of good manufacturing practice. The new European Agency will ensure compliance with these standards throughout the Community.
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Author: Philip B. White
Issue: 49 Food and Drug Law Journal 171-174 (1994)
The Food and Drug Administration (FDA) has a strong and continuing interest in the area of international good manufacturing practices inspections. A recent report from the FDA's Task Force on International Harmonization recommended that the agency develop policies that will enhance international cooperation in enforcement and compliance. This article discusses one means of accomplishing this cooperation, namely international memoranda of understanding on inspections.
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An Overview from the Director of the Center for Devices and Radiological Health
Author: D. Bruce Burlington
Issue: 49 Food and Drug Law Journal 175-182 (1994)
This article discusses the organizational changes in the Food and Drug Administration's (FDA's) Center for Devices and Radiological Health (CDRH), from the perspective of the Center Director. It focuses on changes made in CDRH personnel and Center infrastructure, and on the development of CDRH policies surrounding premarket review, compliance, and postmarket management.
Amplification of Federal Preemption in Medical Device CasesAuthor: Lars Noah
Issue: 49 Food and Drug Law Journal 183-212 (1994)
By virtue of the express preemption provision in the Medical Device Amendments, devices are unique among products which are subject to Food and Drug Administration (FDA) regulation. In addition to preventing direct state regulation in most circumstances, courts have applied this provision to dismiss products liability claims arising under state common law. In recent years, the federal preemption defense in lawsuits involving approved Class III devices has become fairly well settled. The most important issue in future cases will be the extent to which FDA determinations to allow product marketing short of premarket approval will entitle a manufacturer to interpose a preemption defense on that ground alone. The increasingly rigorous review of premarket notifications under section 510(k) of the Act may provide a basis for the same sweeping preemption of claims that has been recognized with regard to approved Class III devices.
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Regulation of Biologics Manufacturing: Questioning the Premise
Author: Gary E. Gamerman
Issue: 49 Food and Drug Law Journal 213-236 (1994)
For many reasons, historic and scientific, the regulatory restrictions that control biologics manufacturing are more limiting than those that control drug manufacturing. Recently, the Center for Biologics Evaluation and Review (CBER) revised its policy on cooperative manufacturing arrangements for biologics, to ameliorate some of the effects of preexisting policies. However, other changes are needed and justified by modern biopharmaceutical manufacturing technology. This article address the question of whether unique regulation of biologics under the Public Health Service Act section 351 continues to serve a useful purpose. It suggests that regulatory and public health goals might be better served by consolidation of biologics regulation with the controls placed on pharmaceutical manufacturing under the Federal Food, Drug, and Cosmetic Act.
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From A History of Near Misses: The Future of Dietary Supplement Regulation
Author: Mark A. Kassel
Issue: 49 Food and Drug Law Journal 237-270 (1994)
In the wake of increased awareness of dietary health issues that has resulted in such measures as the Nutrition Labeling and Education Act of 1990 and the establishment of the Dietary Supplement Task Force, this paper examines the history, evolution, and potential regulation of dietary supplements. Possible harmful effects to the American public from unregulated dietary supplements are discussed. The Food and Drug Administration (FDA) repeatedly has attempted to regulate vitamins, minerals, and other supplements, and has been unsuccessful. This paper proposes reasonable methods by which the FDA or other government organizations may effectively monitor the content, potency, and labeling claims made by producers and distributors of dietary supplements.
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Distinguishing Between Research and Medical Practice During Operation Desert Storm
Author: Elliott J. Schuchardt
Issue: 49 Food and Drug Law Journal 271-290 (1994)
During Operation Desert Storm, the Department of Defense required American soldiers to take investigational drugs as pretreatment antidotes to Iraqi chemical and biological weapons. Although these drugs had not been approved by the Food and Drug Administration, the Pentagon did not obtain the soldiers' informed consent before administering the drugs. The author analyzes whether this action violated the Defense Authorization Act of 1985, which prohibits the Pentagon from conducting "research" on nonconsenting soldiers. The article explores the legislative history of the Act to locate the line between "research" and medical "practice." It determines that Congress meant to adopt the definition of research formulated by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The Commission determined that research was characterized by two factors: the risk of the procedure and the intent of the physician. After determining that this was Congress' meaning, the author concludes that the Department of Defense did not violate the Defense Authorization Act by conducting "research" on the soldiers during Operation Desert Storm.
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Should You Take an Activist to Breakfast?
Author: Henry Spira
Issue: 49 Food and Drug Law Journal 291-299 (1994)
Corporations may be more vulnerable to advocacy campaigns than they realize. Image often is a corporation's major asset, and billions of industry dollars are spent on advertising and public relations to create and protect a positive identity. When such image-conscious corporations are unresponsive to emerging consumer concerns, however, they may become vulnerable to well-planned activist campaigns. Effective advocates study the realities and ambiguities of the public they seek to influence. They find sub-issues that are winnable, that is, the issues are personal enough to generate public energy while incrementally moving the larger issue toward a broad resolution. Pragmatic activists set priorities, maintain credibility, develop realistic campaign blueprints, seek dialogue and joint efforts to solve problems, suggest viable alternatives, and are prepared for relentless confrontation if there is no response through accepted channels. An effective working relation is based on corporate decision makers doing more than providing access or taking activists out for breakfast; it is based on serious responsiveness to the concerns under discussion. Activist case studies are discussed in this article, based on personal experiences of the author, that range from working partnerships to escalating confrontation.
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