Bladder cancer recurrence by implantation of exfoliated cells: is gamma-linolenic acid an effective tumoricidal agent?

PURPOSE: To evaluate the regulatory review interval for recent ophthalmic new drug applications (NDAs) at the U.S. Food and Drug Administration (FDA). METHODS: Based on publicly available information regarding submission and approval dates, the timing of FDA review of NDAs of first indications for therapeutic ophthalmic drugs in the 1990s was evaluated. RESULTS: The mean (median) interval of the 19 NDAs from submission to approval decreased from 44 (18) months in 1990 to 11 (10.6) months in 1996. At least nine of these agents had their first worldwide ophthalmic approval in the United States. For 10 of the 19 NDAs, the ophthalmic NDA represented the first US approval of this molecule by any route. CONCLUSIONS: Quality filings currently appear to be reviewed and approved in 1 year or less. Because of the confidential nature of corporate development, no analysis can be made regarding changes in the presubmission costs and timing.     

The FDA just says yes

Will a new and, some say, improved FDA improve the conditions, financial and otherwise, of patient care? Many argue that the acceleration of the FDA approval process comes at a high price. As new drugs hit the market faster--and with less proof of their long-term benefits--health care costs are going up, up, up, and society is facing painful rationing decisions.     

Health care structure legislation--reform of health insurance

On January 1st, 1993, the German Health Care Structure Reform Act has come into effect. It will fundamentally change the system of health insurance as well as the health care system. By the reform act, new structural and controlling elements have been installed in all central branches of health care, and, at the same time, a new order for the competition between the sickness funds has been established. Far-reaching structural alterations affect the hospital sector, the drug market and the system of ambulatory care. In the hospital sector, there will be a change-over to a price system consisting of special payments, payment according to diagnostic-related groups, and differentiated per-diem rates. On the drug market there will be introduced, besides a drug budget for doctors, a positive list for pharmaceuticals which will be worked out jointly by representatives of the medical profession and the sickness funds. In the ambulatory sector, licensing restrictions for doctors intending to set up practice will be introduced and the importance of the general practitioner or family doctor will be enhanced. The Health Care Structure Reform Act provides for self-government of the sickness funds and the medical profession with a wide range of controlling and shaping instruments. It also places the Ministry of Health in a better position to take influence. After the expire of the budgeting phase, competitive elements resp. extended controlling measures in the contracts sector will become more and more important features of the health care system. It remains to be seen whether the new controlling instruments will suffice to cause the intended limitation of expenditure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Integration of research in pharmacotherapy for addictive disease: where are we? Where are we going?

Systematic efforts by NIDA and NIAAA to develop new medications for drug and alcohol dependence have resulted in recent FDA approval of LAAM for opiate dependence, naltrexone for alcohol dependence and, more recently, a nasal spray for nicotine dependence. This article reviews the current strategies that guide these development efforts, including further examination of the interactions between potential pharmacotherapeutic agents and the drugs of abuse, the enhancement of pharmacotherapeutic efficacy with nonpharmacological interventions, and the development of more precise and meaningful measures of research outcome.     

Depot medroxyprogesterone acetate pioneers. A retrospective study at a North Carolina Health Department

This article examines the characteristics of the first group of depot medroxyprogesterone acetate (DMPA) acceptors after US Food and Drug Administration (FDA) approval of the method and evaluates their continuation rates and factors associated with discontinuation. This was a population based retrospective study based on 12 months of clinic data for 510 women who began using DMPA in 1993 at a large county health department. Cumulative 12 month life table rates were calculated for the entire group and were then stratified by selected characteristics. The 4, 8, and 12 month continuation rates were 67%, 46%, and 35%, respectively. More than half of these women discontinued because of bleeding and nonbleeding side effects (25% and 28%, respectively). Almost 20% of these women were considered discontinuers because they waited longer than 16 weeks to return for an injection. As measured in this study, continuation rates for this first group of DMPA acceptors were low. The next step is to determine if the characteristics and patterns of use of these "pioneer" acceptors are representative of more recent acceptors, and if lessons learned from this group will lead to higher continuation rates.     

Yohimbine for erectile dysfunction: a systematic review and meta-analysis of randomized clinical trials

Well-founded pharmacokinetic information is one of the cornerstones of a New Drug Application (NDA) to the Food and Drug Administration (FDA) required to introduce a new drug or a generic equivalent (ANDA) to the marketplace. The service that laboratories engaged in therapeutic drug monitoring provide to support clinical activities is also needed by the pharmaceutical industry during the evaluation and introduction of drugs to the marketplace. In considering this alternative service activity, one must be aware of and compliant with rules established by the FDA for performance of such studies. As specified in CFR 21, Parts 58, 211, and 320, good clinical and laboratory practice indicates that the laboratory should employ a Lab Study Director, who is responsible for the validation of all procedures implemented to support a study protocol, ensures that the laboratory carries out the study following these defined procedures, and personally reviews the results of all testing. The laboratory must validate each procedure by demonstrating and documenting that the procedure does what it is designed to do while meeting the analytical performance specifications required by the study. Laboratory records of all activities must be maintained and available for inspection by the FDA on request. The FDA has authority over all activities related to NDA and ANDA submissions and can bring criminal charges if results of a study are changed because a laboratory deviates from standard procedure. Competent drug monitoring laboratories are fully capable of participating in clinical trials testing activities. Laboratory staff should be fully versed in the FDA rules governing these activities, validate all procedures, and establish systems to verify the procedures are carried out as specified.     

Diagnostic value of bone and Ga-67 imaging in skeletal tuberculosis

In the future, U.S. military forces will be faced with opposing forces that have chemical and biological weapon capabilities. Although drugs used against these agents would be an ideal solution to protecting soldiers, the ability to test their efficacy in humans is limited by several ethical and technical problems: (1) the high risk of toxicity to volunteers; (2) the risk of delayed side effects in the volunteers; and (3) the inability to extrapolate effects against sublethal doses to efficacy against lethal doses. The Food and Drug Administration (FDA) relies on safety and efficacy data in humans, making approval for these types of drugs difficult. An alternative approach for regulatory approval would be to use surrogate markers. Surrogate markers are biochemical or physiologic measurements that demonstrate the direct effect of the drug. Surrogate markers, such as CD4 counts and viral RNA levels, have been used recently in the anti-human immunodeficiency virus drug approval process with success. A drug development program using surrogate markers must meet several criteria, including demonstrated efficacy in animal models, correlation between efficacy and the surrogate marker, a link between the surrogate marker and the pathophysiology and toxicologic effects of the agent, and the ability to produce the surrogate marker in humans. This article illustrates the use of drug-induced methemoglobin as a surrogate marker for protection against cyanide intoxication. Safety issues regarding this class of drugs would also have to be pursued aggressively during and after their use by military forces. Demonstrating that the drug satisfies these criteria would be a platform for approval by the FDA. The guidelines mentioned above should be an acceptable approach for FDA approval, scientific researchers, medical practitioners, and the soldiers using these drugs.     

New therapeutic agents marketed in 1993

In 1993, the Food and Drug Administration (FDA) approved 25 new molecular entities (NMEs), 23 of which are for therapeutic use and two are diagnostic agents. Eleven of the NMEs for therapeutic use, as well a new biological agent intended for therapeutic use, were both approved and marketed in the United States in 1993. In addition, 11 other NMEs that the FDA approved before 1993 (most in late 1992) were marketed during the year. Thus, a total of 23 therapeutic agents reached the U.S. market for the first time in 1993, a considerably lower number than the 30 new therapeutic agents marketed in 1992 and the record number 31 new agents marketed in 1991. Many of the 13 therapeutic agents approved in 1993 but not marketed before the end of the year have become available in early 1994. This review of the therapeutic agents first marketed in 1993 considers their most important properties and, when possible, compares them with other available agents with similar properties. Of the 23 new therapeutic agents, 22 are considered in this paper. The one agent not reviewed is flosequinan, which was withdrawn from the market after being available only several months because of a concern about toxicity. This discussion of new drugs focuses on the most important properties of these agents; when additional information is needed, more comprehensive references and the product literature should be consulted.     

A drug revolving fund program for rural villages in the Philippines

In 1994, a community-based drug revolving fund program was introduced in 10 pilot villages in the province of Tarlac, Philippines, as a component of a health project by the provincial health office and Japan International Cooperation Agency (JICA). The purpose of the program was to set up a cooperative drug store in each community in order to regularly provide rural residents with essential drugs at affordable prices. The following are the results and findings during the first two years of operation. 1. Collaboration with a local NGO facilitated implementation and management of the program, when socio-cultural consideration was necessary. Stable and prompt procurement of drugs was secured on a contract with a commercial wholesaler in Manila. 2. Out of the 105 kinds of pharmaceuticals that were sold both in the cooperative and commercial drug stores, 83% were less expensive than the average market price, and 51% were discounted more than 25% of the market price. 3. The levy of premiums was introduced to increase the cooperative fund with the consent of each community. The amount was 0.1-0.2% of the average family income. However, regular collection of premiums was difficult due to various reasons. The practice of the sales on credit was common in all pilot villages. 4. While the knowledge of community health workers, who were in charge drug sales, was improved after training sessions on rational drug use, it was not at a sufficient level yet. 5. When assisting a community-oriented health program, an exterior organization should try to encourage the community to generate its own solutions to operational difficulties, based on the socio-cultural context in the community.     

Declining seroprevalence in a very large HIV epidemic: injecting drug users in New York City, 1991 to 1996

OBJECTIVES: This study assessed recent trends in HIV seroprevalence among injecting drug users in New York City. METHODS: We analyzed temporal trends in HIV seroprevalence from 1991 through 1996 in 5 studies of injecting drug users recruited from a detoxification program, a methadone maintenance program, research storefronts in the Lower East Side and Harlem areas, and a citywide network of sexually transmitted disease clinics. A total of 11,334 serum samples were tested. RESULTS: From 1991 through 1996, HIV seroprevalence declined substantially among subjects in all 5 studies: from 53% to 36% in the detoxification program, from 45% to 29% in the methadone program, from 44% to 22% at the Lower East Side storefront, from 48% to 21% at the Harlem storefront, and from 30% to 21% in the sexually transmitted disease clinics (all P < .002 by chi 2 tests for trend). CONCLUSIONS: The reductions in HIV seroprevalence seen among injecting drug users in New York City from 1991 through 1996 indicate a new phase in this large HIV epidemic. Potential explanatory factors include the loss of HIV-seropositive individuals through disability and death and lower rates of risk behavior leading to low HIV incidence.     

Relationships between the academic community and the pharmaceutical industry: the legislative background and its effect on spending on medical research and development

Patent legislation governing drugs has evolved through a series of amendments to the Patent Act. From 1923 until 1993, Canada operated a system of "compulsory licensing," allowing generic copies of patented medicines to be manufactured within Canada and, by 1969, to be imported. In 1987, the act was amended (Bill C-22) to provide patented medicines with a fixed period of market protection before a compulsory license could be issued and to create a price review board to monitor and control prices charged. In return for patent protection, brand-name drug companies promised to invest a growing percentage of sales revenue in research and development in Canada. A 1993 amendment to the Patent Act (Bill C-91) brought a fundamental change to the legislation by abolishing the system of compulsory licensing and applying general patent regulations to medicines, thereby bringing Canadian law into line with that of its trading partners. It is now illegal to sell a copy of a drug until the patent expires (20 years after the patent is filed). This means that marketed drugs are protected for 8 to 13 years, since drug development takes a large proportion of the life of the patent. Since this amendment was passed, the brand-name drug companies have made major contributions to research and development in Canada, increasing from 6.5% of sales revenue in 1987 to 11.6% in 1994. Major irritants in the legislation remain. Generic drug companies have complained about "linkage regulations" that allow brand-name drug companies to legally challenge generic drug production on the basis of alleged infringements of linked patents, delaying the marketing of the generic drug. The act also prohibits Canadian manufacturers from exporting a generic drug to a country where it is not protected if it still protected in Canada. Brand-name manufacturers want some means of patent term restoration if regulatory authorities prolong the time taken before marketing a drug. This legislation is being reviewed by parliament beginning in 1997.     

The selling of olestra

The Procter & Gamble Company spent 30 years and an estimated $500 million to bring its non-digestible fat substitute, olestra, to market. The Food and Drug Administration approved olestra as a food additive but requires products containing olestra to carry a warning statement about its potential effects on gastrointestinal function. In obtaining approval for olestra, P&G conducted a lengthy, persistent, and comprehensive campaign to enlist support from members of Congress; FDA staff; and food, nutrition, and health professionals. This campaign raises larger questions about corporate influence on government policies, and the relationships of corporations to health professionals. To address these larger concerns, the author reviews the history of olestra's approval; describes P&G's campaign to obtain support from FDA and Congress, to defend olestra against critics, and to market it to professionals, the press, and consumers; and suggests implications for public health policies.     

Impact of Phase Shifters on Locational Prices

With the introduction of restructuring in the electric power industry, the price of electricity has become the focus of power market activities. Phase shifters in a power system can mitigate or reduce transmission congestion by redirecting line flows, reduce the cost of power dispatch by adjusting locational marginal prices (LMPs), and enhance market competition by reducing the chance of market power occurrences due to limited transmission flows. This paper analyzes the role of phase shifters in restructured power systems by simulating electricity market prices. The paper further provides a comparison among various alternatives such as transmission expansion for mitigating congestion. The simulation results are analyzed for a three-bus and presented for the Institute of Electrical and Electronics Engineers (IEEE) 118-bus power system.     

Effects on the Metals Industries of the Decrease in Oil Prices: A Preliminary Analytical Survey∗

The recent decrease in oil prices should benefit metals producers by reducing costs of production—through lower energy prices—and increasing the demand for metals— through income and substitution effects. It is difficult, however, to predict a substantial return to the earlier relative role of metals: Real energy prices are still well above their levels of 20 years ago; the duration and extent of the oil price decrease is highly uncertain; petroleum generally is not a very important energy input in metal production; other energy prices probably will not decline as much as oil prices; and the effects of the oil price decrease on currency exchange rates and inflation rates are complex and difficult to predict in general and for individual countries.     

Pharmaceutical regulation in the single European market

This paper assesses the impact of new EU-wide drug authorisation procedures. The paper examines various attempts to introduce harmonised market authorisation routes for pharmaceuticals including the establishment of the multi-state, concentration, decentralised and centralised procedures. The paper considers the current role of the European Medicines Evaluation Agency and the likelihood that its powers will be increased in the future. Finally, the paper assesses whether EU regulation has created beneficial market conditions for pharmaceutical companies operating in the single European market.     

工程量清单计价模式在招标中的应用

工程量清单计价模式是以工程量清单报价为平台的新的计价模式 ,在“边设计、边投资、边施工”工程招标中 ,应采取积极策略应对 ,以便在建筑市场竞争环境中合理合法地保护建设单位的经济利益     

Human papillomavirus as an etiological factor in cervical cancer: significance for health care practice

The migration of substances from rubber packaging materials into drug products can be significant with certain packaging materials in contact with organic solvent systems. Recommendations for testing drug products for leachables are continually evolving to address new developments. Testing packaging materials using simulated solvents is not always an acceptable protocol for the pharmaceutical industry. We describe a rational strategy for evaluation of the drug product for packaging extractables. A profile of the extractables from rubber packaging materials was made with a range of organic solvents and stress conditions to provide information on substances to target in the drug product. The drug product was evaluated to determine if the matrix would cause interferences that might inhibit detection of the found extractables. Analytical methods were selected based on these findings. The procedures were validated according to FDA guidelines. A stability program using time and storage conditions as variables provided information for acceptance criteria. This same strategy can be used on other types of pharmaceuticals and packaging materials.     

新经济形势下铜市场展望

在欧洲主权债务危机深化、发达经济体衰退、新兴经济体通胀、自然灾害频发、政局动荡等诸多因素相互作用和影响下,2011年下半年,铜价大幅下挫,相比年初铜价跌幅最大达到32%。在如此新经济形势下,供需关系已不仅仅是影响铜市场走势的唯一因素,甚至在某些时间段,也成为不了主导因素。铜市场如何走向,2012年铜价会不会大幅下跌,成为铜企业管理者及铜期货及基金工作者关注的焦点。本文从全方位的视角分析了"新经济形势"下影响铜市场走势的因素,详细说明了铜市场供需面影响因素,对2012年铜市场进行了展望。     

黄金产量与市场价格的关系分析

影响黄金价格的因素很多也很复杂,分析国际金价的方法也是见仁见智,但是许多分析人员和投资者,一般都会把世界黄金产量的变化作为影响黄金价格的一个重要因素。文中通过黄金的特殊性质、地面存金对黄金市场供求关系的影响,以及黄金作为商品的特殊消费模式等方面的分析,阐明了黄金产量的变化对国际金价的影响是非常有限的。