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Biomedical subjects

K I Kaitin

Publications and source records attributed to K I Kaitin.

At least 19 recordsLinked to original sources
PubMed2000

New drug approval times and 'therapeutic potential' in Canada, Australia, Sweden and the United States during the period 1992 to 1998.

In two previous studies, the times required to approve new drugs in Canada, Australia, Sweden, the United Kingdom and the United States during the periods 1992 to 1995 and 1996 to 1998 were compared. However, during each of these two periods, only a fraction of the drugs that were approved in any of the countries were approved in all of them. Because an analysis based solely on drugs approved in all the countries would provide additional information, data from the previous studies have been used to compare drugs approved in each of Canada, Australia, Sweden and the United States during the period 1992 to 1998. In addition, applications that received a 'priority' or a 'standard' review by the United States Food and Drug Administration were analyzed separately to determine whether differences between the countries diminished for drugs considered to be of potentially greater therapeutic value. For the 87 drugs identified as being approved for marketing in all four countries during the period 1992 to 1998, approval times in Canada and Australia were not significantly different, but both Canada and Australia had significantly longer times than those of the United States and Sweden (P<0.001). Of the 87 drugs, 37 (43%) received a priority review in the United States. In both the priority and standard review categories, the Australian and Canadian median approval times were significantly longer than those in Sweden and the United States. The results demonstrate that, in general, both priority and standard new drug applications are reviewed more expeditiously in Sweden and the United States than in Canada. Canadian patients continue to experience delayed access to potentially valuable medicines.

Australia↗
PubMed1997

The new drug approvals of 1993, 1994, and 1995: trends in drug development.

Growing concern within Congress, the pharmaceutical industry, and the Food and Drug Administration (FDA) over the excessive time and cost required to develop new drugs and bring them to market has led to several initiatives designed to speed the drug development process, e.g., the Prescription Drug User Fee Act of 1992 and recent efforts at legislative reform of the agency. To assess the impact of these initiatives, it is useful to examine recent trends in new drug development and review. This report is the fourth in a series in which we analyze new chemical entities (NCEs) recently approved by the FDA. In 1993, 1994, and 1995, the FDA approved 75 new drugs, 67 of which met the Tufts Center's definition of an NCE. Of the 67, 31 (46%) received priority review, 13 (19%) had orphan drug status, and 5 (7%) were approved under the accelerated approval regulations. For the 67 NCEs, the mean length of the clinical phase (investigational new drug filing to new drug application submission) was 7.1 years, and the approval phase (new drug application submission to approval) was 2.0 years. The mean approval phase for the 31 priority NCEs (1.5 years) was 38% shorter than that for the 36 standard NCEs (2.5 years). Compared with similar values for the previous 3-year period, the mean clinical phase for all NCEs increased by 16%, whereas the mean approval phase decreased by 23%. Of the 66 NCEs for which foreign marketing data were available, 34 (52%) were available in foreign markets one or more years prior to U.S. approval, with a mean of 7.7 years of earlier foreign marketing.

Drug Approval↗
PubMed1996

The Prescription Drug User Fee Act of 1992. A 5-year experiment for industry and the FDA.

The Prescription Drug User Fee Act of 1992 authorises the US Food and Drug Administration (FDA) to collect in excess of $US332 million in user fee revenues over a 5-year period. Not only did Congress determine that the revenues would be dedicated to expediting the FDA's review of human drug applications, the FDA articulated formidable time-specific performance goals to be achieved by fiscal year 1997. At the mid-point in the 5-year programme, the FDA reported that it had met or exceeded its performance goals. In this article, we review the history of the user fee scheme in the US, outline the details of the legislative provisions, and discuss the challenges confronting the agency as it works to simultaneously meet the user fee goals and respond to political forces calling for substantive FDA reform. User fees loom large for the global pharmaceutical and biotechnology industries as economic pressures force a number of countries to consider shifting a portion of the cost of regulatory review to the regulated industry. This article provides a reference on the US framework and may be useful in future international comparisons as the user fee phenomenon spreads.

Drug Industry↗
PubMed1995

Drug safety discontinuations in the United Kingdom, the United States, and Spain from 1974 through 1993: a regulatory perspective.

The objective of the present study was to compare the number of new chemical entities (NCEs) and new biologicals entities (NBEs) approved for marketing during the period 1974 through 1993 in the United Kingdom, the United States, and Spain that were subsequently discontinued (removed from the market, withdrawn, or whose license was allowed to lapse) while a question of safety existed. Of the products approved during the two decades of the study period, a total of 29 drugs were subsequently discontinued for safety reasons in at least one of the three countries (United Kingdom: 20 safety discontinuations; United States: 10; and Spain: 16). These represent 3% to 4% of all drugs introduced in these countries, an increase compared to the period from 1964 through 1983, when approximately 2% of all NCEs were discontinued for safety reasons. The therapeutic classes most commonly associated with safety discontinuations were the nonsteroidal anti-inflammatory drugs (nine drugs), vasodilators (four drugs), and antidepressants (three drugs). U.S. companies or their foreign subsidiaries were involved as originators (patent-holders and/or developers) of approximately 40% of the drugs discontinued for safety reasons.

Animals↗
PubMed1994

The new drug approvals of 1990, 1991, and 1992: trends in drug development.

Efforts to speed the development and review of new drugs have increased sharply in recent years. This report, which is the third in a series on trends in drug development, examines the new drug approvals of 1990, 1991, and 1992. During the 3-year study period, the Food and Drug Administration (FDA) approved 79 new drugs, 74 of which met the Center for the Study of Drug Development's definition of a new chemical entity (NCE). Of the 74 NCEs, 36 (49%) were considered by the FDA to represent notable therapeutic gains and were selected for "priority" review (i.e., drugs rated 1P, 1A, 1AA, and 1B), and 38 (51%) were considered to represent little or no gain and received "standard" reviews (i.e., drugs rated 1S and 1C). Investigational new drug application (IND) filing and new drug application (NDA) submission dates on all 74 drugs were obtained from responses to our manufacturer surveys as well as from FDA and public sources. The mean length of the clinical phase (IND filing to NDA submission) was 6.1 years and that of the review phase (NDA submission to approval) was 2.6 years. Of the 74 NCEs, 43 (58%) were available in foreign markets at least 1 year before U.S. approval, with a mean of 5.6 years of foreign marketing. In general, 1990 to 1992 figures are similar to those in the last half of the 1980s.

Drug Approval↗
PubMed1993

The role of the research-based pharmaceutical industry in medical progress in the United States.

The development of innovative new drugs is a time-consuming, expensive, and risky process. Despite these challenges, the pharmaceutical industry has been remarkably successful in developing a broad range of important new medicines. This report examines several aspects of new drug development in the pharmaceutical industry and provides a quantitative evaluation of the role of the drug industry in medical progress. Results indicate that of the 196 new chemical entities approved by the FDA from 1981 through 1990, the source of 92% was the pharmaceutical industry. Within the industry, there was a sizeable increase in the level of clinical research activity (based on the number of investigational new drug [IND] filings) from the mid-1970s to the mid-1980s; moreover, for U.S.-owned firms IND filings increased 46% between 1976 and 1989. Analysis by therapeutic category indicates that much of this clinical research activity was directed towards the development of drugs for cardiovascular disease and mental illness, and more recently towards the treatment of cancer and acquired immunodeficiency syndrome (AIDS). These represent therapeutic areas in which there is an urgent need for new and more effective medicines. The high level of research activity was also reflected in the relative number of drug approvals in these areas. It is hoped that the present findings will contribute to the current debate on drug policy issues and encourage policy-makers to consider what impact proposed health care policies might have on pharmaceutical innovation.

Drug Industry↗
PubMed1992

Pharmaceutical regulation in the European Community: barriers to single market integration.

The European Community (EC) plans to create a single market for pharmaceutical medicines, but the drug industry is closely linked to cultural and societal values concerning health; to the national regulatory agencies responsible for the evaluation of safety, quality, and efficacy of new drugs; to multinational and domestic companies competing in national and international markets; and to varied interest groups of professionals and consumers organized along national and multinational lines. We review the history of the EC's policy proposals, examine reactions from all these interested parties, and assess the prospects for integration into a single market. The contentious debate that continues among the parties over national prerogatives, industrial interests, professional mandates, and consumer concerns clouds the prospects for a system of centralized drug registration that will be acceptable to all EC member states.

Community Participation↗
PubMed1991

Therapeutic ratings and end-of-phase II conferences: initiatives to accelerate the availability of important new drugs.

To facilitate the availability of important new therapeutic agents, the Food and Drug Administration (FDA) in the mid-1970s began assigning therapeutic ratings to investigational new drugs and holding end-of-phase II conferences with drug sponsors. To determine whether these initiatives are associated with faster approvals, we examined new drug application (NDA) review times of new chemical entities (NCEs) approved during the 12-year period 1978 through 1989. Mean NDA review time for 1A drugs (22.5 months) was 22% shorter than that for 1B drugs (28.7 months), which in turn was 25% shorter than that for 1C drugs (38.4 months). For drugs approved during the recent 4-year period 1986 through 1989, however, the gap between 1A and 1C review times has narrowed considerably from 19 to 9 months. When drugs were grouped by FDA reviewing division, 1A drugs had the shortest mean review time in each division except the Cardio-Renal Division; in that division, 1B drugs had the shortest mean review time. Mean NDA review time for drugs that had end-of-phase II conferences (28.6 months) was 15% shorter than that for drugs without such conferences (33.7 months). These results suggest that NCEs that receive 1A or 1B ratings and are the subject of end-of-phase II conferences benefit by having shorter review times.

Drug Evaluation↗
PubMed1991

The new drug approvals of 1987, 1988, and 1989: trends in drug development.

The new drug approvals of 1987, 1988, and 1989 were analyzed to determine whether there are any emerging trends in the US drug development and review processes. Sixty-four new drugs were approved by the FDA during this period, of which 55 met the Center for the Study of Drug Development's definition of a new chemical entity (NEC). For the 55 NCEs, the mean length of the investigational new drug application (IND) phase (IND filing to NDA submission) was 5.2 years, the new drug application (NDA) phase (NDA submission to approval) was 2.9 years, and the total phase (IND filing to NDA approval) was 8.1 years. Nine of the 55 NCEs were classified by the FDA as 1A (important therapeutic gain), 15 were classified as 1B (modest gain), 29 were classified as 1C (little or no gain), and 2 were classified as 1AA (drugs to treat AIDS and AIDS-related conditions); 10 drugs were granted orphan status. The mean NDA phase for 1A drugs was 2.4 years; 1B drugs, 2.9 years; 1C drugs, 3.1 years; 1AA drugs, 1.4 years; and orphan drugs, 2.5 years. Forty-four of the 55 NCEs (80%) were available in foreign markets before US approval was given, with a mean of 6.5 years of prior marketing. These data are consistent with figures for previous years and suggest little change in the rate of new drug development and review in the United States.

Drugs, Investigational↗
PubMed1991

New indications for already-approved drugs: an analysis of regulatory review times.

A survey of the U.S. pharmaceutical industry was conducted to obtain data on the length of the review process for supplemental indications of already-approved new chemical entities (NCEs). Responses were received from 51 firms and covered supplemental indications of 348 NCEs that were approved during 1963 to 1988. Since extensive toxicity and safety evaluation would generally not be required for supplemental indication reviews, one would expect supplemental indications, on average, to be reviewed more quickly than applications for the associated original indications. The mean +/- standard deviation review time for the 172 supplemental indications in the sample is 21.5 +/- 18 months; the average review time for the associated 94 original indications is 23.5 +/- 18 months. The difference in average review times is not statistically significant. Analysis of review times for indications grouped by Food and Drug Administration (FDA) reviewing division showed a statistically significant difference between supplemental and associated original indication review times only in the cardio-renal division. In that division, average review times were longer for supplemental indications (25.6 vs. 19.3 mo; P less than .05). Analysis of time trends showed a significant increase in average supplemental indication review time for 1985 to 1988 approvals relative to the average associated original indication review time (P less than .01) and to average supplemental indication review time for earlier time periods (P less than .01). These results suggest the need for a close examination of the supplemental indication review policy of the FDA.

Drug Evaluation↗
PubMed1989

FDA advisory committees and the new drug approval process.

To determine the impact of FDA advisory committee review on the approval time of new drug applications (NDAs) approved during the five-year period 1983 through 1987, we compared NDA phase lengths of reviewed new chemical entities (NCEs) with those that were not reviewed and examined the elapsed time from final committee recommendation for approval to NDA approval. Of the 95 drugs approved during the study period that met the Center for the Study of Drug Development's definition of an NCE, 40 (42%) were submitted for review--mean NDA phase length was 36.9 months versus 32.4 months for unreviewed drugs. Reviewed drugs in the neuropharmacologic division had a longer NDA phase, while those in the metabolic/endocrine and oncology/radiopharmaceutical divisions had shorter NDA phases, than unreviewed drugs in those divisions. For NCEs grouped by therapeutic rating, reviewed drugs in each category had longer NDA phases than unreviewed drugs; the difference was largest for 1-B rated drugs. The elapsed time from committee recommendation for approval to NDA approval as a percent of the total NDA phase was greatest for drugs submitted by the metabolic/endocrine division (83.0% of NDA phase) and for drugs rated 1-A (63.2%). Results indicate that advisory committee review is associated with a small overall delay in NDA approval when compared with the regulatory fate of drugs not submitted for review.

Drugs, Investigational↗
PubMed1989

The drug lag: an update of new drug introductions in the United States and in the United Kingdom, 1977 through 1987.

This report updates previous studies that documented the existence of a significant lag between new drug introductions in the United Kingdom and in the United States. During the 11-year period from 1977 through 1987, the United Kingdom led the United States in the number of first introductions of new drugs (114 versus 41), in average lead time for mutually available drugs (60.7 versus 28.9 months), and in the number of exclusively available drugs (70 versus 54). Analysis by therapeutic category indicated large United Kingdom leads in the introduction of respiratory (5.1 years), cardiovascular (3.2 years), central nervous system (3.2 years), and anti-cancer (2.9 years) agents, and shorter leads for anesthetic and analgesic (2.0 years), gastrointestinal (2.0 years), endocrine (1.4 years), and anti-infective (0.8 years) agents. A comparison of the 5-year period from 1983 through 1987 with the previous 5-year period (1978 through 1982) showed no change in the length of the lag time (1.9 years for each period). These results indicate that the United States continues to lag behind the United Kingdom in the availability of new drugs.

Drug Industry↗
PubMed1987

Trends in drug development: the 1985-86 new drug approvals.

New drug approvals in 1985 and 1986 were analyzed to determine whether any new trends have emerged in the US drug development process. Fifty-three new drugs (including three biologic products) were approved during this period; 46 met the Center for the Study of Drug Development's definition of a new chemical entity (NCE). More than 70% of the 46 approvals were granted in the fourth quarter, 50% in December alone. Four were FDA classified as 1A (important therapeutic gain), 24 as 1B (modest gain), and 16 as 1C (little or no gain); two biologics were not classified. Nine drugs were given orphan status. For the 37 non-orphan drugs, the duration of the "development phase" (IND filing to NDA submission) was 5.6 years; the "review phase" (NDA submission to approval) was 2.6 years; and the "total time" (IND filing to NDA approval) was 8.2 years. Review phase for the four 1A drugs was 2.4 years; for the 24 1B drugs, 2.6 years; for the 16 1C drugs, 2.8 years; and for the nine orphan drugs, 2.7 years. Of the 46 drugs, 33 (71.7%) were available in foreign markets prior to US approval with a mean of 5.5 years of prior marketing. Although the total of 46 NCE approvals in 1985 and 1986 represents a two-year high, there has been a dramatic shift towards fourth quarter approvals. Lengths of the development and FDA review phases are in keeping with those values for previous years.

Humans↗
PubMed1986

The effects of buspirone on sleep in the rat.

Buspirone is a novel anxiolytic compound that does not produce the sedation often associated with the use of benzodiazepines. The present study evaluated the effects of this anxiolytic on sleep in rats surgically prepared for long-term recordings. Buspirone, at a dose of 3 mg/kg i.p., produced a significant increase in total wake time (P less than 0.05) compared with drug-free controls. At a dose of 10 mg/kg i.p., rats displayed altered sleep patterns with the most significant effects observed in the first third of recording period. These animals displayed increased wakefulness (P less than 0.001), decreased non-REM sleep (P less than 0.001), and an obliteration of REM sleep (P less than 0.02). These data support the suggestion that the clinically useful anxiolytic buspirone, unlike the benzodiazepines, does not induce sleep.

Animals↗
PubMed1986

Sleep disturbance produced by electrical stimulation of the locus coeruleus in a human subject.

A 25-year-old man with a chronically implanted stimulating electrode placed in the region of the locus coeruleus (LC) was monitored for 5 nights in a sleep laboratory to study the role of the LC in sleep. Sleep patterns were compared between the 2 nights in which the stimulation was applied periodically every 90 min and the 2 nights in which no stimulation was applied. In contrast to the normal sleep patterns that occurred during the 2 nonstimulation nights, electrical stimulation of the LC produced a profound disruption of sleep and significant reductions in the total amounts of NREM sleep, REM sleep, REM sleep as a percent of total sleep (NREM + REM sleep), and total sleep. Results suggest that the LC has a role in maintaining normal sleep patterns.

Adult↗