Outpatient antiarrhythmic drug use from 1970 through 1986.

Antiarrhythmic drugs have been marketed in the United States for more than three decades. However, little is known about the prevalence of use of these drugs. Using data from the National Prescription Audit, we examined trends in outpatient use of oral antiarrhythmic agent types 1 and 3 from 1970 through 1986. Using the National Disease and Therapeutic Index, we assessed prescribing physician specialty and general demographic and clinical characteristics of recipients. We adjusted the numbers of prescriptions dispensed for broad changes in the US population demographics over the 17-year period. From 1970 through 1986 the number of antiarrhythmic agent prescriptions dispensed increased by 200%, from 3.8 million to 11.5 million. This increase is greater than that expected due to changes in size of the US population, estimated changes in prevalence of heart disease, or estimated changes in the proportion of patients with heart disease who have arrhythmias. The weight of evidence suggests that more persons were receiving antiarrhythmic agents in 1986 than in 1970. Physicians probably recognized and/or treated arrhythmias more frequently in 1986 than in 1970.

Trends in use of oral hypoglycemic agents 1964-1986.

Oral hypoglycemic (OH) agents have been available in the United States for the treatment of non-insulin-dependent diabetes mellitus (NIDDM) for almost 30 yr. During this time they have been subject to considerable controversy. In this article, we present pharmaceutical marketing research data that provide a review of several facets of OH use. The number of OH prescriptions dispensed peaked in 1973, decreased through 1980, and has been increasing since that year. In 1986, OH agents accounted for 21.5 million prescriptions: 1% of all prescriptions dispensed that year. Chlorpropamide is currently the most frequently ingested OH agent; it is used by 33% of the market. The two OH agents introduced in 1984, glyburide and glipizide, had acquired 41% of the OH market by the end of 1986. The rate of OH use per 1000 diabetes mellitus visits increases with patient's age. Patients aged 60 yr and older received OH prescriptions at a rate of 478 per 1000 diabetes mellitus visits in 1986. Data estimating both the number of patients diagnosed with diabetes and the number of diabetic patients taking OH agents indicate that the percentage receiving OH treatment has increased over the past 5 yr, with approximately 35% of all diabetic patients taking OH agents in 1986.

Drug therapy for ambulatory pediatric patients in 1979.

Little data are available on the use of drugs in children on an outpatient basis. Therefore, the present study investigated national patterns in the prescribing of drugs for children by office-based physicians during 1979, in order to describe the most commonly encountered pediatric drug therapies. The data are presented as descriptive norms of drug therapy by office-based physicians in two pediatric subgroups, 0 to 2 years old and 3 to 9 years old. Anti-infective drugs and cough and cold preparations accounted for approximately 50% of drugs used. Tetracycline and its congeners continue to be used in pediatric patients. Despite apparent advantages of amoxicillin, ampicillin is still widely used.

National patterns of aspirin use and Reye syndrome reporting, United States, 1980 to 1985.

The number of cases of Reye syndrome reported annually to the Centers for Disease Control declined markedly between 1980 and 1985. In this article, we present pharmaceutical marketing research data that suggest sharp decreases in the use and purchase of children's aspirin between 1980 and 1985. These trends appear to correspond to the decrease in reporting of Reye syndrome cases. Additionally, analysis of physician mentions of aspiring and acetaminophen for treating flu and chickenpox showed statistically significant trends toward decreasing recommendations for the use of aspirin and significant trends toward increasing recommendations for use of acetaminophen. Trends in wholesale purchases of aspirin and acetaminophen by drug stores from 1979 through 1985 demonstrated a significant decline for the 81-mg children's aspirin tablet and an increase in purchases of children's acetaminophen products. Many factors may influence physician and parents' choice of analgesic/antipyretic medication, including information about Reye syndrome. Data suggest that a continuing decline in the use of aspirin for children may be accompanied by a continuing decline in the reported number of Reye syndrome cases.

Oral contraceptives in the United States: trends in content and potency.

Data from the National Prescription Audit, a nationwide pharmaceutical marketing research data base, were reviewed to study changes in the type of oral contraceptives marketed in the US, their content and their relative oestrogen and progestin potency over the 21-year time period of 1964-84. Three major types and 42 brands of oral contraceptives were marketed in the US during this time period. All oral contraceptives dispensed in the US have contained one of nine different progestins and one of two oestrogens or, in the case of the progestin-only pills, no oestrogen at all. A comprehensive classification listing all 42 brands of oral contraceptives by content and strength is presented. Secular changes in oral contraceptive potency are described in terms of a categorization scheme which simultaneously ranks both the oestrogen and progestin potencies of each oral contraceptive. Over the time period studied, oral contraceptives have evolved from high strength, high potency drugs to much lower strength, lower potency drugs. The epidemiological implications of these shifts in oral contraceptive content and potency are discussed.

Oral contraceptive oestrogen and progestin potencies and the incidence of deep venous thromboembolism.

To assess possible differences in the incidence of venous thrombosis and pulmonary embolism associated with oral contraceptives of varying hormonal potencies, the authors conducted a retrospective cohort study in the 15-44 year old Michigan Medicaid population. Cohorts were defined by the progestin- and oestrogen-potencies of oral contraceptives in use at the time of follow-up as classified by an oral contraceptive potency scheme. Using the low-oestrogen-/low-progestin-potency formulations for reference (rate ratio = 1), adjusted rate ratios of 0.8 (95% CI: 0.5 to 1.3, P = 0.41) and 0.6 (95% CI 0.4 to 1.2, P = 0.13) were observed for intermediate-progestin-potency and high-progestin-potency formulations, respectively. Adjusted rate ratios of 1.4 (95% CI: 0.8 to 2.3, P = 0.21) and 2.6 (95% CI: 1.2 to 5.5, P = 0.01) were observed for intermediate- and high-oestrogen-potency formulations. These data suggest a dose-response relationship between oral contraceptive oestrogen potency and venous thromboembolism, whereas no such evidence for a dose-response relationship between oral contraceptive progestin potency and venous thrombo-embolism was found.

Noncontraceptive estrogens and progestins: use patterns over time.

The use of noncontraceptive estrogens and progestins, particularly in menopausal women, has been a subject of considerable controversy during the past decade. Reported is a review of overall trends in the use of these drugs from 1966 to 1983 and a more indepth qualitative and quantitative description of their use during 1983. The use of these estrogens and progestins appears to be increasing again. The estrogens are apparently being used at lower doses than in the past, and there is a trend toward using estrogens and progestins concomitantly. Exclusive of oral contraceptives, enough oral estrogen was purchased during 1983 to treat an average of 2.3 million people each day, while oral progestin purchases could have supplied 129,000 people daily.

Thyroid hormone use: trends in the United States from 1960 through 1988.

Thyroid hormone preparations comprised over 1% of all prescriptions filled by retail pharmacies during 1988 in the conterminous United States, i.e., the 48 contiguous states. Their large market share gives the patterns of their use substantial public health importance. This article describes prescription thyroid hormone use in the United States from 1960 through 1988, using pharmaceutical marketing research data collected from panels of retail pharmacies and office-based physicians. Although the use of natural products has declined by over 50% since 1960, about one fourth of all thyroid hormone prescriptions were for natural preparations as recently as 1988. Per capita thyroid mentions (i.e., patient-physician contacts during which a thyroid agent of any kind was recommended, prescribed, dispensed, administered, ordered to be given by a hospital, or given as a sample) doubled during this period among those over 59 years old. Per capita mentions for synthetic thyroid products increased fourfold and tenfold among men and women in this age group, respectively. Use for weight loss, despite the label's boxed warning indicating it to be ineffective and potentially dangerous, has diminished but persists. Obesity was second only to hypothyroidism among the diagnoses underlying thyroid product mentions.

Reporting of adverse events to MedWatch.

Trends in the reporting of serious adverse events directly to FDA between 1992 and 1994 and the quality of reports before and after the June 1993 launching of MedWatch were studied. Computerized data were used to assess changes between 1992 and 1994 in the proportion of adverse-event reports to FDA classified as serious. To evaluate the quality of reports, every third report received during April 1993 (sample size, 254) and April 1994 (263) was evaluated for 21 variables and to determine whether the event was serious. For the first analysis, a serious adverse event was defined as one that resulted in death, hospitalization or prolongation of hospitalization, or disability; for the second, the outcome of a threat to life was also included. The proportion of reports that were serious increased from 34% in 1992 to 49% in 1994. The overall quality of the reports made in 1994 was higher than that of the 1993 reports. In particular, significantly higher percentages of reports in 1994 indicated whether the drug was a new molecular entity, indicated whether the event was serious, and gave laboratory and clinical information in support of the event diagnosis. Reports from pharmacists increased both in number and in quality. Physicians' reports were of high quality in both years, but the number of reports they made decreased. The proportion of adverse-event reports classified as serious increased between 1992 and 1994, and the quality of event reporting to FDA improved since the introduction of MedWatch.

The use of patient-reported outcome measures in the evaluation of medical products for regulatory approval.

Patient-reported outcome (PRO) measures provide an important perspective on how patients feel and function that cannot be adequately captured by clinical measures. A PRO is any report that comes directly from a patient about a health condition or its treatment without interpretation of the patient's response by a clinician or anyone else.

Behavior of alcoholics and spouses in a simulation game situation.

The interaction of alcoholics and their spouses in a simulation game was systematically observed and compared to the behavior of nonalcoholic couples. Overall, 28 couples played a mixed-motive bargaining game, the "tax game," which is a modification of Kelly's "game of nines." Alcohol couples as a group did not manifest a distinct game "style." They were less uniform in this respect than "normal" couples and a mixed group of "psychiatrically disturbed" couples. Subgroup trends without the alcoholic sample were suggested and discussed. Extreme behavior, rigidity, and lack of communication were common features in the game behavior of alcoholic couples that did not appear to relate to a particular game style, but did distinguish the game play of alcoholic couples from that of nonalcoholic couples.

Data sources and methods for ascertaining human exposure to drugs.

Estimates of population exposure based on drug use data are critical elements in the post marketing surveillance of drugs and provide a context for assessing the various risks and benefits associated with drug treatment. Such information is important in predicting morbidity and planning public health protection strategies, indepth studies, and regulatory actions. Knowledge that a population of one thousand instead of one million may potentially be exposed to a drug can help determine how a particular regulatory problem will be handled and would obviously be a major determinant in designing a case-control or cohort study. National estimates of drug use give an overview of the most commonly used drug therapies in current practice. They also furnish valuable comparison data for specific studies of drug use limited to one group of drugs, one geographic region, or one medical care setting. The FDA has access to several different national drug use data bases, each measuring a different point in the drug distribution channels. None covers the entire spectrum of drug exposures. The major "holes" in this patchwork of data bases are the inability to measure OTC drug use with any accuracy and the lack of qualitative information on drug use in hospitals. In addition, there is no patient linkage with the data. The data can only show trends in drug use. They impart no sense of the longitudinal use of drugs for individual patients. There is no direct connection between the different data bases, all of which have their own sampling frames and their own projection methodologies. The market research companies have complete control over these methodologies and they are subject to periodic changes, a situation not entirely satisfactory for epidemiologic research. Sometimes it is a struggle to keep up with these changes. Over the past two years, every one of these data bases has undergone some type of sampling or projection methodology change. One important limitation to the use of all of these data bases is that they are subscription data bases, that is, the FDA purchases the data under contract to the marketing research companies and by doing so assumes certain contract obligations. Anytime the FDA wants to release any data outside of the Agency, it must first notify the company in sufficient time for review and approval. Subscribing to these data bases is costly, but the subscription cost is insignificant, compared to the estimated cost of duplicating these services. In spite of all of the limitations of these systems, there are obvious advantages.(ABSTRACT TRUNCATED AT 400 WORDS)

Prescription drug use before and during pregnancy in a Medicaid population.

This study describes prescription drug use before and during pregnancy and is based on data obtained from the paid Medicaid claims of 18,886 Michigan women aged 15 to 44 years who were delivered of a live infant. Rates of exposure to drugs within 15 therapeutic categories are presented for each of five 90-day periods preceding delivery. Overall dispensed drug use (excluding vitamins) decreased during pregnancy; however, there was still substantial exposure to drugs including drugs that are contraindicated during pregnancy. During the gestational period, study mothers received an average of 3.1 prescriptions for nonvitamin drugs. Black mothers received more exposure to drugs other than vitamins than did white mothers. Black mothers had higher rates of exposure to analgesics, ampicillin, codeine, and vaginal preparations. Similarities between black and white mothers in the use of vitamins with and without other drugs suggest there is no racial difference in attaining prenatal care within the Medicaid system, but that black mothers may have more medical problems that warrant the use of other medications in addition to vitamins during pregnancy.

Predominant integration end products of infecting bacteriophage Mu DNA are simple insertions with no preference for integration of either Mu DNA strand.

The integration of 32P-labeled infecting Mu DNA into the Escherichia coli chromosome was investigated. Cleavage of the integrated Mu DNA with restriction endonuclease EcoRI, which cuts twice in the Mu genome, liberated the internal EcoRI fragment but not the left and right end fragments. The ends of the Mu genome became fused with host DNA at a variety of locations generating a smear of radioactive DNA fragments following cleavage with EcoRI. The predominant integration end products of infecting Mu DNA molecules are therefore generated by a mechanism which results in simple insertions and not cointegrates. Since predominantly simple insertions are found after infection (during lysogenization or lytic growth) but not after prophage induction, the transposition mode which is utilized appears to be a function of the source of the transposing DNA. Use of the integrated, 32P-labeled Mu DNA as a hybridization probe with the separated strands of Mu DNA or lambda phages carrying various regions of Mu showed no strand preference in the integration process. Both labeled DNA strands at both ends of the Mu genome were integrated. These results suggest the lack of a site-specific recombination site in the genome; the simple insertions which are the end products of Mu DNA integration following infection appear to be generated by a separate pathway rather than by the resolution of cointegrate structures.

Prescribed use of cholesterol-lowering drugs in the United States, 1978 through 1988.

Data from two pharmaceutical marketing research databases, the National Prescription Audit and the National Disease and Therapeutic Index, were used to study trends in outpatient use of cholesterol-lowering drugs in the United States from 1978 through 1988. Retail pharmacies dispensed an estimated 4.4 million prescriptions for cholesterol-lowering drugs in 1978. This declined to 2.6 million in 1983 and increased dramatically to nearly 13 million in 1988. This fivefold increase between 1983 and 1988 was accounted for primarily by the introduction and use of two new drugs, gemfibrozil and lovastatin, and, to a lesser extent, by the increasing use of some older drugs. In 1988, after 1 full year of marketing, lovastatin was the leading cholesterol-lowering drug, followed closely by gemfibrozil; both drugs are currently considered second-line agents. Clofibrate and dextrothyroxine, drugs that ranked first and second in 1978, declined to ranks of sixth and eighth out of eight in 1988. Cholestyramine, gemfibrozil, and lovastatin accounted for about 75% of all lipid-lowering prescriptions in 1988. From 1978 through 1988, an average 54% of individuals using cholesterol-lowering drugs were 60 years of age or older. The 13 million prescriptions for cholesterol-lowering drugs in 1988 represent a maximum estimate of 13 million treated individuals. This number compares with the 60 million Americans with high cholesterol levels who are candidates for dietary advice, and, if cholesterol levels do not improve, for combined diet and drug intervention.

Use and reported adverse effects of new chemical entities.

Reports submitted to the FDA through 1987 of adverse drug reactions (ADRs) to new chemical entities (NCEs) approved after 1983 are described, and estimates of each NCE's proportionate use in hospitals and within its therapeutic class are reported. This review was limited to those domestic spontaneous ADR reports submitted to the FDA by healthcare professionals. NCEs accounted for approximately 20% of the total number of domestic spontaneous ADR reports received in 1987, 22% of the reports of serious ADRs, and 24% of the reports that listed death as an outcome. Data on the use of these NCEs were obtained through the U.S. Pharmaceutical Market--Drugstores and Hospitals and the National Prescription Audit. Of the 93 drugs designated as NCEs in 1987, 65 had measurable use, with 41% of those used principally in hospitals. Most hospital-use NCEs were injectable antimicrobial agents, surgical drugs, and radioactive diagnostic agents. Because NCEs account for a disproportionate share of the ADRs reported to the FDA, and because of the high use of NCEs in hospitals, hospital pharmacists should be aware of the importance of monitoring and reporting serious ADRs associated with NCEs.

Utilization of nonsteroidal antiinflammatory drugs.

Information derived from pharmaceutical marketing databases on the use of 12 nonsteroidal antiinflammatory drugs in 1983 is presented. Estimates of population exposure, regularity of treatment, average daily dose, age and sex distributions of users, concomitant use of other drugs, associated diagnoses, and trends in use are provided. Utilization patterns were similar for 8 of the nonsteroidal antiinflammatory drugs, with differing patterns seen for mefenamic acid, oxyphenbutazone, phenylbutazone, and zomepirac.