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.

Improving patient care by reporting problems with medical devices.

Healthcare practitioners are the primary users of medical devices for direct patient care. As such, they are in the best position to recognize problems that result from the use of medical devices. The outcome of a device-related adverse event or product problem, as with any other medical product, can be serious and result in illness injury, or even death. The sooner that FDA learns about a problem, the sooner the agency can take action to protect patient and user safety. Healthcare practitioners are major contributors to the knowledge base related to device use and safety through astute monitoring, rapid identification of device-related problems, and reporting these problems. An understanding of the voluntary and mandatory mechanism of reporting will ensure that device problems are reported appropriately and in a timely manner. As the primary users of medical equipment for direct patient care, health care professionals have the training and expertise to improve patient care by reporting actual and suspected problems with medical devices.

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.

Capability of hospital computer systems in performing drug-use evaluations and adverse drug event monitoring.

A survey to determine the extent of computerization in key areas of hospitals, the information being collected in the databases, and the capabilities of the computer systems for performing adverse drug event monitoring and drug-use evaluations was conducted. The questionnaire was distributed to clinical pharmacists in the 500 hospitals composing the Drug Surveillance Network. In the majority of the 166 responding hospitals (> 85%), the pharmacy department, clinical chemistry and hematology laboratories, patient admissions, and microbiology laboratory were computerized for data acquisition and management. The medical records and purchasing departments were computerized in a smaller proportion of hospitals (75% and 74%, respectively). In the majority of hospitals with a computerized pharmacy department (> 78%), there was ready access to computer databases in other departments, but simultaneous querying of multiple databases was possible in only 30%. Patients could be identified according to diagnosis in 82% of the hospitals and according to medication received in 83%. More than 85% of responding hospitals had implemented spontaneous reporting systems for the identification of adverse drug events. Computers are widely used in hospitals participating in the Drug Surveillance Network, but a substantial effort is necessary to make these resources more useful and to standardize processes so that data may be pooled across institutions to deal with important public health concerns.

Medications and the safety of the older driver: is there a basis for concern?

Medications with central nervous system (CNS) effects, including benzodiazepines, cyclic antidepressants, antihistamines, narcotic analgesics, and hypoglycemics, have been thought to have the potential to impair driving. These drugs impair performance in younger drivers and some have been linked to an increased risk of motor vehicle crashes. Even though persons 65 years of age and older frequently take these drugs and are more susceptible to CNS effects, no direct data exist regarding whether or not medications adversely affect driving safety in this population. Thus there is an urgent need for further research in this area.

Trends in the content and use of oral contraceptives in the United States, 1964-88.

Drug marketing and physician survey data were used to examine trends in the use and hormonal content of oral contraceptives in the United States between 1964 and 1988. Retail prescriptions for oral contraceptives peaked at approximately 68 million in 1973 and have remained between 50 million and 60 million since 1981. Despite this relative consistency in the number of prescriptions, physician "mentions" of oral contraceptives have increased by approximately 75 percent. This increase may reflect closer monitoring of women on oral contraceptives. Use of multiphasic formulations has steadily risen, accounting for 37 percent of the oral contraceptive prescriptions in 1988. Mean estrogen and progestin doses in all types of formulations have steadily declined. A change in the type of estrogen and progestin used in preparations has coincided with this decline in dose. The association between age and use of high-dose formulations seen in the past was no longer evident in 1988. The data demonstrate that oral contraceptive formulations in wide use today differ in hormone content from those of the past, when most of the major studies addressing the risks associated with oral contraceptive use were completed. There is therefore a need to determine the risks and long-term effects associated with these newer formulations.

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.

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.

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.

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.

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.

Prescribing of noncontraceptive estrogens and progestins in the United States, 1974-86.

This paper describes changes in the prescribing of noncontraceptive estrogens and progestins, using data from pharmaceutical marketing surveys. The number of estrogen prescriptions decreased from 1975 to 1980, and then increased through 1986. Progestin use has increased since 1982; concomitant use of estrogens and progestins increased over time and was common in 1986. The trends suggest that the use of estrogens, particularly the combined use of estrogens and progestins, will continue to increase.