Oral almotriptan vs. oral sumatriptan in the abortive treatment of migraine: a double-blind, randomized, parallel-group, optimum-dose comparison.

BACKGROUND: Almotriptan malate is a novel, selective serotonin(1B/D) agonist, or triptan, developed for the abortive treatment of migraine. In double-blind, placebo-controlled studies, it has been shown to be effective, well tolerated, and safe. OBJECTIVE: To compare the efficacy, tolerability, and safety of almotriptan with that of the "standard triptan," sumatriptan succinate. The power calculation of the study was based on 24-hour headache recurrence, an efficacy measure in the abortive treatment of migraine, and on the occurrence of adverse events. SUBJECTS AND METHODS: Subjects, aged between18 and 65 years, with migraine with or without aura but otherwise healthy, were randomized to take orally either almotriptan malate, 12.5 mg, or sumatriptan succinate, 50 mg. The medications were provided in identical-looking capsules to ensure blinding and were taken for the treatment of moderate or severe headache. Efficacy was determined in terms of (1) headache relief-a decrease in pain intensity to mild or no pain; (2) headache freedom-a decrease to no pain; (3) use of rescue medications, allowed after 2 hours; and (4) headache recurrence-moderate or severe pain returning within 24 hours after headache relief at 2 hours. Adverse events were collected for 96 hours after treatment and for safety evaluation, vital signs, blood tests, and electrocardiograms were performed at the screening and exit visits. RESULTS: Seventy-five investigators enrolled 1255 subjects of whom 1173 were treated (591 with almotriptan and 582 with sumatriptan). At 2 hours, almotriptan treatment provided headache relief in 58.0% of the subjects and sumatriptan treatment in 57.3%; headache freedom was provided by the medications in 17.9% and 24.6%, respectively (P =.005). Rescue medications were taken by 36.7% of the subjects in the almotriptan-treated group and by 33.2% in the sumatriptan-treated group; headaches returned to moderate or severe intensity in 27.4% and 24.0%, respectively. Treatment-emergent adverse events occurred in 15.2% of the subjects in the almotriptan-treated group and in 19.4% in the sumatriptan-treated group (P =.06); treatment-related adverse events occurred in 9.1% and 15.5% of the subjects, respectively (P =.001), including chest pain, which occurred in 0.3% and 2.2%, respectively (P =.004). CONCLUSIONS: Almotriptan and sumatriptan are similarly effective in the abortive treatment of moderate or severe migraine headache; they are also similarly well tolerated and safe.

Multicenter, phase II trial of exemestane as third-line hormonal therapy of postmenopausal women with metastatic breast cancer. Aromasin Study Group.

PURPOSE: To assess the antitumor activity, safety, and hormone-suppressive effects of the irreversible aromatase inactivator, exemestane (Aromasin, Pharmacia & Upjohn, Kalamazoo, MI), administered as third-line hormone therapy to postmenopausal women with metastatic breast cancer that is refractory to tamoxifen and megestrol acetate. PATIENTS AND METHODS: Exemestane was administered at a dose of 25 mg/d orally until patients experienced disease progression. The efficacy and safety of exemestane were clinically and radiographically evaluated. The impact of exemestane treatment on tumor-related signs and symptoms was assessed. The effect of exemestane on serum levels of estrogens and other steroidal hormones was determined. RESULTS: Ninety-one patients were treated. There were four complete responses (CR) and eight partial responses (PR), for an objective response rate of 13% in the entire treated population. The overall success rate (CR, PR, or stable disease [SD] >/= 24 weeks) was 30%. The median duration of response and overall success was 9 months and 8 months, respectively. Most patients with CR/PR (83%; 10 of 12 patients) and SD >/= 24 weeks (80%; 12 of 15 patients) had improved or stable tumor-related signs and symptoms. Mean levels of circulating estrone (E(1)), estradiol (E(2)), and estrone sulfate decreased to 11%, 22%, and 13% of baseline levels, respectively (at week 8 or 16 of treatment). One half of the patients had undetectable E(1) and E(2) levels during treatment, including at the time of disease progression. Mild nausea (20% of patients) and hot flashes (20%) were the most common drug-related adverse events and were generally grade 1. CONCLUSION: Exemestane is an active and well-tolerated third-line hormonal therapy that represents a new treatment option for postmenopausal patients with advanced breast cancer that has become refractory to standard first- and second-line hormonal therapies.

A phase I and pharmacokinetic study of tallimustine [PNU 152241 (FCE 24517)] in patients with advanced cancer.

Tallimustine [PNU 152241 (FCE 24517)] is a synthetic derivative of the DNA minor groove binder distamycin A, in which the NH2-terminal formyl group is substituted by benzoyl mustard. In this Phase I clinical trial, patients with advanced solid tumors received i.v. bolus injections of tallimustine daily for 3 consecutive days. Patients were treated at six dosage levels of 33.3 micrograms/m2/day to 250 micrograms/m2/day for 3 consecutive days, with courses of therapy repeated every 28 days. Detailed pharmacokinetic blood sampling was performed during the first 3 days of the first course of tallimustine. The plasma samples were analyzed by high-performance liquid chromatography with UV detection. Forty-eight eligible patients were treated at all six dosage levels. The dominant dose-related toxicity of tallimustine was neutropenia, becoming dose limiting at 250 micrograms/m2/day. At this dosage level, one patient experienced febrile neutropenia, and a second patient died on study of indeterminate cause. Thrombocytopenia was not observed, and only 10 patients developed anemia < 8.0 gm/dl. Sporadic elevation of liver enzymes or bilirubin was observed but was not dose related. Pharmacokinetic analysis gave reliable results for 33 patients. For most patients, analysis of the data best fit a three-exponential model. Dose-related increases in areas under the concentration-time curve and end-of-infusion concentrations were observed. There was no significant plasma accumulation of tallimustine over the 3 days of administration. The terminal half-life of tallimustine in individual patients ranged from 6.83 to 39.02 h following the last dose. In summary, the recommended Phase II dosage for tallimustine is 200 micrograms/m2/day for 3 consecutive days every 28 days. Neutropenia is the principal toxicity of this agent at this dosage and schedule.

Long-term follow-up of three randomized trials comparing idarubicin and daunorubicin as induction therapies for patients with untreated acute myeloid leukemia.

BACKGROUND: Most clinical trials for acute leukemia have reported results after 2-3 years of follow-up. Comparisons between the original data and longer-term follow-up data may be of interest, particularly with regard to promising new therapies. METHODS: In 1996, survival data were updated from three prospective, randomized comparisons of idarubicin and daunorubicin that began in 1984 and 1985. These were trials of the Memorial Sloan-Kettering Cancer Center (MSKCC), the U.S. Multicenter Study Group, and the Southeastern Cancer Study Group (SEG). The original results of these trials were reported in 1991 and 1992. RESULTS: The original results of the SEG trial demonstrated no significant difference between idarubicin and daunorubicin. The updated survival analysis showed similar results. The MSKCC trial revealed a significant advantage of idarubicin compared with daunorubicin in both the original and the updated analyses. The U.S. Multicenter trial found a significant difference favoring idarubicin in the original analysis, but the difference was not significant in the updated analysis. CONCLUSIONS: It is essential that the median length of follow-up be clearly stated in any clinical trial. When the results obtained with a particularly promising new drug or procedure are presented early in the course of study (within 1-2 years), the investigators should strongly consider a repeat evaluation after an additional 3-5 years of follow-up.

Cardioprotection with dexrazoxane for doxorubicin-containing therapy in advanced breast cancer.

PURPOSE: To determine the cardioprotective effect of dexrazoxane (DZR) used in a doxorubicin-based combination therapy in advanced breast cancer. PATIENTS AND METHODS: Between November 1988 and January 1991, 534 patients with advanced breast cancer were randomized to two multicenter, double-blind studies (088001 and 088006). Patients received fluorouracil, doxorubicin, and cyclophosphamide (FAC) with either DZR (DZR-to-doxorubicin ratio, 10:1) or placebo (PLA) every 3 weeks and were monitored with serial multiplegated acquisition (MUGA) scans. RESULTS: The hazards ratio (HR) of PLA to DZR for a cardiac event, which was predefined ejection fraction changes or congestive heart failure (CHF), was 2.63 (95% confidence interval [CI], 1.61 to 4.27; P < .001) for 088001 and 2.00 (95% CI, 1.01 to 3.96; P = .038) for 088006. The objective response rates for 088001 were 46.8% for DZR and 60.5% for PLA, a difference of 14% (95% CI, -25% to -2%; P = .019), and for 088006 were 53.7% for DZR and 49.3% for PLA, a difference of 4% (95% CI, -13% to 22%; P = .63). Time to progression and survival were not significantly different between treatment arms in either study. Toxicities on the DZR arms included lower granulocyte and platelet counts at nadir (P = .009 and P = .004, respectively) and more pain on injection (P = .001), with no difference in the rates of fever, infection, or hemorrhage. CONCLUSION: DZR had a significant cardioprotective effect as measured by noninvasive testing and clinical CHF. One of the two studies (088001) showed a lower response rate with DZR, but time to progression and survival were not significantly different. DZR is the first agent shown to reduce cardiotoxicity from doxorubicin.

Delayed administration of dexrazoxane provides cardioprotection for patients with advanced breast cancer treated with doxorubicin-containing therapy.

PURPOSE: To assess whether dexrazoxane (DZR) given after a cumulative doxorubicin dose of 300 mg/m2 confers cardioprotection in patients with advanced breast cancer treated with fluorouracil, doxorubicin, and cyclophosphamide (FAC). PATIENTS AND METHODS: In two multicenter studies (088001 and 088006), patients were randomized to receive FAC and placebo (PLA) versus FAC and DZR. After a protocol amendment, all patients received open-label DZR after they had reached a cumulative doxorubicin dose of 300 mg/m2. Two groups were compared: 99 patients randomized to the PLA arms before the amendment who received FAC and PLA for at least seven courses (PLA group), and 102 patients randomized to the PLA arms after the amendment who received FAC and PLA for six courses followed by open-label DZR (PLA/DZR group). RESULTS: The hazards ratio of PLA to PLA/DZR was 3.5 (95% confidence interval [CI], 2.2 to 5.7; P < .001, logrank and generalized Wilcoxon tests) for the doxorubicin dose at any cardiac event, ejection fraction changes, or congestive heart failure (CHF). The hazards ratio of PLA to PLA/DZR was 13.1 (95% CI, 3.7 to 46.0; P < .001, logrank and generalized Wilcoxon tests) for the doxorubicin dose at the development of CHF. The overall incidence of CHF in the PLA/DZR group was 3%, compared with 22% in the PLA group (P < .001, Fisher's exact test). Twenty-six percent of PLA/DZR patients received at least 15 courses of therapy, compared with 5% of patients in the PLA group. These results do not appear to be attributable to a time trend. CONCLUSION: DZR is a highly effective cardioprotective agent when used in patients with advanced breast cancer who continue to receive doxorubicin-based chemotherapy after a cumulative doxorubicin dose of 300 mg/m2 has been reached.

Clinical utility of external immunoscintigraphy with the IMMU-4 technetium-99m Fab' antibody fragment in patients undergoing surgery for carcinoma of the colon and rectum: results of a pivotal, phase III trial. The Immunomedics Study Group.

PURPOSE: To assess the performance and the potential clinical impact of a new antibody imaging agent, CEA-Scan (Immunomedics Inc, Morris Plains, NJ), in 210 presurgical patients with advanced recurrent or metastatic colorectal carcinomas. METHODS: CEA-Scan, an anti-carcinoembryonic antigen (CEA) Fab antibody fragment labeled with technetium-99m-pertechnetate (99mTc), was injected intravenously (IV), and external scintigraphy was performed 2 to 5 and 18 to 24 hours later. Imaging with conventional diagnostic modalities (CDM) was also performed, and findings were confirmed by surgery and histology. RESULTS: The sensitivity of CEA-Scan was superior to that of CDM in the extrahepatic abdomen (55% v 32%; P = .007) and pelvis (69% v 48%; P = .005), and CEA-Scan findings complemented those of CDM in the liver. Among 122 patients with known disease, the positive predictive value was significantly higher when both modalities were positive (98%) compared with each alone (68% to 70%), potentially obviating the need for histologic confirmation when both tests are positive. Imaging accuracy also was significantly improved by adding CEA-Scan to CDM. In 88 patients with occult cancer, imaging accuracy was enhanced significantly by CEA-Scan combined with CDM (61% v 33%). Potential clinical benefit from CEA-Scan was demonstrated in 89 of 210 patients. Only two patients developed human antimouse antibodies (HAMA) to CEA-Scan after a single injection, and none of 19 assessable patients after two injections. CONCLUSION: CEA-Scan affords high-quality, same-day imaging, uses an inexpensive and readily available radio-nuclide, adds clinically significant information in assessing extent and location of disease in colorectal cancer patients, and only rarely induces a HAMA response.

Drug use prevalence in a rural school-age population: the New Hampshire survey.

Pre-adolescent and adolescent drug use is a major public health concern in the United States. Although we have good prevalence data on some adolescents, we have little information on pre-adolescents, young adolescents, and rural children. We conducted a survey of 4,406 children in grades 4-12 in rural New Hampshire in 1990. Students completed annual self-report surveys on demographic characteristics, drug use, and psychosocial risk factors. These children are initiating drug use in elementary school. Alcohol is the preferred drug for both genders at all grade levels, followed by cigarettes, marijuana, and spitting tobacco. Current use of these drugs escalates in the sixth through ninth grades. Lifetime prevalence and 30-day prevalence increase slowly through high school. Most children who are going to use drugs have begun by the tenth grade. In this rural state, children's drug preferences are similar to those of other pre-adolescents and adolescents. Rural students have equal, and in some cases higher, lifetime and current use prevalence of alcohol, marijuana, and tobacco in comparison with national samples.

Telephone care as a substitute for routine clinic follow-up.

DESIGN: Randomized trial. SETTING: A primary care clinic. PATIENTS: Four hundred ninety-seven men aged 54 years or older. OBJECTIVE: We examined the hypothesis that substituting clinician-initiated telephone calls (telephone care) for some clinic visits would reduce medical care utilization without adversely affecting patient health. INTERVENTION: Clinicians were asked to double their recommended interval for face-to-face follow-up and schedule three intervening telephone contacts; for control patients, the follow-up interval recommended by their clinician was unchanged. MAIN OUTCOME MEASURES: Use of medical services and health status. RESULTS: During the 2-year follow-up period, 7% of patients withdrew or became unavailable. Telephone-care patients had fewer total clinic visits, scheduled and unscheduled, than usual-care patients (19%, P less than .001). In addition, telephone-care patients had less medication use (14%, P = .006), fewer admissions, and shorter stays in the hospital (28% fewer total hospital days, P = .005), and 41% fewer intensive care unit days (P = .03). Estimated total expenditures for telephone care were 28% less per patient for the 2 years ($1656, P = .004). For the subgroup of patients with fair or poor overall health at the beginning of the study (n = 180), savings were somewhat greater ($1976, P = .01). In this subgroup, improvement in physical function from baseline (P = .02) and a possible reduction in mortality (P = .06) were also observed. CONCLUSION: We conclude that substituting telephone care for selected clinic visits significantly reduces utilization of medical services. For more severely ill patients, the increased contact made possible by telephone care may also improve health status and reduce mortality.

Cancer: improving early detection and prevention. A community practice randomised trial.

OBJECTIVE: To test the impact of physician education and facilitator assisted office system interventions on cancer early detection and preventive services. DESIGN: A randomised trial of two interventions alone and in combination. SETTING AND SUBJECTS: Physicians in 98 ambulatory care practices in the United States. INTERVENTIONS: The education intervention consisted of a day long physician meeting directed at improving knowledge, attitudes, and skills relevant to cancer prevention and early detection. The office system intervention consisted of assistance from a project facilitator in establishing routines for providing needed services. These routines included division of responsibilities for providing services among physicians and their staff and the use of medical record flow sheets. MAIN OUTCOME MEASURES: The proportions of patients provided the cancer prevention and early detection services indicated annually according to the US National Cancer Institute. RESULTS: Based on cross sectional patient surveys, the office system intervention was associated with an increase in mammography, the recommendation to do breast self examination, clinical breast examination, faecal occult blood testing, advice to quit smoking, and the recommendation to decrease dietary fat. Education was associated only with an increase in mammography. Record review for a patient cohort confirmed cross sectional survey findings regarding the office system for mammography and faecal occult blood testing. CONCLUSION: Community practices assisted by a facilitator in the development and implementation of an office system can substantially improve provision of cancer early detection and preventive services.

The accuracy of Medicare's hospital claims data: progress has been made, but problems remain.

BACKGROUND: Health care databases provide a widely used source of data for health care research, but their accuracy remains uncertain. We analyzed data from the 1985 National DRG Validation Study, which carefully reabstracted and reassigned ICD-9-CM diagnosis and procedure codes from a national sample of 7050 medical records, to determine whether coding accuracy had improved since the Institute of Medicine studies of the 1970s and to assess the current coding accuracy of specific diagnoses and procedures. METHODS: We defined agreement as the proportion of all reabstracted records that had the same principal diagnosis or procedure coded on both the original (hospital) record and on the reabstracted record. We also evaluated coding accuracy in 1985 using the concepts of diagnostic test evaluation. RESULTS: Overall, the percentage of agreement between the principal diagnosis on the reabstracted record and the original hospital record, when analyzed at the third digit, improved from 73.2% in 1977 to 78.2% in 1985. However, analysis of the 1985 data demonstrated that the accuracy of diagnosis and procedure coding varies substantially across conditions. CONCLUSIONS: Although some diagnoses and all major surgical procedures that we examined were accurately coded, the variability in the accuracy of diagnosis coding poses a problem that must be overcome if claims-based research is to achieve its full potential.

Comparison of different maximum likelihood estimators in a small sample logistic regression with two independent binary variables.

In order to examine the bias of the estimate of the log odds ratio in a 2 x 2 contingency table, Walter computed the entire distribution of the estimated log odds ratio using various small sample sizes. This is equivalent to computing the distribution of the estimated parameter b1 in a logistic regression with one independent binary variable. In this paper, the distributions of the estimated parameters b1 and b2 for two independent binary variables are computed for some small sample logistic regressions using six different estimation methods based on maximum likelihood. These estimates are then compared to the true parameter values. The best estimation method depends on the frequency of the outcome of interest and on whether the bias or mean square error is considered more important.

Hip fracture incidence and mortality in New England.

We used Medicare data to conduct a population-based study of osteoporotic hip fracture incidence and outcomes among New England residents. To reduce bias and improve data reliability, we combined data from multiple files; we found that 6% of cases would have been missed had we relied on hospital claims alone. Hip fracture incidence (per 1,000 person-years) increased for white females from 2.2 for ages 65-69 to 31.8 for ages 90-94 and for white males from 0.9 for ages 65-69 to 20.8 for ages 90-94. Incidence among blacks was lower in all age/sex groups. The female/male relative risk was greater among whites than among blacks. Case fatality following hip fracture was 12.5% at 90 days and 23.7% at 1 year and was higher among males, older patients, and those who had documented comorbidity or who were residents of nursing homes.

Further study of the increased mortality following transurethral prostatectomy: a chart-based analysis.

Previous studies using large administrative databases found an elevated relative risk of reoperation and death after transurethral resection of the prostate compared to open prostatectomy. To investigate whether differences in case-mix unmeasured by administrative data explained this finding, we reviewed the charts of 485 patients who had undergone prostatectomy (236 open and 249 transurethral) at the Health Science Centre, Winnipeg, Manitoba, Canada between 1974 and 1980. Data from patient histories, physical examinations and laboratory evaluations were abstracted and used to control for case-mix in models comparing the rates of reoperation and mortality after transurethral versus open prostatectomy. Several models were specified. In all models the relative risk of dying after transurethral prostatectomy remained elevated (1.36 to 1.89), as did the risk for reoperation (3.62). A prospective trial is needed to establish the relative safety and effectiveness of transurethral and open prostatectomy.

Risk of carotid endarterectomy in the elderly.

We used the Medicare claims files to describe operative mortality for 2,089 New England residents over the age of 65 who underwent carotid endarterectomy in 1984 and 1985. For patients ages 65 to 69, the risk of death within 30 days of surgery was 1.1 percent, (95% confidence interval = 0.5, 2.1), for those ages 70 to 74, 2.8 percent (1.7, 4.4), for those ages 75 to 79, 3.2 percent (1.8, 5.2), and for those over age 80, 4.7 percent (2.3, 8.5). Nearly 80 percent of patients underwent surgery at hospitals performing 40 or fewer carotid endarterectomies per year on the Medicare population. The adjusted odds ratio for 30 day mortality for patients undergoing surgery in these low-volume hospitals was 2.8 (95% CI = 1.1, 7.2) compared to higher volume hospitals. Although the Medicare claims data provided only limited data about post-operative strokes, analysis of post-operative stroke risk supported these findings.

Physical fitness as a predictor of cardiovascular mortality in asymptomatic North American men. The Lipid Research Clinics Mortality Follow-up Study.

Limited data are available on the relation between physical fitness and mortality from cardiovascular disease. We examined this question in a study of 4276 men, 30 to 69 years of age, whom we followed for an average of 8.5 years. Examinations at base line included assessment of conventional coronary risk factors and treadmill exercise testing. The heart rate during submaximal exercise (stage 2 of the exercise test) and the duration of exercise were used as measures of physical fitness. Men with incomplete data (n = 308) or who were using cardiovascular drugs (n = 213) were excluded from the analysis. Men who had clinical evidence of cardiovascular disease at base line (n = 649) were analyzed separately. Forty-five deaths from cardiovascular causes occurred among the remaining 3106 men. A lower level of physical fitness was associated with a higher risk of death from cardiovascular and coronary heart disease, after adjustment for age and cardiovascular risk factors. The relative risk of death from cardiovascular causes was 2.7 (95 percent confidence interval, 1.4 to 5.1; P = 0.003) for healthy men with an increment of 35 beats per minute in the heart rate during stage 2, and 3.0 (95 percent confidence interval, 1.6 to 5.5; P = 0.0004) for those with a decrement of 4.4 minutes in the exercise time spent on the treadmill. The corresponding values for death from coronary heart disease were 3.2 (95 percent confidence interval, 1.5 to 6.7; P = 0.003) and 2.8 (95 percent confidence interval, 1.3 to 6.1; P = 0.007), respectively. We conclude that a lower level of physical fitness is associated with a higher risk of death from coronary heart disease and cardiovascular disease in clinically healthy men, independent of conventional coronary risk factors.

Cyclic seasonal variation in plasma lipid and lipoprotein levels: the Lipid Research Clinics Coronary Primary Prevention Trial Placebo Group.

Seasonal plasma lipid and lipoprotein cycles were studied in 1446 hypercholesterolemic 35-59 year-old men followed for 7 years as the placebo group of the Lipid Research Clinics (LRC) Coronary Primary Prevention Trial (CPPT). Separate periodic time series were calculated for each study participant; mean parameter estimates were obtained by vector algebra. Highly significant (p less than 0.001) synchronous sinusoidal seasonal cycles, peaking in the first month of winter, were demonstrated for plasma levels of total (TOT-C), low-density lipoprotein (LDL-C), and high-density lipoprotein (HDL-C) cholesterol. Their mean seasonal changes (nadir to zenith) were 7.4, 6.4, and 0.8 mg/dl, respectively. An irregular but statistically significant seasonal pattern was also observed for plasma triglyceride (TG) levels, with peak levels in the autumn. The variation of these seasonal effects among subgroups and geographic locales and their correlation with seasonal weight and dietary patterns yielded few clues as to their underlying etiologic mechanisms.

Seasonal cholesterol cycles: the Lipid Research Clinics Coronary Primary Prevention Trial placebo group.

Seasonal variation of plasma cholesterol levels was studied in 1446 hypercholesterolemic 35- to 59-year-old male participants in the Lipid Research Clinics Coronary Primary Prevention Trial placebo group. Each man's serial cholesterol data, obtained at bimonthly intervals for 2.0 to 6.5 years, were analyzed as a separate periodic time series, and distributions of cycle zeniths and amplitudes were calculated. A highly significant (chi 2= 706, 2 degrees of freedom) seasonal effect, 7.4 mg/dl higher on December 30 than on June 30, was found. This effect was similar among the 12 LRC centers, including such disparate climates as those of Minneapolis and San Diego, and tended to be larger in the southern centers. Its magnitude was independent of baseline levels of plasma cholesterol and other baseline characteristics. Observed seasonal differences in weight and diet explained less than one-third of the seasonal variation in plasma cholesterol levels. Plasma low- and high-density lipoprotein cholesterol levels, analyzed similarly, also showed significant synchronous seasonal cycles. Plasma triglyceride levels showed a weaker irregular seasonal pattern, highest in midsummer and late autumn and lowest in spring. The etiologies and mechanisms for these seasonal patterns remain largely unknown.

Effects of misclassifications on statistical inferences in epidemiology.

Misclassification errors caused by imperfect sensitivity (U) and specificity (V) can affect statistical inferences in epidemiology. Such errors can lead to biases and increased standard errors in estimates of rates. Furthermore, low U and V can have a catastrophic effect on the power of a test to detect a change in rate, and, if U and V change even slightly as the rate changes, the effect on power may be dramatic.