RESUMO
Randomized clinical trials (RCTs) are among the most rigorous ways to determine the causal relationship between an intervention and important clinical outcome. Their use in veterinary medicine has become increasingly common, and as is often the case, with progress comes new challenges. Randomized clinical trials yield important answers, but results from these studies can be unhelpful or even misleading unless the study design and reporting are carried out with care. Herein, we offer some perspective on several emerging challenges associated with RCTs, including use of composite endpoints, the reporting of different forms of risk, analysis in the presence of missing data, and issues of reporting and safety assessment. These topics are explored in the context of previously reported veterinary internal medicine studies as well as through illustrative examples with hypothetical data sets. Moreover, many insights germane to RCTs in veterinary internal medicine can be drawn from the wealth of experience with RCTs in the human medical field. A better understanding of the issues presented here can help improve the design, interpretation, and reporting of veterinary RCTs.
Assuntos
Ensaios Clínicos Controlados Aleatórios como Assunto/veterinária , Animais , Confiabilidade dos Dados , Interpretação Estatística de Dados , Determinação de Ponto Final/veterinária , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Medição de Risco , Resultado do Tratamento , Medicina Veterinária/métodosRESUMO
OBJECTIVE: To provide an overview of the data, function, and performance of the Vaccine Adverse Event Reporting System. DESIGN: Descriptive and correlational analyses. SETTING: United States, 1991 through 1994. SUBJECTS: Reports to the Vaccine Adverse Event Reporting System, a passive national surveillance system, that represents temporal (but not necessarily causal) relationships between vaccinations and adverse events. MAIN OUTCOME MEASURES: Demographic variables, birth weight, vaccine type, severity of adverse event after immunization. RESULTS: A total of 38,787 adverse events was reported during the study period without a clearly increasing or decreasing trend in the annual number of total reports or deaths. Of the deaths with known age, 72.4% were reported in the first year of life, and 63.7% of these were male. The peak age for death reports was 1 to 3 months, with a gradual decline through age 9 months, after which death was relatively rare. Adverse events with onset of symptoms the day of vaccination accounted for 45.5% of total reports; 20.4% had onset of symptoms the following day. Onset within 2 weeks after vaccination was noted for 92.5% of all reports. Simultaneous administration of multiple vaccines was noted in 75.7% of reports for immunizations at ages younger than 20 years. In contrast, among those 20 years or older, only 6.0% of reports named multiple vaccines. Wide geographic variations were noted in adverse event reporting rates for children younger than 2 years, and the states with the lowest reporting rates of less serious events included the most populous states. CONCLUSIONS: The peak age of deaths at ages 1 to 3 months could be expected on the basis of prior studies showing that sudden infant death syndrome deaths peak at that age, that most deaths in the Vaccine Adverse Event Reporting System are attributed to sudden infant death syndrome, and that sudden infant death syndrome has not been associated with vaccination. The large number of reports and national coverage of the Vaccine Adverse Events Reporting System make it useful for monitoring the safety of vaccine lots and for accumulating case series to detect or better understand adverse events that may occur too rarely to be assessed in clinical trials or in the larger studies that are sometimes carried out by manufacturers after vaccine licensure (phase IV studies).
Assuntos
Morte Súbita do Lactente/epidemiologia , Morte Súbita do Lactente/etiologia , Vacinação/efeitos adversos , Adolescente , Adulto , Idoso , Peso ao Nascer , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , MortalidadeRESUMO
About a third of patients with ovarian cancer present with localized disease; despite surgical resection, up to half the tumors recur. Since it has not been established whether adjuvant treatment can benefit such patients, we conducted two prospective, randomized national cooperative trials of adjuvant therapy in patients with localized ovarian carcinoma (International Federation of Gynecology and Obstetrics Stages Ia to IIc). All patients underwent surgical resection plus comprehensive staging and, 18 months later, surgical re-exploration. In the first trial, 81 patients with well-differentiated or moderately well differentiated cancers confined to the ovaries (Stages Iai and Ibi) were assigned to receive either no chemotherapy or melphalan (0.2 mg per kilogram of body weight per day for five days, repeated every four to six weeks for up to 12 cycles). After a median follow-up of more than six years, there were no significant differences between the patients given no chemotherapy and those treated with melphalan with respect to either five-year disease-free survival (91 vs. 98 percent; P = 0.41) or overall survival (94 vs. 98 percent; P = 0.43). In the second trial, 141 patients with poorly differentiated Stage I tumors or with cancer outside the ovaries but limited to the pelvis (Stage II) were randomly assigned to treatment with either melphalan (in the same regimen as above) or a single intraperitoneal dose of 32P (15 mCi) at the time of surgery. In this trial (median follow-up, greater than 6 years) the outcomes for the two treatment groups were similar with respect to five-year disease-free survival (80 percent in both groups) and overall survival (81 percent with melphalan vs. 78 percent with 32P; P = 0.48). We conclude that in patients with localized ovarian cancer, comprehensive staging at the time of surgical resection can serve to identify those patients (as defined by the first trial) who can be followed without adjuvant chemotherapy. The remaining patients with localized ovarian cancer should receive adjuvant therapy, and with adjuvant melphalan or intraperitoneal 32P should have a five-year disease-free survival of about 80 percent.