Long-term cancer surveillance: results from the Forteo Patient Registry Surveillance Study.

The Forteo Patient Registry estimated the incidence of osteosarcoma in US patients treated with teriparatide and enrolled in the study between 2009 and 2019. No incident cases of osteosarcoma were identified among patients registered, and the crude incidence rate was 0 (95% confidence interval [CI], 0-10.2) cases per million person-years. PURPOSE: The prospective, voluntary Forteo Patient Registry was established to estimate the incidence of osteosarcoma in patients who have received treatment with teriparatide (Forteo). METHODS: Information on US adults prescribed teriparatide and enrolled in the Forteo Patient Registry 2009-2019 was linked with data from participating state cancer registries annually (2010-2019) to identify incident osteosarcoma cases using a standardized linkage algorithm. Teriparatide exposure was ascertained from self-reported data that included teriparatide initiation and demographics necessary to complete linkage. Osteosarcoma cases diagnosed on or after January 1, 2009, were identified by participating state cancer registries. The crude incidence rate (IR) and standardized incidence ratio (SIR) of observed cases to the expected number of cases adjusted to the background rate (3 per million person-years) and corresponding 95% CIs for the occurrence of osteosarcoma were calculated whereby the cumulative amount of person-time observed was adjusted for mortality. RESULTS: Data for 75,247 enrolled patients (representing 361,763 cumulative person-years) were linked to each of 42 participating state cancer registries (covering 93% of the US population), which included information on 6180 cases of osteosarcoma. No matches with incident cases of osteosarcoma following registry enrollment were found. The crude IR was 0 (95% CI, 0-10.2) cases per million person-years and the SIR was 0 (95% CI, 0-3.0). CONCLUSIONS: The ability to draw conclusions about the incidence of osteosarcoma among patients participating in the registry was limited due to the smaller than expected amount of patient follow-up time and the fact that no cases were identified.

The Forteo Patient Registry linkage to multiple state cancer registries: study design and results from the first 8 years.

The Forteo Patient Registry (FPR) aims to estimate the incidence of osteosarcoma in US patients treated with teriparatide. Enrollment began in 2009 and will continue through 2019, with linkage planned through 2024. To date, no incident cases of osteosarcoma have been identified among patients registered in the FPR. INTRODUCTION: The Forteo Patient Registry (FPR) was established in 2009 to estimate the incidence of osteosarcoma in US patients treated with teriparatide. The objective of this paper is to describe study methods, challenges encountered, and progress to date. METHODS: The FPR is a prospective US registry designed to link data from participants annually with state cancer registries. Patient enrollment is planned for 10 years (2009-2019) and annual linkage with US state cancer registries for 15 years (2010-2024). All US state cancer registries and DC were invited to participate. Patients are recruited using pre-enrollment materials included in teriparatide device packaging, kits, and brochures distributed by health-care providers; a toll-free number; and a study website. A linkage algorithm is used to match data from enrolled participants with cancer registry data. RESULTS: For the eighth annual linkage in 2017, information necessary for linkage with 63,270 patients in the FPR was submitted to each of the 42 participating registries. These patients contributed approximately 242,782 person-years of follow-up. A total of 5268 adult osteosarcoma cases diagnosed since January 1, 2009, were available for linkage from participating state cancer registries. To date, no incident cases of osteosarcoma have been identified among patients registered in the FPR. CONCLUSIONS: Based on the estimated 242,782 person-years of observation as of the eighth annual linkage and projecting current enrollment rate to study end in 2024, it is anticipated that the completed study will be able to detect a fourfold increase in the risk of osteosarcoma if one exists.

Application of the BRAT framework to case studies: observations and insights.

The BRAT Framework is a set of flexible processes and tools that provides a structured approach to pharmaceutical benefit-risk decision making in drug development and post approval settings. A work in progress, it consists of six steps that produce representations of key tradeoffs, with appropriate documentation of the rationale for decisions and the assumptions made in their development. This article describes insights, gained from case studies, into the Framework's performance in a variety of constructed benefit-risk scenarios, focusing on a hypothetical example of a triptan for migraine. The scenarios described illustrate the challenges inherent in arriving at many of the regulatory decisions, including obtaining data for matching populations for all outcomes, finding data of consistent quality, addressing correlated outcomes (e.g., elevated liver function tests and hepatitis rates), dealing with rare but serious adverse events (AEs), and understanding and making decisions based on information for many outcomes simultaneously. The Framework provides a structure for organizing, interpreting, and communicating relevant information, including heterogeneity in results and the quality and level of uncertainty of data, in order to facilitate benefit-risk decisions.

Prevalence of lower urinary tract symptoms and prostate enlargement in the primary care setting.

PURPOSE: Men with lower urinary tract symptoms (LUTS) from benign prostatic hyperplasia often do not discuss their symptoms with their primary care physicians (PCPs). The primary objectives of this study were to estimate the prevalence of LUTS, prostate enlargement, and prostate-specific antigen (PSA) > or = 1.5 ng/ml in men visiting their PCP and to assess patients' intent to discuss LUTS with their PCP. METHODS: Men over age 50 presenting for a routine office visit at one of six PCP offices during the 8-week data collection period were invited to participate in this cross-sectional study. Men with prostate cancer, bladder cancer, indwelling urethral catheter or previous pelvic irradiation were excluded. Four hundred and forty-four men were enrolled and completed a self-administered questionnaire [including the International Prostate Symptom Score (IPSS)], provided a blood sample for PSA, and underwent a digital rectal examination (DRE), with the prostate classified as enlarged or non-enlarged by their PCP. RESULTS: Forty-two per cent of men had IPSS > 7; 48% had an enlarged prostate based on DRE and 43% had PSA > or = 1.5 ng/ml. Twenty-nine per cent (n = 129) of men had IPSS > 7 and enlarged prostate or PSA > or = 1.5 ng/ml. Of these men, 33% (n = 42) intended to discuss their symptoms with their PCP. CONCLUSIONS: Although a significant percentage of men in this older population had enlarged prostate and LUTS, only one-third of them intended to discuss their symptoms with their physician. PCPs may need to increase efforts to detect LUTS and enlarged prostate in older men.

Similar effectiveness of paroxetine, fluoxetine, and sertraline in primary care: a randomized trial.

CONTEXT: Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed class of antidepressant, yet it is not known whether one SSRI is more effective than another. OBJECTIVE: To compare the effectiveness of 3 SSRIs (paroxetine, fluoxetine, and sertraline) in depressed primary care patients. DESIGN: Open-label, randomized, intention-to-treat trial, with patient enrollment occurring in April-November 1999. SETTING: Thirty-seven clinics in 2 US primary care research networks. PATIENTS: A total of 573 depressed adult patients for whom their primary care physician thought that antidepressant therapy was warranted and who completed a baseline interview. INTERVENTIONS: Patients were randomly assigned to receive paroxetine (n = 189), fluoxetine (n = 193), or sertraline (n = 191) for 9 months. Primary care physicians were allowed to switch patients to a different SSRI or non-SSRI antidepressant if they did not adequately respond to or tolerate the initial SSRI. MAIN OUTCOME MEASURES: The primary outcome measure was change in the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) Mental Component Summary score (range, 0-100), compared across treatment groups at 1, 3, 6, and 9 months. Secondary outcomes included other depression and psychological measures, multiple measures of social and work functioning, and other domains of health-related quality of life, such as physical functioning, concentration and memory, vitality, bodily pain, sleep, and sexual functioning. RESULTS: Follow-up interviews were successfully completed in 94% of patients at 1 month, 87% at 3 months, 84% at 6 months, and 79% at 9 months. Responses to the 3 SSRIs were comparable on all measures and at all time points. The mean change in the SF-36 Mental Component Summary score at 9 months was + 15.8 in the paroxetine group, + 15.1 in the fluoxetine group, and + 17.4 in the sertraline group. The drugs were also associated with similar incidences of adverse effects and discontinuation rates. CONCLUSIONS: The SSRI antidepressants paroxetine, fluoxetine, and sertraline were similar in effectiveness for depressive symptoms as well as multiple domains of health-related quality of life over the entire 9 months of this trial.