David Harris

Purpose: During preclinical testing, teriparatide caused a dose‐dependent increase in the incidence of osteosarcoma in rats. This study compared the incidence rate of osteosarcoma among patients aged ≥65 years treated with teriparatide vs a matched‐comparator cohort.Methods: This population‐based comparative‐cohort study matched exposure details for each teriparatide user, identified via Medicare Part D prescription claims, and up to four comparators based on age, sex, zip code, date of claim for filled prescription, and number of unique therapeutic classes dispensed. Outcomes were identified via linkage with participating cancer registries. All US state cancer registries were invited to participate.Results: Overall, 153 316 patients in the teriparatide cohort and 613 247 in the comparator cohort were linked to 811 osteosarcoma cases from 26 participating state cancer registries (68% of US patients aged ≥65 years diagnosed 2007‐2014). Analysis on a subset of cohorts revealed they were balanced for known osteosarcoma risk factors and Charlson comorbidity index. Mean duration of teriparatide treatment was 10 months. No osteosarcoma cases were observed in the teriparatide cohort; the incidence rate in the comparator cohort was consistent with the background incidence rate among adults aged ≥65 years. The incidence rate ratio was 0.0 (95% confidence interval, 0.0‐3.2).Conclusions: For US patients aged ≥65 years, incidence of osteosarcoma among those treated with teriparatide ranges from 0 to 3.2 times the incidence of osteosarcoma in those treated with other medications. Given low incidence of osteosarcoma, this range of effect is inconsistent with a large absolute increase in osteosarcoma risk.

Summary 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.

We quantified the contribution to pharmacoepidemiologic research of studies conducted in automated health care databases over the last decade. We reviewed abstracts accepted at the International Conference of Pharmacoepidemiology in 2000 and 2011 to identify studies on drug safety, drug utilization, validation of database data, and disease epidemiology conducted in databases. We abstracted data on study objectives, database name and country, and number of databases used in each study. The total number of ICPE abstracts doubled from 389 in 2000 to 806 in 2011. Abstracts on database studies contributed 36 percent (139 of 389) of all abstracts in 2000 and 45 percent (360 of 806) in 2011. The most common study objective in both years was to evaluate drug safety. Abstracts on validation of database data increased from 2 to 39. Multiple-database abstracts increased from 9 to 43. The number of countries contributing to database abstracts increased from 14 to 22; the increase in countries was primarily in Europe and the Asian Pacific region. This study indicates that the use of health care databases in pharmacoepidemiologic research is growing in many countries. The different types of database studies and the number of studies conducted using multiple databases is also increasing, suggesting that larger study populations and greater collaboration among investigators are becoming more common.

When a patient develops acute venous thromboembolism (VTE), physicians commonly try to determine whether there is an underlying condition or risk factor associated with the thrombotic event. Patients with a provoking risk factor, such as recent trauma, major surgery, or immobility, have a better long-term prognosis with a lower incidence of recurrent VTE than patients who present with unprovoked VTE.¹ In the absence of an obvious provoking risk factor, the presence of an underlying malignancy is often considered.^2,3 This is because some types of cancer appear to be able to initiate or trigger a thrombotic diathesis through a number of mechanisms, which have been recently reviewed.^4,5 Several cohort studies have suggested that the incidence of cancer among patients who present with unprovoked VTE is more than 3 times higher than among patients with a provoked VTE,^6-12 and there is evidence that more than 40% of these cancers are metastatic at the time of diagnosis.¹³