An Extraterritorial FDA: Could the Food and Drug Administration Apply Its Informed Consent Requirement Abroad Consistent with International Law?

This paper addresses the regulatory challenges wrought by the increasing amount of human subject drug testing conducted in developing countries in support of new drug applications to the Food and Drug Administration. Specifically, it examines the difficulty of enforcing the “informed consent” requirement for ethical scientific research performed in foreign territory. In poorer regions, a lack of government oversight, lower regulatory standards, and barriers to communication have too frequently resulted in allegations of human experimentation performed without its participants’ informed consent. In order to solve this problem, some commentators have suggested that the FDA could apply its human subject protections to foreign clinical research, and enforce them through injunctions or criminal prosecutions. However, the international legal limits on states’ prescriptive jurisdiction may prohibit this exercise of extraterritoriality. After analyzing the proposed extraterritorial regulation of foreign drug testing under the traditional bases and limitations of prescriptive jurisdiction, this paper concludes that such regulation would likely violate international law. However, because nonconsensual clinical research has previously been regarded as a crime against humanity, the FDA might be able to bring criminal prosecutions under the principal of “universal jurisdiction” against investigators or sponsors who conducted studies without their subjects’ informed consent. This analysis offers both positive and normative conclusions regarding the international legal system and the human rights regime

Effect of acetylsalicylic acid on thalassemia with pulmonary arterial hypertension

Nonlawan Chueamuangphan,1,2 Wattana Wongtheptian,2 Jayanton Patumanond,3 Apichard Sukonthasarn,4 Suporn Chuncharunee,5 Chamaiporn Tawichasri,6 Weerasak Nawarawong4 1Clinical Epidemiology Program, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; 2Department of Medicine, Chiang Rai Hospital, Chiang Rai, Thailand; 3Clinical Epidemiology Program, Faculty of Medicine, Thammasat University, Bangkok, Thailand; 4Department of Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; 5Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 6Clinical Epidemiology Society at Chiang Mai, Chiang Mai, Thailand Objective: To compare pulmonary artery systolic pressure (PASP) between thalassemic patients with pulmonary arterial hypertension (PAH) for whom acetylsalicylic acid (ASA) was and was not prescribed after 1 year. Methods: A retrospective cohort study was conducted at the hematological outpatient clinic at Chiang Rai Hospital, Chiang Rai, Thailand. All new cases of thalassemia with PAH from January 2007 to January 2012 were studied at the first month and at 12 months. The patients were classified into two groups. In one group, ASA 81 mg daily was prescribed for 1 year, whereas in another group no ASA was prescribed, due to its contraindications, which included bleeding, gastrointestinal side effects, and thrombocytopenia. PASP, estimated by a Doppler echocardiography, was measured by the same cardiologist. Propensity score adjustment was used to control confounding variables by indication and contraindication. Multivariable regression analysis was used to evaluate the effects of ASA. Results: Of the 63 thalassemia patients with PAH, there were 47 (74.6%) in the ASA group and 16 (25.4%) in the no ASA group. ASA, as compared with no ASA, did not significantly reduce PASP (adjusted difference -0.95; 95% confidence interval -16.99 to 15.10; P=0.906). Conclusion: Low-dose ASA may not have a beneficial effect on PASP after 1 year of treatment of PAH in thalassemia. Keywords: thalassemia, pulmonary arterial hypertension, acetylsalicylic aci

Defining serum ferritin thresholds to predict clinically relevant liver iron concentrations for guiding deferasirox therapy when MRI is unavailable in patients with non-transfusion-dependent thalassaemia

Summary: Liver iron concentration (LIC) assessment by magnetic resonance imaging (MRI) remains the gold standard to diagnose iron overload and guide iron chelation therapy in patients with non-transfusion-dependent thalassaemia (NTDT). However, limited access to MRI technology and expertise worldwide makes it practical to also use serum ferritin assessments. The THALASSA (assessment of Exjade® in non-transfusion-dependent THALASSemiA patients) study assessed the efficacy and safety of deferasirox in iron-overloaded NTDT patients and provided a large data set to allow exploration of the relationship between LIC and serum ferritin. Using data from screened patients and those treated with deferasirox for up to 2 years, we identified clinically relevant serum ferritin thresholds (for when MRI is unavailable) for the initiation of chelation therapy (>800 μg/l), as well as thresholds to guide chelator dose interruption (<300 μg/l) and dose escalation (>2000 μg/l). (clinicaltrials.gov identifier: NCT00873041). © 2014 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd