Design and methods for a Scandinavian pharmacovigilance study of osteonecrosis of the jaw and serious infections among cancer patients treated with antiresorptive agents for the prevention of skeletal-related events

John Acquavella,1 Vera Ehrenstein,1 Morten Schiødt,2 Uffe Heide-Jørgensen,1 Anders Kjellman,3,4 Svein Hansen,5 Cecilia Larsson Wexell,6,7 Bente Brokstad Herlofson,8 Sven Erik Noerholt,9 Haijun Ma,10 Katarina Öhrling,11 Rohini K Hernandez,12 Henrik Toft Sørensen1 1Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 2Department of Oral and Maxillofacial Surgery, Rigshospitalet, Copenhagen, Denmark; 3Department of Urology, Karolinska University Hospital, 4Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden; 5Cancer Registry of Norway, Oslo University Hospital, Oslo, Norway; 6Department of Oral and Maxillofacial Surgery, Södra Älvsborg Hospital, Borås, Sweden; 7Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 8Department of Oral Surgery and Oral Medicine, Faculty of Dentistry, University of Oslo, Oslo, Norway; 9Department of Oral and Maxillofacial Surgery, Aarhus University Hospital, Aarhus, Denmark; 10Global Biostatistical Science, Amgen Inc., Thousand Oaks, CA, USA; 11Clinical Development, Amgen Inc., Thousand Oaks, CA, USA; 12Center for Observational Research, Amgen Inc., Thousand Oaks, CA, USA Objective: Osteonecrosis of the jaw (ONJ) is a recognized complication of potent antiresorptive therapies, especially at the doses indicated to prevent skeletal complications for cancer patients with bone metastases. This paper describes the rationale and methods for a prospective, post-authorization safety study of cancer patients treated with antiresorptive therapies. Methods: As part of a comprehensive pharmacovigilance plan, developed with regulators’ input, the study will estimate incidence of ONJ and of serious infections among adult cancer patients with bone metastases treated with denosumab (120 mg subcutaneously) or zoledronic acid (