The NordiNet International Outcome Study and NovoNet ANSWER Program : rationale, design, and methodology of two international pharmacoepidemiological registry-based studies monitoring long-term clinical and safety outcomes of growth hormone therapy (Norditropin )

Charlotte H ybye,1 Lars S vendahl,2 Henrik Thybo Christesen,3 Peter Lee,4 Birgitte T nnes Pedersen,5 Michael Schlumpf,6 John Germak,7 Judith Ross8 1Department of Molecular Medicine and Surgery, Karolinska Institute and Department of Endocrinology, Metabolism and Diabetes, 2Department of Women’s and Children’s Health, Karolinska Institute and Division of Pediatrics, Karolinska University Hospital, Stockholm, Sweden; 3Hans Christian Andersen Children’s Hospital, Odense University Hospital, Odense, Denmark; 4Department of Pediatrics, Penn State College of Medicine, Hershey, PA, USA; 5Global Development, Novo Nordisk A/S, S borg, Denmark; 6Global Medical Affairs Biopharm, Novo Nordisk Health Care AG, Zurich, Switzerland; 7Clinical Development and Medical Affairs, Novo Nordisk Inc, Princeton, NJ, USA; 8Department of Pediatrics, Thomas Jefferson University, Philadelphia, PA, USA Objective: Randomized controlled trials have shown that growth hormone (GH) therapy has effects on growth, metabolism, and body composition. GH therapy is prescribed for children with growth failure and adults with GH deficiency. Carefully conducted observational study of GH treatment affords the opportunity to assess long-term treatment outcomes and the clinical factors and variables affecting those outcomes, in patients receiving GH therapy in routine clinical practice. Design: The NordiNet International Outcome Study (IOS) and the American Norditropin Studies: Web Enabled Research (ANSWER Program ) are two complementary, non-interventional, observational studies that adhere to current guidelines for pharmacoepidemiological data. Patients: The studies include pediatric and adult patients receiving Norditropin , as prescribed by their physicians. Measurements: The studies gather long-term data on the safety and effectiveness of real-life treatment with the recombinant human GH, Norditropin . We describe the origins, aims, objectives, and design methodology of the studies, as well as their governance and validity, strengths, and limitations. Conclusion: The NordiNet IOS and ANSWER Program studies will provide valid insights into the effectiveness and safety of GH treatment across a diverse and large patient population treated in accordance with real-world clinical practice and following the Good Pharmacoepidemiological Practice and STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) guidelines. Keywords: growth hormone replacement therapy, treatment outcome, pharmacoepidemiology, survey