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®)

Abstract

ObjectiveRandomized 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.DesignThe 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.PatientsThe studies include pediatric and adult patients receiving Norditropin®, as prescribed by their physicians.MeasurementsThe studies gather long-term data on the safety and effectiveness of reallife 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.ConclusionThe 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.

Is safety of childhood growth hormone therapy related to dose? Data from a large observational study

“…Differences in population genetics, environmental or other unidentified confounding factors, as well as variable local clinical practices may also have an impact on study results. Nevertheless, it is worth noting that validation of data at data entry (24), systematic checks for outliers, and elimination of obvious data entry errors were undertaken methodically. The finding that approximately two-thirds of AEs were reported outside of the regular scheduled clinic visits also suggests that the degree of under-reporting of AEs was limited.…”

“…We report long-term safety data for 13 (24). Patients without confirmation of diagnosis at baseline were excluded from the analysis.…”

“…NordiNet ® IOS is conducted in accordance with the Declaration of Helsinki guidelines and all applicable regulatory requirements in the participating countries: guardians provide written informed consent for data collection. All data within NordiNet ® IOS are anonymized, and local ethics committee or institutional review board approval is a prerequisite for each center's inclusion in NordiNet ® IOS (24).…”

“…Hence, the total number of reported events will be the sum of SAEs and ADRs minus the number of SADRs. Safety information was captured in the study case report form via an electronic, web-based, platform ( NordiNet ® ) (24). All ADRs, SAEs, and SADRs were coded with the Medical Dictionary for Regulatory Activities (MedDRA) terms (Version 14.0) using the System Organ Class (SOC) terminology.…”

“…Novo Nordisk A/S, Denmark) as prescribed by the treating physicians in the everyday clinical practice setting (24). In this study, we evaluated the incidence rates (IRs) of adverse events (AEs) reported in NordiNet ® IOS during GH treatment in pediatric patients with short stature classified by risk for mortality as well as the impact of GH dose on the IRs for AEs during GH treatment.…”