Abstract
Background
This study compared the effectiveness of recombinant human follicle-stimulating hormone alfa (r-hFSH-alfa; GONAL-f
®
) with urinary highly purified human menopausal gonadotropin ...(hMG HP; Menogon HP
®
), during assisted reproductive technology (ART) treatments in Germany.
Methods
Data were collected from 71 German fertility centres between 01 January 2007 and 31 December 2012
,
for women undergoing a first stimulation cycle of ART treatment with r-hFSH-alfa or hMG HP. Primary outcomes were live birth, ongoing pregnancy and clinical pregnancy, based on cumulative data (fresh and frozen-thawed embryo transfers), analysed per patient (pP), per complete cycle (pCC) and per first complete cycle (pFC). Secondary outcomes were pregnancy loss (analysed per clinical pregnancy), cancelled cycles (analysed pCC), total drug usage per oocyte retrieved and time-to-live birth (TTLB; per calendar week and per cycle).
Results
Twenty-eight thousand six hundred forty-one women initiated a first treatment cycle (r-hFSH-alfa: 17,725 61.9%; hMG HP: 10,916 38.1%). After adjustment for confounding variables, treatment with r-hFSH-alfa versus hMG HP was associated with a significantly higher probability of live birth (hazard ratio HR-pP 95% confidence interval (CI): 1.10 1.04, 1.16; HR-pCC 95% CI: 1.13 1.08, 1.19; relative risk RR-pFC 95% CI: 1.09 1.05, 1.15, ongoing pregnancy (HR-pP 95% CI: 1.10 1.04, 1.16; HR-pCC 95% CI: 1.13 1.08, 1.19; RR-pFC 95% CI: 1.10 1.05, 1.15) and clinical pregnancy (HR-pP 95% CI: 1.10 1.05, 1.14; HR-pCC 95% CI: 1.14 1.10, 1.19; RR-pFC 95% CI: 1.10 1.06, 1.14). Women treated with r-hFSH-alfa versus hMG HP had no statistically significant difference in pregnancy loss (HR 95% CI: 1.07 0.98, 1.17, were less likely to have a cycle cancellation (HR 95% CI: 0.91 0.84, 0.99) and had no statistically significant difference in TTLB when measured in weeks (HR 95% CI: 1.02 0.97, 1.07;
p
= 0.548); however, r-hFSH-alfa was associated with a significantly shorter TTLB when measured in cycles versus hMG HP (HR 95% CI: 1.07 1.02, 1.13;
p
= 0.003). There was an average of 47% less drug used per oocyte retrieved with r-hFSH-alfa versus hMG HP.
Conclusions
This large (> 28,000 women), real-world study demonstrated significantly higher rates of cumulative live birth, cumulative ongoing pregnancy and cumulative clinical pregnancy with r-hFSH-alfa versus hMG HP.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This reflection paper presents a consolidated view of EFPIA on the need for principles for good practice in the generation and use of non-interventional studies (NIS), including overarching ...principles such as the registration of hypothesis evaluating treatment effect (HETE) studies. We first define NIS and the important adjacencies to clinical trials and relationship with real-world evidence (RWE). We then outline the principles for good practice with respect to appropriate research design, study protocol, fit-for-purpose variables and data quality, analytical methods, bias reduction, transparency in conduct and use, privacy management and ethics review. We conclude with recommendations for action for the research community to promote trust and credibility in the use of NIS.
Real‐world data (RWD) reflecting patient treatment in routine clinical practice can be used to develop external control groups for single‐arm trials. External controls can provide valuable benchmark ...results on potential comparator drug effectiveness, particularly in rare indications when randomized controlled trials are either infeasible or unethical. This paper describes lessons learned from a descriptive real‐world external control cohort study conducted to provide benchmark data for a single‐arm clinical trial in a rare oncology biomarker driven disease. Conducting external control cohort studies to evaluate treatment effectiveness in rare indications likely will present data and analysis challenges as seen in the example study. However, there are mitigating measures that can be applied in the study design, identification of RWD sources, and data analysis. The lessons learned and reported here with a proposal of an external control study framework can provide guidance for future research in this area, and may be applicable as well in other rare indications. Taking these learnings into consideration, the use of real‐world external controls to contextualize treatment effectiveness in rare indications is a valuable approach and warrants further application in the future.
Patient experience data (PED), provided by patients/their carers without interpretation by clinicians, directly capture what matters more to patients on their medical condition, treatment and impact ...of healthcare. PED can be collected through different methodologies and these need to be robust and validated for its intended use. Medicine regulators are increasingly encouraging stakeholders to generate, collect and submit PED to support both scientific advice in development programs and regulatory decisions on the approval and use of these medicines. This article reviews the existing definitions and types of PED and demonstrate the potential for use in different settings of medicines’ life cycle, focusing on Patient-Reported Outcomes (PRO) and Patient Preferences (PP). Furthermore, it addresses some challenges and opportunities, alluding to important regulatory guidance that has been published, methodological aspects and digitalization, highlighting the lack of guidance as a key hurdle to achieve more systematic inclusion of PED in regulatory submissions. In addition, the article discusses opportunities at European and global level that could be implemented to leverage PED use. New digital tools that allow patients to collect PED in real time could also contribute to these advances, but it is equally important not to overlook the challenges they entail. The numerous and relevant initiatives being developed by various stakeholders in this field, including regulators, show their confidence in PED’s value and create an ideal moment to address challenges and consolidate PED use across medicines’ life cycle.
Background Detailed epidemiologic descriptions of large populations of advanced stage ovarian cancer patients have been lacking to date. This study aimed to describe the patient characteristics, ...treatment patterns, survival, and incidence rates of health outcomes of interest (HOI) in a large cohort of advanced stage ovarian cancer patients in the United States (US). Methods This cohort study identified incident advanced stage (III/IV) ovarian cancer patients in the US diagnosed from 2010 to 2018 in the HealthCore Integrated Research Database (HIRD) using a validated predictive model algorithm. Descriptive characteristics were presented overall and by treatment line. The incidence rates and 95% confidence intervals for pre-specified HOIs were evaluated after advanced stage diagnosis. Overall survival, time to treatment discontinuation or death (TTD), and time to next treatment or death (TTNT) were defined using treatment information in claims and linkage with the National Death Index. Results We identified 12,659 patients with incident advanced stage ovarian cancer during the study period. Most patients undergoing treatment received platinum agents (75%) and/or taxanes (70%). The most common HOIs (> 24 per 100 person-years) included abdominal pain, nausea and vomiting, anemia, and serious infections. The median overall survival from diagnosis was 4.5 years, while approximately half of the treated cohort had a first-line time to treatment discontinuation or death (TTD) within the first 4 months, and a time to next treatment or death (TTNT) from first to second-line of about 6 months. Conclusions This study describes commercially insured US patients with advanced stage ovarian cancer from 2010 to 2018, and observed diverse treatment patterns, incidence of numerous HOIs, and limited survival in this population. Keywords: Epidemiology, Ovarian Cancer, Advanced stage, Treatment patterns, Health outcome of interest, Survival
High‐dose corticosteroids have been associated with increased risk of serious infection in patients with metastatic melanoma treated with immune checkpoint inhibitors targeting cytotoxic T‐lymphocyte ...antigen 4. This potential association needs to be examined further among patients with other cancer types and for other immune checkpoint inhibitors. We examined whether receipt of high‐dose corticosteroids was associated with increased rates of hospitalization for infection among 981 Danish renal, urothelial, and lung cancer patients followed from first administration of programmed death receptor 1 (PD‐1)/programmed death ligand 1 (PD‐L1) immune checkpoint inhibitors. Our cohort analysis was based on the information from national medical registries. During follow‐up, 522 patients (53.2%) initiated treatment with high‐dose corticosteroids and 317 patients (32.3%) experienced at least one hospitalization for infection. In analyses adjusted for age, sex, and previous use of chemotherapy/targeted therapy, initiation of high‐dose systemic corticosteroids was associated with increased rate of hospitalization for infections (hazard ratio (HR) = 2.96, 95% confidence interval (CI) = 2.41–3.65) even in patients not receiving any chemotherapy/targeted therapy (HR = 3.66, 95% CI = 2.25–5.96). Our findings showed that high‐dose corticosteroid initiation is associated with hospitalization for infection in patients treated with PD‐1/PD‐L1 immune checkpoint inhibitors. Clinicians and patients should be aware of this risk of infection when initiating treatment with high‐dose corticosteroids.
High‐dose corticosteroids have been associated with increased risk of serious infection in metastatic melanoma patients treated with immune checkpoint inhibitors (ICIs) targeting cytotoxic T‐lymphocyte antigen 4. The present study adds that use of high‐dose corticosteroids is also associated with increased rate of hospitalization for infection among lung, kidney, and urothelial cancer patients treated with ICIs targeting programmed death receptor 1 or programmed death ligand 1 even in patients who did not receive chemotherapy/targeted therapy.
We describe and compare the availability and accessibility of administrative healthcare databases (AHDB) in several Asia-Pacific countries: Australia, Japan, South Korea, Taiwan, Singapore, China, ...Thailand, and Malaysia.
The study included hospital records, reimbursement databases, prescription databases, and data linkages. Databases were first identified through PubMed, Google Scholar, and the ISPOR database register. Database custodians were contacted. Six criteria were used to assess the databases and provided the basis for a tool to categorise databases into seven levels ranging from least accessible (Level 1) to most accessible (Level 7). We also categorised overall data accessibility for each country as high, medium, or low based on accessibility of databases as well as the number of academic articles published using the databases.
Fifty-four administrative databases were identified. Only a limited number of databases allowed access to raw data and were at Level 7 Medical Data Vision EBM Provider, Japan Medical Data Centre (JMDC) Claims database and Nihon-Chouzai Pharmacy Claims database in Japan, and Medicare, Pharmaceutical Benefits Scheme (PBS), Centre for Health Record Linkage (CHeReL), HealthLinQ, Victorian Data Linkages (VDL), SA-NT DataLink in Australia. At Levels 3-6 were several databases from Japan Hamamatsu Medical University Database, Medi-Trend, Nihon University School of Medicine Clinical Data Warehouse (NUSM), Australia Western Australia Data Linkage (WADL), Taiwan National Health Insurance Research Database (NHIRD), South Korea Health Insurance Review and Assessment Service (HIRA), and Malaysia United Nations University (UNU)-Casemix. Countries were categorised as having a high level of data accessibility (Australia, Taiwan, and Japan), medium level of accessibility (South Korea), or a low level of accessibility (Thailand, China, Malaysia, and Singapore). In some countries, data may be available but accessibility was restricted based on requirements by data custodians.
Compared with previous research, this study describes the landscape of databases in the selected countries with more granularity using an assessment tool developed for this purpose. A high number of databases were identified but most had restricted access, preventing their potential use to support research. We hope that this study helps to improve the understanding of the AHDB landscape, increase data sharing and database research in Asia-Pacific countries.
Background and objective: A Depressive Health State Index (DHSI) based on 29 parameters routinely collected in an automated healthcare database (AHDB) was developed to evaluate the health state of ...depressive patients, and its evolution. The study objective was to describe and validate this DHSI.
Methods: A historical cohort of patients with at least one episode of depression was identified in the Clinical Practice Research Datalink (CPRD). The DHSI was calculated for each episode of depression. Validation was performed by comparing the DHSI between subgroups and using validated definitions of remission (proxy and PHQ-9). Robustness was studied by assessing the impact of modifying parameters of the DHSI.
Results: 309,279 episodes of depression were identified in the CPRD between 1 January 2006 and 31 December 2012. Remission was observed in 8% of the patients showing the lower DHSI scores and in 88% of the patients showing the higher DHSI scores. The DHSI was robust to a modification of the most frequent variables and to the removal of rare parameters.
Conclusion: The DHSI is specific to depression severity (with remission rates in accordance with the expected variations of the DHSI) and robust. It represents a promising tool for the analysis of AHDBs.
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