Long-Term Efficacy and Safety of Hizentra® in Patients with Primary Immunodeficiency in Japan, Europe, and the United States: a Review of 7 Phase 3 Trials.
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SUBMITTER: Jolles S
PROVIDER: S-EPMC6292970 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ContextUnderstanding real-world prescribing of GH may help improve treatment of eligible patients.ObjectiveOverall: to assess real-world effectiveness and safety of GH (Norditropin). This analysis: to compare clinical characteristics of GH-treated children in the United States and Europe.DesignThe American Norditropin Studies: Web-Enabled Research Program (ANSWER; 2002 to 2016, United States) and the NordiNet International Outcome Study (NordiNet IOS; 2006 to 2016, Europe) were multicenter longitudinal observational cohort studies.SettingData were recorded in 207 (United States) and 469 (Europe) clinics.ParticipantsPatients with GH deficiency, Turner syndrome, Noonan syndrome, idiopathic short stature, Prader-Willi syndrome, or born small for gestational age, who commenced GH treatment aged <18 years.InterventionGH was prescribed by treating physicians according to local practice.Main outcomes measuresBaseline data and drug doses were recorded. Data on effectiveness and safety were collected.ResultsANSWER had 19,847 patients in the full analysis set (FAS; patients with birthdate information and one or more GH prescription) and 12,660 in the effectiveness analysis set (EAS; GH-naive patients with valid baseline information). NordiNet IOS had 17,711 (FAS) and 11,967 (EAS). Boys accounted for 69% (ANSWER) and 57% (NordiNet IOS). Treatment start occurred later than optimal to improve growth. The proportion of boys treated was generally larger, children were older at treatment start, and GH doses were higher in the United States vs Europe. No new safety signals of concern were noted.ConclusionsIn most indications, more boys than girls were treated, and treatment started late. Earlier diagnosis of GH-related disorders is needed. The data support a favorable benefit-risk profile of GH therapy in children.
| S-EPMC6812718 | biostudies-literature
Project description:BackgroundQuality and safety issues are receiving growing attention. Patient safety culture (PSC) plays an important role in patient safety. The characteristics of PSC in various countries, each with a different set of values, have not been determined sufficiently. The aim of this study is to investigate the characteristics of PSC in Japan, Taiwan and the U.S.MethodsA cross-sectional survey was conducted in Japan and Taiwan using the Hospital Survey on PSC (HSOPS) questionnaire developed by the U.S. Agency for Healthcare Research and Quality (AHRQ). Data from Japan and Taiwan were also compared with the U.S. "2010 HSOPS Comparative Database" provided by AHRQ.ResultsValid response rates in Japan, Taiwan and the U.S. were 66.5% (6,963/10,466), 85.7% (10,019/11,692) and 35.2% (291,341/827,424), respectively. The proportion of respondents with some experience of event reporting during the past 12 months was highest in Japan. In general, U.S. healthcare workers were likely to evaluate their PSC higher than that in Japan or Taiwan. The attitude of continuous improvement in Japan and event reporting of near misses in Taiwan were rated as low. In the U.S., staffing was rated as high.ConclusionsThe results suggest that PSC varies among different countries, and the cultural setting of each country should be given special consideration in the development of effective intervention plans to improve PSC. Additional investigations with improved methodology and a common protocol are required to accurately compare PSCs among countries.
| S-EPMC3626628 | biostudies-literature
Project description:BackgroundWomen are underrepresented in human immunodeficiency virus (HIV) research in the United States. To determine if women screening for HIV clinical trials enrolled at lower rates than men, we performed a retrospective, cross-trial analysis.MethodsWe conducted an analysis of screening and enrollment during 2003-2013 to 31 clinical trials at 99 AIDS Clinical Trials Group network research sites in the United States. Random-effects meta regression estimated whether sex differences in not enrolling ("screen out") varied by various individual, trial, or site characteristics.ResultsOf 10 744 persons screened, 18.9% were women. The percentages of women and men who screened out were 27.9% and 26.5%, respectively (P = .19); this small difference did not significantly vary by race, ethnicity, or age group. Most common reasons for screening out were not meeting eligibility criteria (30-35%) and opting out (23%), and these did not differ by sex. Trial and research site characteristics associated with variable screen-out by sex included HIV research domain and type of hemoglobin eligibility criterion, but individual associations did not persist after adjustment for multiple testing.ConclusionsIn the absence of evidence of significantly higher trial screen-out for women, approaching more women to screen may increase female representation in HIV trials.
| S-EPMC7442845 | biostudies-literature
Project description:Background: The incidence and characteristics of gastric cancer have been shown to vary widely across Western and Eastern countries. Our study had two aims: to evaluate long-term trends in gastric adenocarcinoma in Japan over a period of 70 years, and to anticipate the future of gastric cancer in Japan, through comparison with data from the United States. Methods: Japanese patient data for 19,306 incident cases of gastric adenocarcinoma from 1946 - 2014 were collected from the Gastric Cancer Database at the Cancer Institute Hospital, Tokyo, Japan (CIH-GCDB). U.S. patient data for 78,625 incident cases of gastric cancer from 1973 - 2012 were obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. Changes over time in patient and tumor characteristics were investigated in these two cohorts. Results: There was a marked reduction of cancer incidence in the lower third of the stomach in the CIH-GCDB; over 70% to around 30%. The incidence in the upper third has been increasing steadily over time; 3% to 19%, although the number of cardia tumors has not changed. An increase in elderly and obese patients was also noted. In the U.S. population, there was a significant difference in the primary site across races. A notable overall increase in cardia cancer was evident in the Western population during the study period, with no similar change evident in the Japanese population over the last 15 years. In the East Asian population, the proportional frequency of tumors in the cardia was lower and that of tumors in the pyloric antrum was higher. Conclusion: In Japan, cancer in the antrum or pylorus of the stomach has been declining, whereas cancer in the body has been increasing. Unlike the Western population in the United States, adenocarcinoma of esophago-gastric junction is not increasing in Japan.
| S-EPMC5559953 | biostudies-literature
Project description:The coronavirus disease 2019 (COVID-19) pandemic has a major impact not only on public health and daily living, but also on clinical trials worldwide. To investigate the potential impact of the COVID-19 pandemic on the initiation of clinical trials, we have descriptively analyzed the longitudinal change in phase II and III interventional clinical trials initiated in Europe and in the United States. Based on the public clinical trial register EU Clinical Trials Register and clinicaltrials.gov, we conducted (i) a yearly comparison of the number of initiated trials from 2010 to 2020 and (ii) a monthly comparison from January 2020 to February 2021 of the number of initiated trials. The analyses indicate that the COVID-19 pandemic affected both the initiation of clinical trials overall and the initiation of non-COVID-19 trials. An increase in the overall numbers of clinical trials could be observed both in Europe and the United States in 2020 as compared with 2019. However, the number of non-COVID-19 trials initiated is reduced as compared with the previous decade, with a slightly larger relative decrease in the United States as compared to Europe. Additionally, the monthly trend for the initiation of non-COVID-19 trials differs between regions. In the United States, after a sharp decrease in April 2020, trial numbers reached the levels of 2019 from June 2020 onward. In Europe, the decrease was less pronounced, but trial numbers mainly remained below the 2019 average until February 2021.
| S-EPMC9015398 | biostudies-literature
Project description:BackgroundVorapaxar is a protease-activated receptor-1 antagonist approved by the U.S. Food and Drug Administration (FDA) for the reduction of thrombotic cardiovascular (CV) events in patients with a history of myocardial infarction (MI) and peripheral artery disease (PAD), without a previous stroke or transient ischemic attack (TIA).Methods and resultsWe examined the efficacy and safety of vorapaxar in the intended use population, considering 20,170 patients randomized in the multinational, double-blinded, placebo-controlled TRA 2°P-TIMI 50 trial. Of these, 16,897 qualified with a history of MI in the prior 2 weeks to 1 year and 3273 with PAD. At baseline 97% of the patients were treated with aspirin, 71% with a thienopyridine, and 93% a statin. At 3 years, the endpoint of CV death, MI, or stroke was significantly reduced with vorapaxar compared with placebo (7.9% versus 9.5%, HR, 0.80; 95% CI 0.73 to 0.89; P<0.001). Vorapaxar also significantly reduced the composite of CV death, MI, stroke, and urgent coronary revascularization (10.1% versus 11.8%, HR, 0.83; 95% CI 0.76 to 0.90; P<0.001), as well as the rate of CV death or MI (P<0.001). The safety endpoint of GUSTO moderate or severe bleeding, was increased in the vorapaxar group (3.7 versus 2.4, HR, 1.55; 95% CI 1.30 to 1.86, P<0.001). Intracranial bleeding (ICH) was 0.6% versus 0.4%, P=0.10 with vorapaxar versus placebo, with fatal bleeding 0.2% versus 0.2%; P=0.70.ConclusionsIn patients with prior MI or PAD who have not had a previous stroke or TIA, vorapaxar added to standard therapy is effective for long-term secondary prevention of thrombotic CV events, while increasing moderate or severe bleeding.Clinical trial registrationURL: clinicaltrials.gov Unique Identifier: NCT00526474.
| S-EPMC4392433 | biostudies-literature
Project description:BackgroundNVX-CoV2373 is an adjuvanted, recombinant spike protein nanoparticle vaccine that was shown to have clinical efficacy for the prevention of coronavirus disease 2019 (Covid-19) in phase 2b-3 trials in the United Kingdom and South Africa, but its efficacy had not yet been tested in North America.MethodsWe conducted a phase 3, randomized, observer-blinded, placebo-controlled trial in the United States and Mexico during the first half of 2021 to evaluate the efficacy and safety of NVX-CoV2373 in adults (≥18 years of age) who had not had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Participants were randomly assigned in a 2:1 ratio to receive two doses of NVX-CoV2373 or placebo 21 days apart. The primary objective was to determine vaccine efficacy against reverse-transcriptase-polymerase-chain-reaction-confirmed Covid-19 occurring at least 7 days after the second dose. Vaccine efficacy against moderate-to-severe disease and against different variants was also assessed.ResultsOf the 29,949 participants who underwent randomization between December 27, 2020, and February 18, 2021, a total of 29,582 (median age, 47 years; 12.6% ≥65 years of age) received at least one dose: 19,714 received vaccine and 9868 placebo. Over a period of 3 months, 77 cases of Covid-19 were noted - 14 among vaccine recipients and 63 among placebo recipients (vaccine efficacy, 90.4%; 95% confidence interval [CI], 82.9 to 94.6; P<0.001). Ten moderate and 4 severe cases occurred, all in placebo recipients, yielding vaccine efficacy against moderate-to-severe disease of 100% (95% CI, 87.0 to 100). Most sequenced viral genomes (48 of 61, 79%) were variants of concern or interest - largely B.1.1.7 (alpha) (31 of the 35 genomes for variants of concern, 89%). Vaccine efficacy against any variant of concern or interest was 92.6% (95% CI, 83.6 to 96.7). Reactogenicity was mostly mild to moderate and transient but was more frequent among NVX-CoV2373 recipients than among placebo recipients and was more frequent after the second dose than after the first dose.ConclusionsNVX-CoV2373 was safe and effective for the prevention of Covid-19. Most breakthrough cases were caused by contemporary variant strains. (Funded by Novavax and others; PREVENT-19 ClinicalTrials.gov number, NCT04611802.).
| S-EPMC8693692 | biostudies-literature
Project description:Pharmacogenomics, which is defined as the study of changes in the properties of DNA and RNA associated with drug response, enables the prediction of the efficacy and adverse effects of drugs based on patients’ specific genetic mutations. For the safe and effective use of drugs, it is important that pharmacogenomic information is easily accessible to clinical experts and patients. Therefore, we examined the pharmacogenomic information provided on drug labels in Korea, Europe, Japan, and the United States (US). The selection of drugs that include pharmacogenomic information was based on the drug list that includes genetic information from the Korea Ministry of Food and Drug Safety (MFDS) and US Food and Drug Administration (FDA) websites. Drug labels were retrieved from the sites of MFDS, FDA, European Medicines Agency, and Japanese Pharmaceuticals and Medical Devices Agency. Drugs were classified as per the Anatomical Therapeutic Chemical code, and the biomarkers, labeling sections, and necessity of genetic tests were determined. In total, 348 drugs were selected from 380 drugs with available pharmacogenomic information in Korea and the US after applying the inclusion and exclusion criteria. Of these drugs, 137, 324, 169, and 126 were with pharmacogenomics information in Korea, the US, Europe, and Japan, respectively. The most commonly represented drug class was antineoplastic and immunomodulating agents. Regarding the classification as per the mentioned biomarkers, the cytochrome P450 enzyme was the most frequently mentioned information, and the targeted anticancer drugs most commonly required genetic biomarker testing. The reasons for differences in drug labeling information based on country include differences in mutant alleles according to ethnicity, frequencies at which drug lists are updated, and pharmacogenomics-related guidelines. Clinical experts must continuously strive to identify and report mutations that can explain drug efficacy or side effects for safe drug use.
| S-EPMC10285385 | biostudies-literature
Project description:Regulatory authorities must balance ensuring evidence of efficacy and safety of new drugs. Various regulatory pathways, such as the accelerated approval program in the United States (US), allow authorities to quickly approve drugs for severely ill patients by granting market authorization based on surrogate end points and pending confirmatory trials. In this cross-sectional study, we considered 23 indications of cancer drugs that received accelerated approval by the US Food and Drug Administration (FDA) but were subsequently withdrawn as of April 2023. Our investigation extended to assessing the regulatory status of these accelerated approvals in the European Union (EU) and Japan, examining relevant regulatory documents and identifying factors contributing to the withdrawal in the United States. Comparing regions, we found that for 52% (12/23) and 30% (7/23) of withdrawn accelerated approvals in the United States, sponsors had also sought marketing authorization from the European Medicines Agency (EMA) and Japan's Pharmaceuticals and Medical Devices Agency (PMDA), respectively. As of the April 30, 2023 study cutoff date, 83% (10/12) of drug-indication pairs remained approved by the EMA, while the PMDA retained 100% (7/7). For these indications, the time from FDA withdrawal until the study cutoff date ranged from 0.23 years to 11.45 years for EMA approvals (median: 1.28 years) and 1.10 years to 11.45 years for PMDA approvals (median: 3.22 years). These findings highlight substantial regulatory discrepancies concerning cancer drugs with unconfirmed benefits. Addressing these discrepancies may involve requiring pharmaceutical companies to confirm clinical benefits using more robust end points and fostering international harmonization in regulators' assessment.
| S-EPMC11236735 | biostudies-literature
Project description:BackgroundThe Total Worker Health® (TWH) approach is a best practice method to protect and promote worker safety, health, and well-being. Central to this approach is leadership support and health and safety climates that support day-to-day use of health and safety policies and programs. There is some research that supports these relationships, but there is limited research amongst small businesses. Furthermore, it remains to be shown what role TWH business strategies, as reflected by organizational policies and programs, play in this process. The purpose of this study is to characterize small businesses by their organizations' TWH approach and assess the relationship of these approaches to employee health and safety behaviors.MethodsWe utilized cross-sectional data from 97 businesses participating in the Small+Safe+Well study. We collected data using a business assessment tool, Healthy Workplace Assessment™, and an employee assessment tool, Employee Health and Safety Culture Survey. We used latent profile analysis at the business level to identify subgroups of businesses based on a set of characteristics from these assessments. Linear regression analysis at the employee level was used to determine profile association with employee safety and health behaviors.ResultsThere were two profiles characterized by the lowest (33% of all businesses) and highest (9%) levels of the indicators. There were also two profiles with higher scores on two of the different foci on either TWH business strategies (27%) or leadership and climate (31%). Employees working for a business with a profile that focused on leadership and climate, in addition to having a business strategy, reported the best safety and health behaviors.ConclusionsOur study demonstrates that employee engagement in TWH will be highest when businesses have a strategy for how they implement a TWH approach and when they demonstrate leadership commitment to these strategies and foster positive safety and health climates. Our results offer suggestions on how to use TWH assessments to develop interventions for small businesses. More research is needed to understand whether small businesses can improve upon their profile overtime, whether these changes depend on contextual factors, and whether TWH interventions can help them improve their profile.
| S-EPMC8164062 | biostudies-literature