Rest Of World Research Articles

Analysis on export competitiveness of oilseeds with BRICS countries

The paper attempts to assess India’s trade intensity as well as the revealed comparative advantage (RCA) of theoilseeds with respect to trade with BRICS (Brazil, Russia, India, China and South Africa) disaggregate levels. Thestudy assesses the structure of the comparative advantage from 2001 to 2018. The study found that TI (Trade Intensity) with the BRICS group was more in comparison to ROW (Rest of world). EEI (Export Intensity Index) for BRICS countries was also more intense in comparison to ROW whereas III (Import Intensity Index) showed less intense in comparison to ROW. Relative comparative advantage for groundnut, sesame and mustard was observed with the BRICS group.

Global Investigative Site Personnel Diversity and Its Relationship with Study Participant Diversity.

Background There is little to no empirical data on the race and ethnicity of the global community of professionals conducting clinical trials funded by pharmaceutical and biotechnology companies and little empirical evidence on the relationship between the race and ethnicity of investigative site personnel and the overall and corresponding diversity of participants enrolled.MethodsA global online survey conducted in mid-2021 gathered responses from 3462 clinical research professionals representing approximately 3300 distinct investigative sites.ResultsWorldwide, including all research settings, the majority (64%) of investigative site personnel are White, 20% are LatinX, 6% are Black, 7% are Asian and 3% are other races and ethnicities (e.g., indigenous peoples, Pacific Islander, Middle Eastern, etc.). The representation of non-white site personnel is significantly higher in North America and Rest of World (ROW) compared to Europe. The highest levels of personnel diversity are found in private community-based practices, investigative sites and site networks. A significant correlation (p < 0.001) was found between site personnel diversity and patient enrollment diversity worldwide. As the mix of site personnel by race and ethnicity increases, the diversity of patients enrolled—except for Asian patients in sites outside of North America—also increases. A significant relationship was also found between the proportion of a given race or ethnicity of investigative site personnel and the corresponding race and ethnicity of patients enrolled.ConclusionsAn opportunity exists to address under-representation in clinical trials through identifying, hiring and supporting investigative site personnel to best reflect the patient communities that they serve.

Analysis of racial and ethnic disparities in multiple myeloma US FDA drug approval trials

AbstractAfrican Americans (AAs) have a higher incidence of multiple myeloma (MM) than White patients. Mortality is also higher in AAs compared with White patients. AAs more commonly have immunoglobulin H translocations t(11;14) and t(14;16) compared with White patients. We sought to characterize the demographic representation in MM clinical trials and evaluate outcomes based on race and ethnicity. We conducted a pooled analysis of all trials submitted to the US Food and Drug Administration (FDA) to support approval of a MM therapeutic between 2006 and 2019. Demographic characteristics were analyzed descriptively. An age-adjusted stratified Cox regression model was used to evaluate the relationship between time-to-event outcomes and race and ethnicity. Nineteen global trials comprising 10 157 patients were pooled. White, Asian, and Black patients comprised 84%, 7%, and 4% of the dataset, respectively; Hispanic patients comprised 4%. The age-adjusted overall survival hazard ratio (HR) for Black compared with White patients was 0.89 (95% confidence interval [CI], 0.75-1.05). The age-adjusted HR for US Black vs US White patients was 0.82 (95% CI, 0.66-1.02). For rest-of-world (RoW) Black vs RoW White patients, the HR was 1.31 (95% CI, 0.97-1.77). Black and Hispanic patients were underrepresented in the trials supporting FDA approval of MM drugs. Black patients were primarily enrolled in the United States. Outcomes in US patients were more favorable compared with those in patients in the RoW. Given the higher incidence of MM in AAs and the different disease characteristics, efforts should be made to improve representation of AAs in MM clinical trials.

Spillover-feedback effects of social, economic, and environmental footprints based on the “Belt and Road Initiative”

The Belt and Road Initiative (BRI) links China to markets and sources of raw materials around the world while stimulating economic growth in developing countries and leading to widespread and occasionally unexpected social and environmental impacts. Considering that few studies have focused on the trade-embodied social and environmental impacts and two-way impact mechanisms throughout the BRI, this study, for the first time, uses social–economic–environmental footprints and the corresponding indicators of ecological efficiency and environmental stress to methodically measure the spatial distribution and regional transfer among three major regions comprising China (CHN), countries along the Belt and Road countries except China (CBR), and the rest of world (REW) from the standpoint of spillover and feedback effects, to better coordinate sustainable development between environment, economy, and society of the BRI. The results indicated the importance of spillover-feedback effects. Its significance lies not in comparison with the multiplier effect or the rates to TF, but in the indication of the two-way influence between regions through the numerical value of spillover–feedback effects of different regions and different industries. We identified that CBR and REW displayed the highest regional correlation in environment–economic aspects, followed by CHN and REW. The biggest contribution to the total footprint stemmed from the multiplier effects, suggesting the possibility that initiatives (e.g., BRI) could reduce the multiplier effects through internal drive optimization to offset the negative impact of spillover-feedback effects between regions (e.g., pollution transfer). Regarding employment, the feedback effects in CBR were the highest, suggesting that the indirect response due to the world's final demand pulled the largest employment in CBR. Moreover, REW was the net exporter of WF, CF, and EF, while the net importer of VAF and TOF. Furthermore, if ecological efficiency and environmental stress indicators were not considered, the stress of regional water resource use and carbon emission will be underestimated to a certain extent. For example, I-AGR of CHN and CBR in water resources stress, and III-HIS and V-EGW of CHN in carbon emissions stress. Finally, the proportions of different industries should be considered to evade misestimating the level of cleaner production in various industries during policymaking. Elucidating these mechanisms is essential to support decision-making that leads to sustainable development.

Spatial Price Transmission and Price Dynamics of Global Butter Export Market under Economic Shocks

Recently, the world has experienced striking economic and policy changes, and subsequent uncertainties have impacts on dairy trade price fluctuations. The Global Vector Autoregressive (GVAR) methodology was established in this paper to better understand international butter export prices transmission, the feedback between the economic context changes and price fluctuations, and the link between the global butter market, energy market, and other commodity markets. We assessed which key factors are typically associated with butter export price movements with regards to shocks to crude oil price, palm oil price, farm-gate raw milk price, exchange rates, and consumer price index (CPI) for food of the EU, New Zealand, the U.S., and the rest of world (RoW), respectively. Using generalized impulse response functions, this study found that decreases in farm-gate raw milk price could be swiftly transmitted to butter export prices of not only a home country but other foreign countries. However, palm oil price and crude oil price merely affects global butter export prices. We also found that U.S. dollar depreciations against the Euro will cause a decline in U.S. butter export price. It is concluded that butter export markets are not well-integrated, yet butter export prices of New Zealand and the U.S. are highly linked.

Whimsical (Waldenström's Macroglobulinemia Study Involving CArt-wheeL): Empowering Patients Internationally to Contribute Patient-Derived Data for Observational Research

IntroductionWaldenström's Macroglobulinemia (WM), a rare cancer with easily trackable disease parameters, is difficult to study in large trials. Patient-derived data are an attractive option to increase breadth of knowledge. The value of patient reported outcomes (PROs) is increasingly evident, with integration of electronic reporting of symptoms in cancer care shown to improve health outcomes and survival (Baasch, 2017).WM patients are well connected through the International Waldenström's Macroglobulinemia Foundation (IWMF) and its affiliates, using internet and social media. As a patient group, they are relatively well informed about their disease, its parameters (IgM, hemoglobin) and available treatments.This study utilised www.cart-wheel.org, an ethically-approved online rare cancer database for patient-derived data, and the digital connectedness of WM patients to develop a continuously expanding patient-derived dataset, providing foundation for hypothesis generation around WM PROs and improving our understanding of this rare disease.MethodsAn ethics committee-approved WM-specific extension to www.cart-wheel.org's questionnaire, developed by clinician and patient investigators, went online June 2016. Participants complete an online consent form and provide data on symptoms, pathology results, treatments, their tolerance and how they were accessed. Following development of online consent and demonstration of feasibility with Australian recruitment, international promotion by the IWMF was undertaken through utilisation of multiple social media platforms, including online discussion forums, Facebook, email mailing lists and community newsletters. Patients are encouraged to print out their personal www.cart-wheel.org report and review any missing data with their clinician. Data analysis will be conducted utilising independent samples t-test, cross-tabulation and Pearson Chi-squared.ResultsThe local recruitment drive demonstrated initial project feasibility with 69 participants. Following international promotion in May 2017, 137 further participants were recruited in 10 weeks. The 206 participants were predominantly from USA (45%), Australia and New Zealand (30%), Canada (10%), UK (7%) and Netherlands (4%), with median age 67 years (43-85) and male predominance (62%). Median age at diagnosis was 60 (41-83) with 22 (11%) diagnosed under 50 years of age. Of the 123 (60%) patients who provided symptom data at diagnosis, fatigue was most common (56%), correlating with median hemoglobin 11.1 g/dL (5.2-12.9 g/dL, n=39) compared to 12.4 g/dL (4.4-15.4 g/dL, n=44) in those without fatigue (p=0.005), and trend to higher IgM (median IgM 3410 mg/dL, non-fatigued 2875 mg/dL, p=0.33). Other common symptoms were B-symptoms (entered as weight loss >10%, fever or night sweats, 28%), peripheral neuropathy (documented specifically or as numbness/tingling, 28%), leg cramps (15%) and epistaxis (nose bleeding, 14%). Median IgM at diagnosis was 3190 mg/dL (30-10300 mg/dL, n=79) and hemoglobin 11.6 g/dL (4.4-16.6 g/dL, n=86), whereas at first treatment, medians were 3814 mg/dL (50-6800 mg/dL, n=58) and 10.2 g/dL (4.4-15.4 g/dL, n=64), respectively (p=0.27 and p=0.003, respectively). Thirty-two different first-line therapeutic combinations were documented by 125 participants. From diagnosis, median time to first treatment was 82 days (0-8803 days, n=119), with median time for USA patients being 59.5 days (0-8803, n=54) and Rest of World (ROW) patients 106 days (0-5765, n=66), (p=0.23). Treatment access data was available for 121 (91%) of 133 therapies provided by USA patients, with 32 (26%) therapies government funded, whereas in ROW patients, access data was available for 120 (85%) of 141 therapies, 69 (58%) being government funded.ConclusionThis study demonstrates a robust data-collection platform via www.cart-wheel.org and the feasibility of its use globally for WM patient-derived data. Upon further recruitment and encouragement of more complete and continuous data entry, an expanding and increasingly robust body of data will increase knowledge of the range of presentations and treatment experiences of WM patients. Future graduated database additions will include validated PROs (e.g. EuroQol EQ-5D-5L). WhiMSICAL has the potential to map real-world therapeutic efficacy, along with international patterns of treatment access. DisclosuresTohidi-Esfahani:Janssen Cilag: Other: Funding facilitating research paid to third party (BioGrid Australia). Warden:Janssen Cilag: Other: Funding facilitating research paid to third party (BioGrid Australia). D'Sa:Janssen Cilag: Consultancy, Honoraria, Other: Education grant, Research Funding; Amgen: Consultancy, Honoraria, Research Funding. Kersten:Kite Pharma: Honoraria; Novartis Pharmaceuticals Corporation: Honoraria; MSD: Honoraria; BMS: Honoraria; Gilead Sciences: Honoraria; Mundipharma: Honoraria; Milennium/Takeda: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Amgen: Honoraria. Ysebaert:Janssen: Consultancy, Research Funding, Speakers Bureau. Thomas:Celgene: Research Funding; Bristol Myers Squibb: Research Funding. Tam:Roche: Honoraria, Research Funding; Janssen Cilag: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding. Harrington:Abbvie: Equity Ownership; Gilead: Equity Ownership. Trotman:Celgene: Membership on an entity's Board of Directors or advisory committees, Other: Funding facilitating research paid to third parties. All positions non-remunerated; Roche: Membership on an entity's Board of Directors or advisory committees, Other: All positions non-remunerated, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Position non-remunerated; Janssen Cilag: Membership on an entity's Board of Directors or advisory committees, Other: Funding facilitating research paid to third parties. All positions non-remunerated, Speakers Bureau.

The Use of Subgroup Disproportionality Analyses to Explore the Sensitivity of a Global Database of Individual Case Safety Reports to Known Pharmacogenomic Risk Variants Common in Japan.

IntroductionGenetic variations of enzymes that affect the pharmacokinetics and hence effects of medications differ between ethnicities, resulting in variation in the risk of adverse drug reactions (ADR) between different populations. Previous work has demonstrated that risk-group considerations can be incorporated into approaches of statistical signal detection. It is unknown whether databases of individual case safety reports (ICSRs) are sensitive to pharmacogenomic differences between populations.ObjectiveThe aim of this study was to explore the sensitivity of a global database of ICSRs to known pharmacogenomic risk variants common in Japan.MethodsThe data source was VigiBase, the global database of ICSRs, including all reports entered in the version frozen on 5 January 2020. Subgroup disproportionality analysis was used to compare ICSRs of two subgroups, Japan and rest of world (RoW). Reports for UGT1A1-metabolized irinotecan and the CYP2C19-metabolized drugs voriconazole, escitalopram and clopidogrel were selected for comparison between the subgroups based upon known genetic polymorphisms with high prevalence in Japan. Contrast between the subgroups was quantified by IC delta ({mathrm{IC}}_{Delta }), a robust shrinkage observed-to-expected (OE) ratio on a log scale. Harmonic mean p values (HMP) were calculated for each drug to evaluate whether a list of pre-specified ADRs were collectively significantly over- (or under-)reported as hypothesized. Daily drug dosages were calculated for ICSRs with sufficient information, and dose distributions were compared between Japan and RoW and related to differences in regionally approved doses.ResultsThe predictions of over-reporting patterns for specific ADRs were observed and confirmed in bootstrap HMP analyses (p = 0.004 for irinotecan and p < 0.001 for each of voriconazole, escitalopram and clopidogrel) and compared with similar drugs with different metabolic pathways. The impact of proactive regulatory action, such as recommended dosing and therapeutic drug monitoring (TDM), was also observable within the global database. For irinotecan and escitalopram, there was evidence of use of lower dosages as recommended in the Japanese labels; for voriconazole, there was evidence of use of TDM with an over-reporting of terms related to drug level measurements and an under-reporting of liver toxicity.ConclusionsPharmaco-ethnic vulnerabilities caused by pharmacogenomic differences between populations may contribute to differences in ADR reporting between countries in a global database of ICSRs. Regional analyses within a global database can inform on the effectiveness of local risk minimization measures and should be leveraged to catalyse the conversion of real-world usage into safer use of drugs in ethnically tailored ways.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40264-021-01063-1.

Whimsical (Waldenstrom's Macroglobulinemia Study Involving CArt-wheeL): A Global Patient-Derived Data Registry Capturing Treatment, Quality of Life and COVID-19 Data

Whimsical (Waldenstrom's Macroglobulinemia Study Involving CArt-wheeL): A Global Patient-Derived Data Registry Capturing Treatment, Quality of Life and COVID-19 Data

A welfare analysis of China's tariffs on U.S. hardwood products

China has been the top importer of U.S. log and lumber since 2010. With the ongoing trade disputes between the U.S. and its trading partners, especially with China, it is of great interest to assess the potential impacts of different trade interventions on U.S. forest sector. In this study, we focus on hypothetical uniform tariffs by China on U.S. hardwood products in four scenarios: tariffs imposed on log, lumber, and veneer, respectively, and on these products altogether. With an emphasis on U.S. timberland owners as log producers, a two-stage partial equilibrium displacement model is applied to measure the vertical linkage between log and its secondary products, lumber and veneer, as well as the horizontal linkage between lumber and veneer. Assuming a 25% uniform tariff, our results show that the welfare effects on stakeholders in four scenarios highly differ but U.S. timberland owners suffer substantial welfare loss as a whole in all scenarios. U.S. consumers of lumber and veneer, on the contrary, benefit from China's uniform tariffs in general. The total of China's consumer surplus is negative with its import tariffs on log, lumber, and all three products. Vertical and horizontal linkages within the U.S. hardwood sector are confirmed in all scenarios. Lastly, trade deflection effect is captured as the U.S. would export more hardwood products to the rest of world (ROW), resulting in positive but small changes in consumer surplus in the ROW, in all scenarios.

Efficacy and safety of paliperidone palmitate 3-month formulation in Latin American patients with schizophrenia: A subgroup analysis of data from two large phase 3 randomized, double-blind studies.

Objective:To analyze the efficacy and safety of paliperidone palmitate 3-monthly (PP3M) in Latin American patients with schizophrenia vs. rest-of-world (ROW).Methods:We analyzed data from two multinational, double-blind (DB), randomized, controlled phase 3 studies including patients with schizophrenia (DSM-IV-TR) previously stabilized on PP1M/PP3M (open-label [OL] phase). Patients were randomized to PP3M or PP1M (noninferiority study A) and PP3M or placebo (study B) in DB phase. The subgroup analysis included Latin American (Argentina, Brazil, Colombia, Mexico) patients. Primary efficacy endpoints were relapse-free rates (study A) and time-to-relapse (study B).Results:In study A, 63/71 (88.7%) and in study B 38/43 (88.4%) Latin American patients completed the DB phase. In study A, relapse-free percentage was similar in Latin America (PP3M: 97%, PP1M: 100%) and ROW (PP3M: 91%, PP1M: 89%). In study B, median time-to-relapse was not estimable in the Latin American subgroup for either placebo or PP3M groups, nor for the ROW PP3M group; the median time-to-relapse in the ROW placebo group was 395 days. Caregiver burden improved in patients switching from oral antipsychotics (OL baseline) to PP3M/PP1M in DB phase (Involvement Evaluation Questionnaire score mean ± SD change, -9.4±15.16; p < 0.001). Treatment emergent adverse events with PP3M during DB phase were similar in Latin America (study A: 24/34 [70.6%]; study B: 15/21 [71.4%]) and ROW (study A: 318/470 [67.7%]; study B: 84/139 [60.4%]) subgroups.Conclusion:PP3M was efficacious and showed no new safety concerns in patients with schizophrenia from Latin America, corroborating ROW findings.Clinical trial registration:NCT01515423, NCT01529515

PF495 WHIMSICAL (WALDENSTRÖM'S MACROGLOBULINEMIA STUDY INVOLVING CART‐WHEEL): A GLOBAL PATIENT‐DERIVED DATA REGISTRY MAPPING TREATMENT AND QUALITY OF LIFE DATA

Background:Patient‐derived data can increase breadth of knowledge in rare cancers like Waldenström's Macroglobulinemia (WM), including Patient‐reported outcomes (PROs).Aims:This study utilised www.cart‐wheel.org, an ethically‐approved online rare cancer database for patient‐derived data, and harnessed the digital connectedness of WM patients globally, to develop a continuously expanding dataset and platform for hypothesis generation around WM.Methods:An ethics committee‐approved WM‐specific extension to the www.cart‐wheel.org questionnaire, developed by clinician and patient investigators, was released June 2016. Participants complete consent online and enter their symptom, pathology and treatment data. Recruitment strategies driven by the International Waldenström's Macroglobulinemia Foundation investigators utilised multiple social media platforms. Inclusion of the EORTC‐QLQ‐C30 quality of life (QoL) questionnaire went live in October 2018, with targeted recruitment messaging sent out in February 2019.Results:355 patients from 17 countries have been recruited, predominantly from USA (48%) and Australia (22%), with male predominance (62%). Median age at diagnosis was 61 (range 24–83), median IgM 27.4 g/L (IQR 13.1–40.3 g/L, n = 130) and median hemoglobin 112 g/L (IQR 97–128 g/L, n = 134). Of the 279 (79%) patients providing symptoms at diagnosis, fatigue/muscle weakness was most common (45%) and 32% were asymptomatic. Using the Impact of Event Scale for symptoms of post‐traumatic stress disorder (PTSD) resulting from a cancer diagnosis, at median 50 months post‐diagnosis, the mean score among 305 patients was 5.8 (no stress = 0, maximal stress = 24), with 29/305 (10%) scoring ≥13 (PPV 94% for PTSD, Thoresen et al, 2010). 41 different first‐line therapeutic combinations were documented by 238 patients. Median time from diagnosis to first treatment for USA patients was 50 days (IQR 15–423, n = 104) vs Rest of World (ROW) 170 days (IQR 22–775, n = 120), (p = 0.06). Of the 213 therapies listed by 108 USA patients, 59 (28%) were reported as accessed by government or public program and 8 (4%) via clinical trial participation, whereas among ROW patients (n = 113), 122/225 (54%) were government/public program accessed and 31/225 (14%) through clinical trials (p = 0.0001 and p = 0.0002, respectively). In the three weeks following targeted messaging, 156 patients responded to the QoL questions. Early analysis of raw scores for overall health (Q29) and overall quality of life (Q30), ranging from 1: very poor to 7: excellent, demonstrated means of 5.1 and 5.8, respectively. Respondents who received BTK inhibitors (BTKi, n = 33) had comparable Q29 and Q30 scores compared to those who received non‐BTKi treatment (n = 84): Q29 means 5.8 vs 5.5, Q30 6.1 vs 5.7 (p = 0.2 and p = 0.13, respectively). This was despite median 2 (IQR 1–4) lines of treatment in the BTKi group compared to median 1 (IQR 1–2) in the non‐BTKi group.Summary/Conclusion:The WhiMSICAL study is a robust global patient‐derived data platform, providing insight into patient symptoms, including WM‐related stress responses, diversity of therapies and QoL. Further recruitment (Project 1000) and encouragement of more complete and continuous data entry will increase the utility of WhiMSICAL. As an expanding and increasingly reliable body of data, WhiMSICAL has the potential to map real‐world PROs, and provide a scientific and ethically‐approved portal for patients’ voices globally.

SUN-255 PATRO Children, a Multi-Center, Non-Interventional Study of the Long-Term Safety and Efficacy of Omnitrope® in Children Requiring Growth Hormone Treatment: Comparing United States (US) and Rest of World (ROW) Data

Introduction: PATRO Children is a non-interventional, international, longitudinal study of the long-term safety of a recombinant human growth hormone (rhGH; Omnitrope®, Sandoz) in patients requiring this therapy. Here we compare data from participants in the US with the ROW. Methods: The study population includes infants, children and adolescents receiving Omnitrope® therapy according to local prescribing information. All adverse events (AEs) are monitored and recorded for evaluation of rhGH safety. Laboratory values (including glucose metabolism and anti-hGH antibodies) are requested at least once a year. Height standard deviation score (HSDS), height velocity (HV) and HVSDS are calculated using height measurements and country-specific reference tables to evaluate rhGH efficacy. Results: As of September 2018, 294 US patients (including 65.6% GHD, 21.1% ISS, 2.7% SGA) and 6500 ROW patients (including 57.9% GHD, 25.8% SGA, 3.0% ISS) had been enrolled in the study. Mean (± standard deviation [SD]) age at enrollment was 10.44 ± 3.64 years for US patients and 72.8% were male. For ROW, mean ± SD age at enrollment was 8.95 ± 3.90 years and 58.7% were male. Overall, 53.1% (US) and 86.3% (ROW) of patients were rhGH naïve. Mean ± SD Omnitrope® treatment duration was 40.24 ± 17.39 and 38.18 ± 26.89 months in US and ROW patients, respectively; 49.66% (US) and 42.35% (ROW) of patients had completed 3 years’ treatment. Mean ± SD doses at study baseline and after 3 years were 0.0473 ± 0.0144 and 0.0541 ± 0.0289 mg/kg/day in the US group, and 0.0321 (0.0094) and 0.0359 (0.0106) mg/kg/day in the ROW group. In total, 886 AEs were recorded in 194 (66.0%) US patients; 5 AEs in 5 patients were considered treatment-related, and 3 (1.3%) patients discontinued therapy due to an AE. For ROW, 11716 AEs were recorded in 2977 (48.0%) patients, 636 (452 patients) of which were considered treatment-related; 105 (1.7%) discontinued due to an AE. Serious AEs were noted in 14 (4.8%) US patients (19 events) and 738 (11.9%) ROW patients (1429 events). No clinically relevant positive anti-hGH antibody titers have been found after the start of rhGH therapy in patients tested so far. After 3 years, improvement from baseline in HSDS and HVSDS among prepubertal, treatment-naïve GHD patients was similar between the US (+1.34; +3.06) and ROW (+1.35; +3.55) groups. Conclusions: Based on this snapshot of data from the ongoing PATRO Children study, Omnitrope® treatment appears to be similarly well tolerated and effective in patients enrolled from the US and ROW. Some differences between the US and ROW patients are apparent, likely reflecting differences in referral patterns, rhGH treatment practices and approved indications across different regions.

Economic Impact of the United States withdrawal from Trans-Pacific Partnership on Canada: A Computable General Equilibrium Based Analysis

Canada has recently concluded negotiations on Trans-Pacific Partnership (TPP) with 11 major Pacific Rim countries. The TPP would have a potential economic impact on its member countries (including Canada). In spite of the United States (U.S.) withdrawal from the TPP region, one may expect the agreement to still have an impact on the Canadian economy through changing trade dynamics with currently closed and large trading partners, such as Japan. In this study, we built a Computable General Equilibrium (CGE) model based on the Global Trade Analysis Project (GTAP) model and database to assess the economic impact of the U.S. withdrawal from TPP agreement on the Canadian economy. Our model included 13 regions, 15 sectors, and three factors of production. Three scenarios were simulated to capture the economic impact of the U.S. withdrawal from TPP on Canada: (i) Baseline scenario, where we developed a growth projection model to simulate the economic and trade growth in 2030 without the TPP. (ii) In the second scenario, TPP12 scenario, we assumed that the TPP would be fully implemented by 2030. (iii) In the third scenario, TPP11, we assumed that U.S. had withdrawn from the TPP and the other 11 country members (including Canada) do business in spite of it. The study showed that both TPP12 and TPP11 will generate long-term economic gains for Canada. If the TPP is fully implemented in the absence of the U.S. (Scenario TPP11), the impact on Canada will be similar to TPP12 scenario, although it will generate major trade diversion from the U.S. toward other TPP member countries. Total Canadian imports and exports are projected to decrease by 0.26 (1.6 billion USD) and 0.35 (2.7 billion USD) percent, respectively. This net change is a combination of trade creation with TPP11 region and Rest of World (RoW) and diversion of trade flows from the U.S.

Insulin Injection Technique in China Compared with the Rest of the World.

IntroductionApproximately 9 million people in China use insulin but little is known of their injection techniques (IT). Our aim was to understand IT in China via direct examination and a detailed survey.MethodsInjection Technique Questionnaire (ITQ) results of 3853 patients from 20 representative centers in China were compared with the Rest of World (ROW).ResultsInsulin pens are used by 92% of Chinese insulin injectors, with > 3/4 using 4- or 5-mm pen needles. This is consistent with Chinese BMI values (and thus subcutaneous fat thickness) being lower than in ROW, raising the risk of IM (intramuscular) injections with longer needles. Total daily insulin dose is ~ 33 IU in China vs. 45 IU elsewhere. Lipohypertrophy (LH) rates are lower than in ROW, but still found in at least 25% of Chinese patients. Patients apparently do not realize they have LH or are unaware of the hazards of injecting into LH since many of them do so, and those who do use a mean of 11 IU more of insulin than non-LH patients. This incremental insulin use possibly costs the Chinese health care service around 2 billion RMB annually. Needle reuse is also frequent in China (78% vs. 48% ROW), and the high cost of pen needles is the main reason patients cite for reusing (25% use a single needle > 10×).ConclusionThis study reveals many areas in which Chinese professionals and patients can optimize injection practices and thereby improve outcomes and reduce costs. The official guidelines of the Chinese Diabetes Society, based on the FITTER recommendations, offer a roadmap for reaching this goal.FundingBD Diabetes Care.Plain Language SummaryPlain language summary available for this article.

THUR 171 Natalizumab effectiveness and safety in top uk patients

IntroductionThe TYSABRI® Observational Program (TOP) is an ongoing, global open-label study enrolling natalizumab-treated relapsing-remitting multiple sclerosis patients in real-world settings. Country-specific data can provide information on natalizumab’s benefit-risk in local clinical practice.MethodsClinical outcomes in UK and rest of world (ROW) TOP patients were compared.ResultsAs of May 2016, 134 UK and 5793 ROW patients were enrolled in TOP. Mean baseline Expanded Disability Status Scale (EDSS) score was 4.27 in the UK and 3.45 in ROW. Mean years on natalizumab was 3.52 in the UK and 3.04 in ROW. Annualized relapse rate (ARR) decreased by 89.7% (from 2.21 pre-natalizumab to 0.23 post natalizumab initiation; p&lt;0.0001) in the UK and by 89.0% (from 1.99 to 0.22; p&lt;0.0001) in ROW. In both cohorts, ARR decrease by baseline EDSS score was 91.0%–93.2% for &lt;3.0 and 87.3%–88.9% for ≥3.0; mean EDSS score change from baseline over 6 years was &lt;1.0. Overall, 9 of 134 UK patients (6.7%) experienced ≥1 serious adverse event.ConclusionsNatalizumab demonstrated similar effectiveness in the UK and ROW cohorts. Safety in the UK cohort was consistent with natalizumab’s established safety profile.SupportBiogenDisclosuresRN: grant/travel support from Biogen; KR, SL, SFSF, CS: Biogen employees.

Ex-Ante Analysis of Economic, Social and Environmental Impacts of Large-Scale Renewable and Nuclear Energy Targets for Global Electricity Generation by 2030

This study assesses the economic, social and environmental impacts of renewable and nuclear energy targets for global electricity generation by 2030. It examines different regions, as they might experience different impacts depending on the structures of their economies and their local natural resources, to understand the impact of these targets on their economics and well-being of their people. These regions are: Saudi Arabia, the United States (US), China, India, Europe and Rest of World (ROW). A well-known Computable General Equilibrium (CGE) model, the Global Trade Analysis Project (GTAP), is modified and used to predict global economic shifts that would be triggered by two scenarios. The business as usual (BAU) scenario assumes that the current electricity mix remains unchanged until 2030. The Renewable and Nuclear Energy (RNE) scenario is based on the International Energy Outlook (IEO) 2016 prediction. The analysis shows that the GDP value of all regions, except India, is affected negatively. The study shows a loss of 4.45 million jobs worldwide in the RNE compared to the BAU. Finally, the implementation of planned renewable and nuclear energy slightly benefits the environment but not enough to mitigate rise in global temperature.

Turkish Insulin Injection Technique Study: Population Characteristics of Turkish Patients with Diabetes Who Inject Insulin and Details of Their Injection Practices as Assessed by Survey Questionnaire.

IntroductionOver 7 million people in Turkey have diabetes. Of the 1 million who inject insulin little is known of their habits and injection techniques.MethodsWe conducted an Injection Technique Questionnaire (ITQ) survey throughout Turkey that involved 1376 patients from 56 centers. Turkish values were compared with those from 41 other countries participating in the ITQ, known here as Rest of World (ROW).ResultsThe majority (50.4%) of Turkish insulin users give four injections/ day as opposed to ROW, where only 30.9% do. The abdomen is the most common injection site used by Turkish patients, but they also inject insulin in multiple body sites more often than do patients in ROW. Body mass index values in Turkey were 0.75 units higher than those in ROW as was the mean total daily dose (average daily dose [ADD]) of insulin (54.0 IU in Turkey vs. 47.4 IU in ROW). Mean glycated hemoglobin (HbA1c) in Turkey was 9.1%, which is higher than in ROW and possibly related to the higher BMI and ADD. Turkish patients use insulin analogs (short and long-acting) more frequently than do patients in ROW. The shortest pen needles (4 mm) are used by about one-third of patients in Turkey, but the longer ones (8 mm) are equally common. Needles are reused in Turkey at a rate of 3.4 injections/single needle. However, needle reuse, whether with pens or syringes, is lower in Turkey than ROW, as is the number of times a reused needle is used. More than 75% of used sharps in Turkey go into the rubbish, with nearly 6% having no protection of the tip.ConclusionThe continued use of 8-mm needles raises the risk of intramuscular injections in Turkish patients. Despite full reimbursement, needle reuse still remains an important issue. More focus needs to be given to dwell times under the skin, reconstitution of cloudy insulant, correct use of skin folds and safe disposal of sharps.FundingBD Diabetes Care.

Turkish Insulin Injection Techniques Study: Complications of Injecting Insulin Among Turkish Patients with Diabetes, Education They Received, and the Role of Health Care Professional as Assessed by Survey Questionnaire.

IntroductionUsing the Turkish and rest of world (ROW) Injection Technique Questionnaire (ITQ) data we address key insulin injection complications.MethodsSummarized in first ITQ paper.ResultsNearly one-third of Turkish insulin users described lesions consistent with lipohypertrophy (LH) at their injection sites and 27.4% were found to have LH by the examining nurse (using visual inspection and palpation). LH lesions in the abdomen and thigh of Turkish patients are slightly smaller than those measured in ROW but more than half of Turkish patients who have LH continue to inject into them at least daily. More than a quarter of Turkish patients have frequent unexplained hypoglycemia and nearly 2 out of 5 have glycemic variability, both of which have been linked to the presence of LH and the habit of injecting into it. Nearly half of Turkish injectors report having pain on injection. Of these, just over half report having painful injections only several times a month or year (i.e., not with every injection). In Turkey the diabetes nurse has by far the major role in teaching patients how to inject. Nearly 40% of Turkish injectors get their sites checked at least annually, and a larger proportion than ROW had received recent (within the last 12 months) instruction on how to inject properly.ConclusionTurkish patients and professionals have clearly made progress in injection technique, but there are still considerable challenges ahead which the new Turkish guidelines will help address.FundingBD Diabetes Care.

Phase III study of aldoxorubicin vs investigators' choice as treatment for relapsed/refractory soft tissue sarcomas.

11000 Background: Aldoxorubicin (A) is a novel drug that binds covalently to albumin in the circulation, accumulates in tumors and releases doxorubicin in the acidic tumor environment. It has demonstrated enhanced antitumor activity in several murine models and in a phase IIb STS study when compared with doxorubicin. Trial Design: Phase III open-label study evaluating efficacy and safety of A compared to investigators' choice (IC) of treatment in subjects with soft tissue sarcomas (STS) who have relapsed or were refractory to prior chemotherapy. Objectives: (1) Primary: Efficacy of A vs IC: progression-free survival (PFS); (2) Secondary: Efficacy of A vs IC: tumor response (ORR), disease control rate (DCR; CR+PR+SD &gt; 4 months), overall survival (OS) and safety. Methods: A: 350 mg/m2 (260 mg/m2dox. equiv.) iv q3 wks. IC drugs: dacarbazine, doxorubicin, pazopanib, ifosfamide, gemcitabine/docetaxel administered per package insert or study site's standard practice; provided, with G-CSF, by the sponsor. AEs, serum chemistries, CBCs, EKG and ECHOs obtained frequently. CT scans every 6 weeks for 30 weeks, then every 12 weeks; analyzed using RECIST 1.1 by Blinded Independent Central Review. Results: Randomized 433 subjects; 79 countries; 313 (72%) in North America (NA) and 121 (28%) in Rest of World (ROW). Leiomyosarcoma 42.5%, liposarcoma 15%, synovial sarcoma 9%, others 33.5%, L-sarcomas (lipo+leiomyo) 57.5%. Median PFS Total Pop. (months): A= 4.06; IC= 2.96; p = 0.12; HR = 0.82 (0.64-1.06). Median PFS NA (months): A= 4.21; IC= 2.96; p = 0.027; HR = 0.71 (0.53-0.97). Median PFS L-sarcomas (months): A= 5.32; IC= 2.96; p = 0.007; HR = 0.62 (0.44-0.88). DCR Total Pop.(%): A= 30.3; IC= 20.9; p = 0.028; DCR NA (%): A= 32.9; IC= 19.2; p = 0.007; DCR L-Sarcomas (%): A= 37.5; IC= 23.0; p = 0.018. ORR and OS will be reported. TEAEs gr 3 or 4 (%): A= 61.0; IC= 46.4. Trtmt Rel. SAEs (%): A= 27.0; IC= 14.0. TEAEs leading to Drug Discontinue (%): A= 4.2; IC= 6.3. Trtmt Related Deaths (#); A= 3; IC= 0; LVEF &lt; 50% expected (%): A= 2.8%;Dox = 12.8%. Conclusions: Aldox is an active, well-tolerated drug for treating relapsed or refractory STS and is significantly better than standard treatments for patients with L-sarcomas. Clinical trial information: NCT02049905.

Indian Injection Technique Study: Population Characteristics and Injection Practices.

IntroductionIt was estimated that 3.2 million Indians with diabetes injected insulin in 2010, but little is known about the techniques used.MethodsIn 2015 we conducted an injection technique questionnaire (ITQ) survey throughout India involving 1011 patients. Indian values were compared with those from 41 other countries participating in the ITQ, known here as rest of world (ROW).ResultsMean HbA1c was 8.6. BMI values in India were 1.5–3 units lower than in ROW depending on patient group, meaning the risk of intramuscular (IM) injections is high in India. The mean total daily dose (TDD) of insulin was lower in every category of Indian patient than in ROW, perhaps reflecting the lower BMI. Needle reuse, whether with pens or syringes, is much higher in India than ROW and so is the number of times the needle is used. The majority (56.8%) of Indian insulin users performed only 2 injections/day as opposed to ROW where 45% of patients performed at least 4 injections/day. Indian patients inject insulin in the thighs more often than patients in ROW, a site where IM injections are more risky. Many patients do not have proper access to sharps containers or have other risk factors that could lead to blood-borne pathogen spread. More than 60% of used sharps in India go into the rubbish, with nearly 12% not even having the minimum protection of a cap.DiscussionThe shortest needles are very common in India; however, the level of needle reuse is high. Multiple daily injections therapy is not as common in India as ROW. More focus needs to be given to dwell times under the skin, reconstitution of cloudy insulins, skinfolds, and safe sharps disposal.