A instituição regulatória setorial e os arranjos contratuais em alianças para pesquisa clínica de medicamentos experimentais no Brasil

O setor farmacêutico, cujo investimento em atividade de P&D de novos medicamentos é determinante da competitividade, vive um contínuo processo de internacionalização de pesquisas, sobretudo por países emergentes. Por questões de estratégia de custo, know-how e eficiência, as indústrias farmacêuticas firmam alianças com as chamadas ORPCs – Organizações Representativas de Pesquisa Clínica, que são empresas especializadas em gestão de pesquisas clínicas (estudo de novos medicamentos conduzido em seres humanos), em um movimento de offshoring, para realizar atividades de gestão e monitoramento das pesquisas. Nesse cenário, destaca-se o Brasil que, de um lado, por possuir diversos fatores atrativos para a realização de pesquisas devido à sua quantidade e heterogeneidade populacional, tamanho do mercado e qualidade em pesquisa, vem crescendo no segmento de pesquisas clínicas. Por outro lado, as particularidades da regulação setorial do Brasil para pesquisa clínica caracterizam-na como ineficaz, morosa e desestimulante de investimentos. Diante desse quadro, o presente trabalho teve por objetivo investigar qual a relação entre a regulação setorial e os arranjos contratuais nessas alianças entre as indústrias e as ORPCs, ou seja, verificar de que forma se comportam contratualmente os agentes da aliança em face do formato da regulação do setor. Para tanto, adotou-se uma metodologia qualitativa exploratória, diante da escassez de estudos anteriores nesse sentido para esse setor, sob a estratégia de estudo de casos múltiplos. Foram estudadas 2 indústrias farmacêuticas, 2 ORPCs e ouvida também a percepção de outros agentes ligados ao segmento, como entidades associativas e o órgão de aprovação ética das pesquisas. Os dados foram coletados por entrevistas semiestruturadas e de documentos públicos como a legislação disponível. Aplicou-se análise temática categorial com uso de categorias definidas a priori e fez-se análise cruzada dos dados. Os resultados evidenciaram a relação entre as características da regulação setorial e o desenho dos arranjos contratuais, levando à reflexão de que a ineficiência do sistema regulatório impõe a adoção de mecanismos compensatórios das falhas institucionais para garantia das transações. Revelaram, nesse sentido, a insuficiência do sistema institucional na garantia das transações, induzindo à necessidade de expansão da teoria sob a perspectiva da Nova Economia Institucional e Economia dos Custos de Transação. Uma regulação burocrática, ineficaz, morosa e instável agrava a incerteza das transações e, consequentemente, estimula a adoção de mecanismos de coordenação entre as partes, contratual e extra contratualmente. Compreender o modo como os contratos podem ser arranjados e coordenados seguindo as características do ambiente institucional é importante, porque influi nas diferentes escolhas, ações e resultados para as organizações, justificando-se daí a relevância do assunto para o estudo estratégico.In the pharmaceutical industry, investments in R&D on new drugs are determinant of competitiveness and it is going through a continuous process of research internationalization, especially over emerging countries. Due to cost strategy, know-how and efficiency reasons, pharmaceutical companies have set alliances with CRO`s - Clinical Research Organizations, which are companies specializing in clinical trials management (study of new drugs conducted in humans) in an outsourcing movement, to perform management activities and monitoring of trials. In this context, Brazil, on one hand, is growing in the segment of clinical trials in virtue of its many attractive factors for the development of research such as population quantity and heterogeneity, market size and quality in research. On the other hand, particularities of the Brazilian sectoral regulation to clinical trials define it as an ineffective and lengthy system, discouraging investments. Given this situation, this study aimed to investigate the relationship between sectoral regulation and contractual arrangements in such alliances among industries and CRO’s, that is, verify how contractually agents behave in these alliances considering the format of sectoral regulation. Therefore, the study adopted an exploratory qualitative methodology, given the lack of previous similar studies for this industry, under the strategy of multiple case study. Two pharmaceutical companies and two CRO’s have been studied as well as heard the perception of other actors from the segment, such as associative entities and government ethical approval body. Data were collected by semi structured interviews and public documents as available legislation. Thematic categorical analysis was used by categories defined a priori, and then a cross-analysis of the data was applied. The results show the relationship between the characteristics of the sectoral regulation and the design of contractual arrangements, inducing to reflection that the inefficiency of the regulatory system requires the adoption of compensatory mechanisms to the institutional failures in transactions. They revealed in that sense the inadequacy of the institutional system in guarantee of transactions, leading to the need for expansion of the theory from the perspective of New Institutional Economics and Transaction Costs Economics. A bureaucratic, inefficient, lengthy and unstable regulation compounds the uncertainty of the transactions and stimulates the adoption of contractual and extra contractual coordination mechanisms between the parties. Understanding how contracts can be arranged and coordinated in accordance to the institutional environment characteristics is important as it influences the different decisions, actions and result for organizations, justifying hence its relevance for the strategic study.Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorFundo Mackenzie de Pesquis

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Alignment of the CMS silicon tracker during commissioning with cosmic rays

This is the Pre-print version of the Article. The official published version of the Paper can be accessed from the link below - Copyright @ 2010 IOPThe CMS silicon tracker, consisting of 1440 silicon pixel and 15 148 silicon strip detector modules, has been aligned using more than three million cosmic ray charged particles, with additional information from optical surveys. The positions of the modules were determined with respect to cosmic ray trajectories to an average precision of 3–4 microns RMS in the barrel and 3–14 microns RMS in the endcap in the most sensitive coordinate. The results have been validated by several studies, including laser beam cross-checks, track fit self-consistency, track residuals in overlapping module regions, and track parameter resolution, and are compared with predictions obtained from simulation. Correlated systematic effects have been investigated. The track parameter resolutions obtained with this alignment are close to the design performance.This work is supported by FMSR (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, and FAPESP (Brazil); MES (Bulgaria); CERN; CAS, MoST, and NSFC (China); COLCIENCIAS (Colombia); MSES (Croatia); RPF (Cyprus); Academy of Sciences and NICPB (Estonia); Academy of Finland, ME, and HIP (Finland); CEA and CNRS/IN2P3 (France); BMBF, DFG, and HGF (Germany); GSRT (Greece); OTKA and NKTH (Hungary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); NRF (Korea); LAS (Lithuania); CINVESTAV, CONACYT, SEP, and UASLP-FAI (Mexico); PAEC (Pakistan); SCSR (Poland); FCT (Portugal); JINR (Armenia, Belarus, Georgia, Ukraine, Uzbekistan); MST and MAE (Russia); MSTDS (Serbia); MICINN and CPAN (Spain); Swiss Funding Agencies (Switzerland); NSC (Taipei); TUBITAK and TAEK (Turkey); STFC (United Kingdom); DOE and NSF (USA)

Commissioning and performance of the CMS pixel tracker with cosmic ray muons

This is the Pre-print version of the Article. The official published verion of the Paper can be accessed from the link below - Copyright @ 2010 IOPThe pixel detector of the Compact Muon Solenoid experiment consists of three barrel layers and two disks for each endcap. The detector was installed in summer 2008, commissioned with charge injections, and operated in the 3.8 T magnetic field during cosmic ray data taking. This paper reports on the first running experience and presents results on the pixel tracker performance, which are found to be in line with the design specifications of this detector. The transverse impact parameter resolution measured in a sample of high momentum muons is 18 microns.This work is supported by FMSR (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, and FAPESP (Brazil); MES (Bulgaria); CERN; CAS, MoST, and NSFC (China); COLCIENCIAS (Colombia); MSES (Croatia); RPF (Cyprus); Academy of Sciences and NICPB (Estonia); Academy of Finland, ME, and HIP (Finland); CEA and CNRS/IN2P3 (France); BMBF, DFG, and HGF (Germany); GSRT (Greece); OTKA and NKTH (Hungary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); NRF (Korea); LAS (Lithuania); CINVESTAV, CONACYT, SEP, and UASLP-FAI (Mexico); PAEC (Pakistan); SCSR (Poland); FCT (Portugal); JINR (Armenia, Belarus, Georgia, Ukraine, Uzbekistan); MST and MAE (Russia); MSTDS (Serbia); MICINN and CPAN (Spain); Swiss Funding Agencies (Switzerland); NSC (Taipei); TUBITAK and TAEK (Turkey); STFC (United Kingdom); DOE and NSF (USA)

Performance of the CMS drift-tube chamber local trigger with cosmic rays

The performance of the Local Trigger based on the drift-tube system of the CMS experiment has been studied using muons from cosmic ray events collected during the commissioning of the detector in 2008. The properties of the system are extensively tested and compared with the simulation. The effect of the random arrival time of the cosmic rays on the trigger performance is reported, and the results are compared with the design expectations for proton-proton collisions and with previous measurements obtained with muon beams