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Cooperation among a diverse group of stakeholders, including: research, sponsors industry, academia, government, nonprofit organizations, clinical investigators, patients, physicians, and regulators is necessary in conducting a clinical trial today. The investigators and sites where clinical studies are conducted, should be able to manage it all those things, so they can conduct clinical studies to ensure the accuracy and quality of data as well the safety of research subjects. In pursuit of continuous improvement of an organization's performance, Theory of Constraints operates through management actions on bottlenecks, with tools that can assist in the understanding of a complex problem, among them is the Current Reality Tree (CRT). It is important to make a diagnosis of the organization's internal environment, and before the changes and effectively interventions in organizations. Finding a problem leads to the identification of an opportunity to improve process. The aim of this study is to verify if the Current Reality Tree can assist the management of a clinical research site, since it is a complex problem, pointing out opportunities for improvement. For this, we conducted a study case in the Clinical Research Unit (UPC) HCFMRP-USP, being applied all steps from CRT methodology. As a result, it was built ARA, identified 257 Undesirable Effects (EIs) and 04 root causes of these effects, which together are the core problems. For each of the root causes was proposed a plan of action. With this it has been concluded that the use of the ARA was efficient under clinical research, one could summarize the main opportunities for improvement of a site, and direct the efforts of managers in specific and strategic actions.

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INTRODUCTION AND OBJECTIVE: Chronic use of testosterone replacement therapy (TRT) might impact cardiovascular (CV) risk. Clinical trials for recently approved TRTs have shown impacts on blood pressure (BP) that led to an increase anti-hypertensive dose or new starts: e.g., Xyosted (10% of patients in a 1-year study) and Jatenzo (7.2% in a 4-month study). Here we present the effect of oral testosterone undecanoate (TLANDO, a novel prodrug of bioidentical testosterone) on BP and CV risk including Framingham Risk Score (FRS), and dipping patterns. The objective was to assess the impact of TLADO treatment on BP and CV risk in hypogonadal men.METHODS: Assessment of BP was conducted in a 16-week, multicenter, open-label, single arm ambulatory blood pressure monitoring (ABPM) study in hypogonadal men (N[138). A fixed dose of 225 mg TLANDO was given BID orally for 16 weeks. 24-hr mean changes from baseline (CBL) of BP were measured and analyzed. Subgroup analysis of systolic blood pressure (SBP) CBL was performed in subjects categorized as low, moderate, or high CV FRS risk at baseline (BL). Dipping was also measured. Dipping was categorized as reverse dipper (<0%), non-dipper (0-10%), dipper (10-20%), and extreme dipper (!20%).RESULTS: Demographics were 53.8 AE10.2 yrs, BMI 33.1 AE5.8 kg/m 2 , 79% white ethinicity. Co-morbidities were obesity (30%), type 2 diabetes (24%) and hypertension (48%). 126 subjects completed the study and 118 subjects had valid 24-hr evaluable ABPM data at both baseline and EOS. Overall, T was well tolerated with no death, no drug related SAEs, and no major adverse cardiovascular events (MACE). 1.4% of subjects either had an increase in anti-hypertensive medication dose or started a new medication with T treatment. 24-hr mean (95% CI) SBP CBL was 3.8 AE2.1 mmHg. 25 subjects had SBP>140 mmHg at BL and their 24-hr mean SBP CBL was -3.4 mmHg. Among them, 8 (32%) subjects were normalized post-treatment. Based on FRS categories at BL, 40 (33.9%), 74 (62.7%), and 4 (3.4%) subjects were at low, moderate and high risk, respectively. 24-hr mean SBP CBL for low, moderate, and high-risk subjects was 2.6, 4.8, and -1.8 mmHg, respectively. Post TLANDO treatment, shifts from less dippers at BL to greater dippers at EOS were slightly higher (or comparable with the opposite shifts) implying lower all-cause mortality.CONCLUSIONS: Marginal increases in BP, the dipping shifts, and the FRS with TLANDO treatment does not appear to have a meaningful impact on CV risk.