Secondary Endpoints Clause Samples

Secondary Endpoints. Safety and tolerability will be assessed by monitoring AEs, performing physical examinations and clinical laboratory evaluations, measuring vital signs, and recording ECGs.

Secondary Endpoints. ‌ 1) Pathological and histologicalevaluation of the acute thermal effect, produced by the ANET device, on targeted pulmonary nodule/tumor and surrounding tissue to determine if the observed zone of ablation is localized and consistent with the predicted zone of ablation. 2) Characterize any effects on surrounding tissue outside the zone of predicted ablation.

Secondary Endpoints. IRRC-assessed ▇▇▇ and PFS, and OS, in any-risk subjects with previously untreated RCC. Incidence of AEs in all treated subjects with previously untreated advanced or metastatic RCC Exploratory Endpoints: Overall safety and tolerability of NIVO+IPI versus sunitinib. IRRC-assessed ▇▇▇ and PFS, and OS in favourable-risk subjects with previously untreated advanced or metastatic RCC. Explore potential predictive biomarkers of clinical response by analyzing tumor specimens and blood samples for proteins and genes involved in regulating immune responses. Evaluate HRQoL as assessed by FACT-G. Assess disease related symptoms in each arm based on NCCN FKSI-19. Assess changes in global health status based on EuroQol’s EQ-5D.

Secondary Endpoints. Structural changes of PED on OCT-Angiography Mean change in visual acuity at weeks 12, 24 and 52 compared to the baseline. Proportion of patients who gain 5, 10 and 15 letters at weeks 12, 24 and 52 Mean change in central foveal thickness and volume measured by SD-OCT at weeks 12, 24 and 52 compared to the baseline. Mean change in PED height at weeks 24 and 52 compared to the baseline. Proportion of patients with resolution of PED at weeks 24 and 52. Mean number of injections over 52 weeks. Proportion of patients with development of macular atrophy at week 52. The change of retinal function measured by Macular Integrity Assessment (MAIA) at weeks 24 and 52 compared to the baseline. Mean change in National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) score between baseline and weeks 24 and 52.

Secondary Endpoints. ● Objective response rate (O▇▇) as defined by RECIST v1.1 (Appendix B) Patients who respond to treatment and die without PD (including death from study disease), duration of response will be censored at the date of the last objective progression-free disease assessment. For responding patients not known to have died as of the data cut-off date and who do not have PD, duration of response will be censored at the last progression-free assessment date. For responding patients who receive subsequent anticancer therapy (after discontinuation from all study treatment excluding PCI) prior to disease progression, duration of response will be censored at the date of last progression-free assessment prior to the initiation of post discontinuation anticancer therapy ● Duration of overall response as defined by RECIST v1.1 (Appendix B) ● Safety and Adverse events by assessed by CTCAE version 5.0 ● Progression-free survival (PFS) as defined by RECIST v1.1 (Appendix B) ● Overall survival, which is defined as the time from the date of study enrollment to the date of death from any cause. For patients who are still alive as of the data cutoff date, OS time will be censored on the date of the patient’s last contact (last contact for patients in post discontinuation is last known alive date in mortality status).

Secondary Endpoints. PHARMACOKINETIC ENDPOINTS i. For TID dosing, samples will be obtained before Dose 7 and 0.5, 1, 2, 4, and 6 hours after Dose 7. This serial PK sampling may be done for Dose 7, 8, or 9, based on site/patient convenience ii. For BID dosing, samples will be obtained before Dose 5 and 0.5, 1, 2, 4, 6, and 8 hours after Dose 5. This serial PK sampling may be done for Dose 5, 6, or 7, based on site/patient convenience For blood samples (both TID and BID dosing), a ±10-minute window for time points ≤4 hours; ±15 minute for time points between 4 and 24 hours o At any early study discontinuation visits. The timing of these PK samples relative to the last 2 (most recent) doses will be recorded • Noncompartmental analysis will be performed for the following plasma PK parameters, when applicable and if data permit. Other PK parameters may also be calculated. PK parameters, where applicable, will be calculated based on actual times: o AUClast (area under the plasma concentration versus time curve from time 0 to the last quantifiable concentration) o AUCtau (area under the plasma concentration versus time curve over the dosing interval) o AUCinf (area under the plasma concentration versus time curve from time 0 to extrapolated to infinity) o Cmax o Tmax o t1/2z (apparent terminal elimination half-life) o CL/F for AT-281 only (apparent oral clearance) o Vz/F for AT-281 only (apparent volume of distribution)

Secondary Endpoints. 9.2.2.1 Time from randomization to treatment failure defined as virologic failure (see Section 9.2.1), death, or permanent discontinuation of the NNRTI or PI components of the randomized treatment, whichever occurs first. Changes in the NRTI drugs will not constitute treatment failure. Drug-resistant plasma virus as determined at virologic failure by bulk sequencing.

Secondary Endpoints. Length of stay o Aim: Decrease length of hospital stay o Measured: Time (Hours) • Length of time for initial image processing o Aim: Decrease disturbance to surgeon workflow o Measured: Time (Minutes) • Length of time to place all screws o Aim: Reduce the time for screw placement o Measured: Time (Minutes) • Length of time to confirm screw placement o Aim: Reduce the time needed for confirmation of screw location o Measured: Time (Minutes) • Length of time to register images o Aim: To reduce time for registration of reference images o Measured: Time (Seconds) • Estimated Blood Loss (EBL) o Aim: To reduce the EBL of each case o Measured: Milliliters (mL) • Incidence of Malalignment o Aim: To decrease the incidence of pedicle screw malalignment o Measured: Misalignment angle between pilot hole and screw trajectory (degrees) • Complications: Neurological Deficits, Dural Tears, deep wound infections, etc o Aim: To decrease the incidence of intraoperative complications o Measured: number of reported complications while hospitalized • Measurement of 2D fluoroscopy radiation exposure o Aim: to reduce patient and surgeon exposure to radiation o Measured: Exposure measured by Dose Area Product (DAP)

Secondary Endpoints. To cross-validate the prediction models in order to assess the accuracy of their performance in clinical practice and to test their generalizability. This will take place through bootstrapping methods and, mainly, through data splitting. Specifically, through sophisticated sampling methods, the dataset will be split into two: one part of the dataset will be used so as to develop and train the model; the other part will be used to validate it. Proposed prediction models are detailed below. • To identify processes and interactions that can more accurately predict final (i.e., at 18 months) and intermediate (i.e., at 3, 6, 9, 12 and 15 months) psychological outcomes. • To develop a multi-dimensional index of resilience as a function of the biomedical status (BMS), the psychosocial status (PSS) and the functional status (FUS) of the patient. • To deliver an advanced, empirically validated and more inclusive definition of resilience. • To perform a series of moderation, multiple mediation and moderated mediation analyses (e.g., from personality traits to health outcomes, through health-related beliefs and behaviour, with socio-demographic variables as moderating conditions) in order to gain an enhanced understanding of the dynamic process of adaptation to breast cancer, and resilience-as-a-process. • To conduct cost-benefit analysis in order to assess the strengths and limitations of the project outcomes and also determine the best approach to achieve the maximum benefits. • To examine potential differences in the predictive and outcome variables across the four clinical sites of the BOUNCE Pilot Study considering also health care infrastructures and patient flow/support/culture.