Safety Data Collection Research Articles

FOLLOWING THROUGH: How Industry is Continually Improving the Safety of Offshore Development Post-Horizon

Abstract The oil and natural gas industry has worked collaboratively in many areas to make great strides to improve the safety of offshore drilling and producing operations since the Horizon incident in the U.S. Gulf of Mexico. The paper will discuss these activities. Immediately following the incident, the U.S. oil and natural gas industry launched a comprehensive review of offshore safety and operations to identify potential improvements in spill prevention, intervention, and response capabilities. Four joint industry task forces were assembled to focus on the critical areas of equipment, operating procedures, subsea well control and oil spill response. In addition to their own work, the task forces fully considered the recommendations of the Presidential Oil Spill Commission in forming their recommendations to improve offshore safety and response in the respective four areas. One of the major recommendations and actions directly linked to the Presidential Commission recommendations was the formation of an industry organization fully focused on Safety and Environmental Management Systems (SEMS) and managing risk. The industry organization formed is the Center for Offshore Safety (COS). The COS is fully focused on SEMS and its continual improvement through SEMS Auditing, safety data collection and analysis, good practice development, and sharing industry information. Additionally, there has been a continuing special focus on new and enhanced Industry standards. The task force on equipment and other post-Horizon reports contained strong recommendations on the need to develop new and revised standards to enhance safety in the offshore. This work was done through the standards development process and organizations including collaboration with national and international Standards Development Organizations, the offshore oil and gas community, and the Federal government. The presentation will give an overview of the new and revised standards work to date including API Standard 53 Blowout Prevention Equipment Systems for Drilling Operations; API Standard 65-2 Isolating Potential Flow Zones During Well Construction; and API RP 96 Deepwater Well Design and Construction.

Research and application of key technologies for dam safety monitoring based on LoRa

Aiming at the problems of high power consumption, weak scalability and short wireless transmission distance of dam safety monitoring system, the key technology of dam safety monitoring based on Lora is proposed. An intelligent monitoring terminal is designed based on ARM LPC1788 and Lora wireless communication module. The low-power relay mode with Lora and 4G transmission function is adopted, and the active loop calling process and threshold trigger early warning process are designed. The platform software automatically receives data to realize the intelligent collection, analysis and early warning of dam multi factor safety data. The engineering application effect is good.

COVID-19 vaccination in haematology patients: an Australian and New Zealand consensus position statement.

Australia and New Zealand have achieved excellent community control of COVID‐19 infection. In light of the imminent COVID‐19 vaccination roll out in both countries, representatives from the Haematology Society of Australia and New Zealand and infectious diseases specialists have collaborated on this consensus position statement regarding COVID‐19 vaccination in patients with haematological disorders. It is our recommendation that patients with haematological malignancies, and some benign haematological disorders, should have expedited access to high‐efficacy COVID‐19 vaccines, given that these patients are at high risk of morbidity and mortality from COVID‐19 infection. Vaccination should not replace other public health measures in these patients, given that the effectiveness of COVID‐19 vaccination, specifically in patients with haematological malignancies, is not known. Given the limited available data, prospective collection of safety and efficacy data of COVID‐19 vaccination in this patient group is a priority.

Pomalidomide Plus Low-Dose Dexamethasone in Relapsed/Refractory Multiple Myeloma Patients: Results of the Real-World "POWERFUL" Study.

The “POWERFUL” multicenter, retrospective, and prospective study investigated the effectiveness of pomalidomide plus low-dose dexamethasone (POM/LoDex) therapy in relapsed/refractory multiple myeloma in routine care in Greece. Ninety-nine eligible adult patients treated with POM/LoDex according to the approved label after having received ≥2 prior therapies, including lenalidomide and bortezomib, were consecutively enrolled between 16 November 2017 and 21 February 2019 in 18 hematology departments. Fifty patients (50.5%) started POM/LoDex as third-line treatment. During the treatment period (median: 8.3 months; range: 0.3–47.6 months), the median POM dose was 4 mg/day, and 31.3% of the patients received additional antimyeloma agents. The overall response rate was 32.3%. During a median follow-up period of 13.8 months (Kaplan–Meier estimate), the median progression-free survival (PFS) was 10.5 months (95% CI: 7.4–14.4). The PFS was not significantly different between patients receiving POM/LoDex in the third versus later line of therapy, nor between patients receiving concomitant antimyeloma therapy versus POM/LoDEx doublet. During the prospective safety data collection period (median: 7.6 months) among patients with prospective follow-up (N = 75), POM-related adverse event incidence rate was 42.7% (serious: 18.7%; grade ≥ 3 hematological POM-related adverse events: 8.0%). Only neutropenia (13.3%) was reported at a frequency ≥10%. In conclusion, in this real-world study, POM/LoDex displayed a long PFS with no new safety signals emerging.

Measuring safety in older adult care homes: a scoping review of the international literature

BackgroundSafety is a key concern in older adult care homes. However, it is a less developed concept in older adult care homes than in healthcare settings. As part of study...

The need for a global COVID-19 maternal immunisation research plan

The need for a global COVID-19 maternal immunisation research plan

The art of prevention: COVID-19 vaccine preparedness for the dermatologist.

As COVID-19 vaccinations begin, dermatologists must be aware of the cutaneous adverse events reported in the clinical trials, including injection site and hypersensitivity reactions, and emerging evidence of dermal filler injection reactions after vaccination. The filler reaction may represent the development of a delayed-type hypersensitivity in the setting of another immunologic trigger (i.e., the vaccine). After conducting a literature review of similar reactions, their pathophysiology, and management, we present a set of timely clinical considerations for counseling, prevention, and management of possible cutaneous sequelae of the COVID-19 vaccine. We encourage documentation of vaccine-related reactions to aid the safety data collection in the Vaccine Adverse Event Reporting System and the American Academy of Dermatology COVID-19 Registry.

Effectiveness of drug postmarketing all-case surveillance as a safety measure in Japan.

Introduction:The drug pharmacovigilance system in Japan is similar to those in the European Union (EU) and the United States. As a unique Japanese pharmacovigilance program, postmarketing all-case surveillance (PMACS) is required. PMACS plays a key role for postmarketing activities, but there are challenges that place much burden on PMACS conduct. This study investigates the impact of PMACS on postmarketing activities in Japan and proposes its potential improvement. This study also seeks the possibility to expand PMACS beyond Japan.Materials and Methods:Reexamination reports issued from 2017 to 2019 were identified in September 2020 by searching ‘reexamination report’ and ‘201701’ to ‘201912’ on the Pharmaceuticals and Medical Devices Agency website. The corresponding Package Insert (PI) change orders and premarketing review reports were also identified. Reviewing these regulatory documents allowed for investigation of the PMACS impact on postmarketing activities.Results:More than half (57%) of the drugs with PMACS had ‘Limited dosing experience in Japan’ as a reason for the PMACS requirement. As a safety measure, no PI change orders were imposed on 33% and 28% of drugs with and without PMACS, respectively. The means of the number of PI change orders were 2.23 and 2.14 for drugs with and without PMACS, respectively. There were no reexamination reports mentioning any concerns related to efficacy.Discussion and Conclusion:PMACS should not be imposed only because of limited dosing experience in Japan at the premarketing stage. Rather, PMACS should focus on (1) collection of safety data (not efficacy), (2) necessity of distribution control, and/or (3) collection of case details for drugs with a limited treated population. PMACS also has the potential to be utilized in the EU and the United States, as their regulatory frameworks are acceptable for PMACS. Naglazyme (galsulfase) is a case where the PMACS-like studies have been required in each region.Plain Language SummaryEffectiveness of data collection for all patients who receive a new drug as a safety measure in JapanIntroduction:In Japan, a drug company is obligated to conduct data collection after a new drug launch as an approval condition. The obligation is a unique Japanese requirement where a company must collect data from all patients receiving the drug in Japan in cooperation with hospitals. This is expected to contribute to intensive data collection and better drug distribution control and could potentially be useful in countries beyond Japan. However, no clear criteria have been established for decision making, despite the significant burden for companies and hospitals. Therefore, this study aimed to investigate the impact of the obligation on safety measures and efficacy data collection and propose a potentially improved drug scope to impose the obligation.Materials and Methods:Reexamination of reports issued by the Pharmaceuticals and Medical Devices Agency between 2017–2019.Results:More than half (57%) of the included drugs had ‘Limited dosing experience in Japan’ as a reason for the obligation being required. However, regulatory order to change drug label, an action based on safety signal identification, was imposed on 33% and 28% of drugs with and without the obligation, respectively. The means of the number of the label change orders were 2.23 and 2.14 for drugs with and without obligation, respectively. Meanwhile, some drugs were highlighted as potential factors for better application of the obligation.Conclusion:According to these results, the obligation should be imposed on a limited number of drugs by focusing not on dosing experience in Japan but on safety (not efficacy) data collection, necessity of distribution control, and/or collection of case details for drugs with a limited treated population. The obligation also has the potential to be utilized in the EU and the United States, as their regulatory frameworks are acceptable for the obligation.

Safety first: Tracking adverse events associated with new therapies for people with hemophilia

Safety first: Tracking adverse events associated with new therapies for people with hemophilia

Analysis of environmental risks and accidents at work in urban solid waste collection services

abstract: The heterogeneity and the volume of solid urban waste generated daily cause difficulties in their management, which causes environmental impacts, health and public safety problems. Among all waste management activities, collection is one of the most relevant from an occupational point of view because employees are subject to physical, chemical, biological, ergonomic risks as well as suffering accident. This article aims to instruct companies to apply multidisciplinary management tools that conciliate and serve as a basis for decision making related to environmental and occupational safety management. Therefore, the Ad Hoc Environmental Impact Assessment techniques and the RMT Risk Management Tool were used to identify the environmental impacts generated and the risks to which employees in the urban solid waste collection sector are exposed. It happened through the collection of operational, environmental information and work safety data, in 2017, of companies operating in 7 (seven) municipalities in the state of Rio Grande do Sul. The Ad Hoc report showed that the environmental aspects of surface water, groundwater, soil, odor and air pollution, generate negative and irreversible environmental impacts. Furthermore, the analysis of accidents at work, the identification of the major agents that cause accidents at work and the nature of injuries, showed their high frequency and severity. In total 60 accidents were recorded and all occurred with garbage collectors. Among these, 13 had as causative agents “glassware, fiberglass, blade, except vial, bottle” and the most recurrent types of injuries were “excoriation and abrasion (superficial wound)” and “by cutting, laceration, blunt wound, puncture (open wound)”, both with 22% of occurrence, which generate work leave. Furthermore, the elaboration of Action Plans and application of the 5W2H Quality Management tool proved to be excellent tools for assessments regarding the minimization of environmental impacts and the control of accidents at work.

Hazards identification and risk analysis in surface mines of Pakistan using fault tree analysis technique

Purpose. Technology has advanced significantly but still mining industry faces a higher number of accidents. The purpose of the research is to identify the common hazards and associated risk which are the root causes of accidents in surface mines of Pakistan and to suggest the preventive measures to enhance safety at workplace. Methods. Integrated approach used in this research work involves: collection of mine accidents data from related Government departments; occupational safety data collection from mine sites with questionnaire; fault tree analysis method applied based on three groups of factors/causes obtained from 3E’s Model i.e. Engineering, Education and Enforcement that causes accidents in mine; risk assessment and suggestion of preventive measures. Findings. In this study forty three root causes of accidents in surface mines are identified and presented as basic events and undeveloped events in the Fault Trees. A compressed picture of the root causes is revealed leading to accidents in mine. The main causes identified are human errors, unsafe operating procedure, lack of machinery, lack of personal protective equipment, environmental and haulage related hazards and violation of law. Originality.The root causes of accidents in surface mines have been identified. For the first time, the visual paths to accidents causation in surface mines of Pakistan are outlined through fault tree analysis technique. Practical implications. The identified causes of accidents along with the suggested preventive measures can be used to avoid/curtail the number and severity of accidents in surface mines and can save lives of workers and economy. Keywords: hazards identification, surface mine, accidents, fault tree analysis, risk assessment, preventive measures

Enhanced post-licensure safety surveillance of a new recombinant acellular pertussis vaccine licensed as a monovalent (aP, Pertagen®) and tetanus, reduced-dose diphtheria combination (TdaP, Boostagen®) vaccine for immunization of adolescents and adults in Thailand

A new generation of recombinant acellular pertussis vaccine containing genetically inactivated pertussis toxin (PTgen) was licensed as a monovalent pertussis vaccine (aPgen; Pertagen®) and in combination with tetanus and reduced-dose diphtheria (TdaPgen; Boostagen®) for active immunization in individuals aged 11 years and older in Thailand in 2016. We here report post-marketing safety data on the use of the vaccines in individuals in the community obtained through active pharmacovigilance surveillance including pregnant women participating in a prospective observational study.Between May 2017 and February 2020 for TdaPgen and between June 2018 and February 2020 for aPgen, participating health care providers vaccinated and collected safety data for 11,429 exposed adolescents and adults. This included 1778 pregnant women. The incidence rate of adverse events following immunization (AEFIs) was 11.5 per 1000 of vaccinated individuals (95% confidence interval (95% CI) 9.7–13.6). AEFIs mostly concerned local pain at the injection site and muscle pain, and symptoms were mild and mostly resolved within a few days with no complications. The incidence rate of AEFIs in women vaccinated during pregnancy was 1.1 per 1000 (95% CI 0.3–4.1). Of 833 pregnant women vaccinated with recombinant aPgen or TdaPgen, 91.4% (95% CI 89.3–93.3) had uncomplicated pregnancies and 98.7% (95% CI 97.7–99.4) of the 855 babies delivered by these women were born healthy, which exceeds rates generally reported in Thailand. There were no vaccine-related serious adverse events reported during the surveillance period. In conclusion, active pharmacovigilance confirms that the recombinant pertussis vaccines aPgen (Pertagen) and TdaPgen (Boostagen) are safe in adolescents and adults, including pregnant women vaccinated in the second or third trimester of pregnancy.

Pomalidomide Plus Low Dose Dexamethasone in Relapsed/Refractory Multiple Myeloma Patients: Results of the Real-World ‘Powerful’ Study

Pomalidomide Plus Low Dose Dexamethasone in Relapsed/Refractory Multiple Myeloma Patients: Results of the Real-World ‘Powerful’ Study

Ten-year safety follow-up and post-explant analysis of an anterior chamber phakic IOL.

To assess endothelial cell loss (ECL) rate and collect safety data in patients with AcrySof L-series Cachet phakic intraocular lens (pIOL) up to 10 years post-implantation. Clinical settings in the United States, European Union, and Canada. Nonrandomized, observational, open-label safety study. Central and peripheral endothelial cell density was evaluated and compared with 6-month post-implantation baseline. Nonlinear analysis was performed to identify factors affecting post-explantation ECL. Additional evaluations included uncorrected visual acuity (UCVA), corrected distance visual acuity (CDVA), adverse device effects (ADEs), and serious adverse events (SAEs). The study included 1123 implanted eyes (mean age, 37.5 years). At 10 years, mean central and peripheral ECL was 16% (1.7% annualized). Explantations were performed in 10% of eyes (n = 136/1323). For eyes with pIOL explantation because of ECL (7%), annualized ECL rate post-explantation was numerically lower compared with the overall rate in eyes that underwent explantation for any reason (annualized rate, -1.65% vs -2.03%, respectively; n = 96) and compared with pre-explantation ECL. Mean ± SD CDVA and UCVA were -0.12 ± 0.11 and 0.03 ± 0.22 logarithm of the minimum angle of resolution, respectively. Common ocular ADEs included ECL (10%), pIOL extraction (9%), iris adhesion (7%), and pupillary deformity (2%). Common SAEs included pIOL extraction (11%), ECL (9%), and iris adhesions (8%). Cachet pIOLs were associated with long-term ECL in some cases. Overall, only 10% of all implanted eyes underwent explantation during 10-year follow-up. In patients requiring explantation because of ECL, the annualized ECL rates decreased post-explantation in some eyes. Continued monitoring of patients regardless of explantation is recommended.

Guidance for vaccine safety data collection, presentation and analysis (SO1-D2.7)

Guidance for vaccine safety data collection, presentation and analysis (SO1-D2.7)

Safety, immunogenicity, and efficacy of a Clostridioides difficile toxoid vaccine candidate: a phase 3 multicentre, observer-blind, randomised, controlled trial

In the absence of a licensed vaccine, Clostridioides (formerly Clostridium) difficile infection represents a substantial health burden. The aim of this study was to evaluate the efficacy, immunogenicity, and safety of a toxoid vaccine candidate. We did a phase 3 multicentre, observer-blind, randomised, controlled trial at 326 hospitals, clinics, and clinical research centres in 27 countries in the USA, Canada, Latin America, Europe, and the Asia-Pacific region. We included adults aged 50 years or older who were considered to be at an increased risk of C difficile infection because they had previously had two hospital stays (each ≥24 h in duration) and had received systemic antibiotics in the previous 12 months (risk stratum 1), or because they were anticipating being admitted to hospital for 72 h or more for elective surgery within 60 days of enrolment (risk stratum 2). Eligible participants were stratified by geographical region and the two risk strata, and randomly assigned (2:1), with a fixed block size of three, to receive either a C difficile toxoid vaccine candidate, containing toxoids A and B (C difficile vaccine candidate group), or a placebo vaccine (placebo group). Participants, investigators, and personnel responsible for collecting safety data and analysing blood and stool samples were masked to group assignment. Personnel responsible for study product preparation and administration were not masked to group assignment. One dose (0·5 mL) of C difficile vaccine candidate or placebo vaccine was administered intramuscularly on days 0, 7, and 30. The primary outcome was the efficacy of the vaccine in preventing symptomatic C difficile infection, defined as having three or more loose stools in a period of 24 h or less, loose stools for 24 h or more, and a PCR-positive test for C difficile toxin B in a loose stool sample, within 3 years after the final vaccine dose. The primary outcome was measured in the modified intention-to-treat population (ie, all participants who received at least one injection of the assigned vaccine). The safety of the vaccine was assessed in the safety analysis set (ie, all participants who had received at least one injection, analysed according to the product received). This study is registered with WHO/ICTRP, number U111-1127-7162, and ClinicalTrials.gov, number NCT01887912, and has been terminated. Between July 30, 2013, and Nov 17, 2017, we enrolled and randomly assigned 9302 participants to the C difficile vaccine candidate group (n=6201) or to the placebo group (n=3101). 6173 (99·5%) participants in the C difficile vaccine candidate group and 3085 (99·5%) participants in the placebo group received at least one dose of the vaccine. The study was terminated after the first planned interim analysis because of futility. In the C difficile vaccine candidate group, 34 C difficile infections were reported over 11 697·2 person-years at risk (0·29 infections per 100 person-years [95% CI 0·20-0·41]) compared with 16 C difficile infections over 5789·4 person-years at risk in the placebo group (0·28 infections per 100 person-years [0·16-0·45]), indicating a vaccine efficacy of -5·2% (95% CI -104·1 to 43·5). In the C difficile vaccine candidate group, 2847 (46·6%) of 6113 participants reported an adverse event within 30 days of injection compared with 1282 (41·9%) of 3057 participants in the placebo group. The proportion of participants who had an adverse event leading to study discontinuation was 4·8% in both groups (296 participants in the C difficile vaccine candidate group and 146 participants in the placebo group). 1662 (27·2%) participants in the C difficile vaccine candidate group reported at least one serious adverse event compared with 851 (27·8%) participants in the placebo group. In adults at risk for C difficile infection, a bivalent C difficile toxoid vaccine did not prevent C difficile infection. Since the C difficile vaccine candidate met the criteria for futility, the study was terminated and clinical development of this vaccine candidate was stopped. Sanofi Pasteur.

Road safety data collection systems in Iran: A comparison based on relevant organizations

PurposeVarious organizations and institutions are involved in road traffic injury (RTI) and crash registration such as police, forensic medicine organization, hospitals and emergency medical services. But there is a substantial uncertainty in interpreting the data, duplicated data collection and missing data in relation to RTI in most systems. This study aims to identify data sources for RTI surveillance in Iran and to explore traffic safety data source domains, data elements and detailed information by each data source. MethodsThis is a qualitative study which was conducted in 2017 in Iran. Data were collected employing semi-structured interviews with informants in road safety organizations in relation to traffic safety including Police, Ministry of Health and Medical Education as well as Forensic Medicine Organization and other authorities-in-charge. For completing the preliminary extraction information, the minimum data set was used and compared in each system. ResultsEight different organizations relevant to road traffic safety were identified. The main domain of data provided by each one consists of Emergency Medical System form, Police KAM114 form, Ministry of Transport and Road Administration, Red Crescent Organization/Disaster Management Information System, Ministry of Health and Medical Education, Forensic Medicine Organization, Insurance Company and Ministry of Justice. Each system has its own database, based upon its scope and mainly at crash and post-crash status and little on pre-crash circumstance. ConclusionAll current registry systems are not surveillance systems for RTI prevention. Huge data have been collected in various registry systems in Iran, but most of the collected variables are duplicated in each system. On the other hand, some variables like alcohol and substance abuse, child seat belt, helmet use in relation to RTI prevention are missed in all systems. Accordingly, it is a critical need to integrate and establish a comprehensive surveillance system, with focus on the goal of each system and collection of minimum data in each organization, which currently is underway.

Spatial-Cluster Signal Detection in Medical Devices Using Likelihood Ratio Test Method.

With more and more medical device databases being developed, there is an increasing interest in learning the geographical patterns of medical-device-related adverse events (AEs). For a specific medical device and an adverse event (AE) of interest, our aim is to detect a spatial-cluster signal that has a significantly higher AE rate than the AE rates for other regions, when the exposure information is available. We develop a likelihood ratio test (LRT) method incorporating exposure information, by geographical region, for spatial-cluster signal detection when the underlying observed health outcome associated with the medical device of interest is a Poisson-modeled count data (e.g., an outcome of AE count). An extensive simulation study shows that this method has good power, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). The application of the method is demonstrated by two hypothetical case studies regarding a medical device that is used for patients who have reached end-stageheartfailure. A methodological framework for exploring geographic patterns in device safety surveillance is discussed, including safety data collection, statistical tools, and display of the analysis results. The proposed statistical method can be used for spatial-cluster signal detection for an AE of interest from medical device registries or other databases that have patient-level geographical information.

Patient feedback for safety improvement in primary care: results from a feasibility study.

ObjectivesPatient involvement in safety improvement is a developing area of research. The aim of this study was to investigate the feasibility of a patient feedback on safety intervention in primary care. Specifically, the intervention acceptability, fidelity, implementation enablers and barriers, scalability, and process of systematically collecting safety data were examined.Design, setting and participantsMixed-methods feasibility trial with six purposively selected Australian primary care practices.InterventionThe intervention comprised an iterative process with a cycle of measurement, learning, feedback, action planning and implementation period of 6 months.Primary and secondary outcomesQualitative and quantitative data relating to feasibility measures (acceptability, fidelity, enablers, barriers, scalability and process of collecting safety data) were collected and analysed.ResultsA total of n=1750 patients provided feedback on safety. There was a statistically significant increase in mean patient safety scores indicating improved safety (4.30–4.37, p=0.002). Staff deemed the intervention acceptable, with minor recommendations for improvement. Intervention fidelity was high and implementation enablers were attributed to the intervention structure and framework, use of intuitive problem-solving approaches, and multidisciplinary team involvement. Practice-based safety interventions resulted in sustainable and measurable changes to systems for safety, such as increased access to care and improved patient information accuracy.ConclusionsThe findings indicate that this innovative patient feedback on safety intervention is feasible for scale-up to a larger effectiveness trial and further spread into policy and practice. This intervention complements existing safety improvement strategies and activities, and integrates into current patient feedback service requirements for Australian primary care. Further research is needed to examine the intervention effects on safety incident reduction.

A phase Ib/III randomized, double-blind, placebo-controlled study of tazemetostat plus doxorubicin as frontline therapy for patients with advanced epithelioid sarcoma.

TPS11573 Background: Epithelioid sarcoma (ES) is characterized by loss of inhibitor of integrase 1 (INI1), allowing enhancer of zeste homologue 2 (EZH2) to repress cell differentiation and promote tumorigenesis. Tazemetostat (TAZ) is an EZH2 inhibitor approved by the FDA as monotherapy for the treatment of patients (pts) aged ≥16 years with metastatic or locally advanced ES ineligible for complete resection. The most common ( > 20%) adverse events include pain, fatigue, nausea, decreased appetite, vomiting, and constipation. TAZ demonstrated anti-cancer activity in ES pts who previously received doxorubicin (dox), a commonly used front line FDA approved therapy for soft tissue sarcomas (STS), including ES. Preclinical studies have demonstrated synergy between TAZ and dox. This phase 1b/3 study (NCT04204941) is assessing the safety and efficacy of TAZ + dox in pts with advanced ES. Methods: This study is enrolling treatment-naïve adult pts with histologically confirmed STS (phase 1b) or INI1-deficient ES pts (phase 3) with ECOG performance status of 0-2 and life expectancy of ≥3 months. The open-label phase 1b portion is currently enrolling up to 24 patients with STS. The primary objectives are to evaluate the safety and tolerability of TAZ + dox, and to identify the recommended phase 3 dose (RP3D). Using a standard 3 + 3 design, TAZ will be evaluated at 3 dose levels (400 mg, 600 mg, and 800 mg orally BID) with standard fixed dose of dox (75 mg/m2 on day 1 of 21-day cycles for up to 6 cycles). After completion of dox, pts will continue to receive TAZ monotherapy until disease progression or intolerable toxicity. Up to 12 additional pts will be enrolled at the maximum tolerated dose for collection of additional safety and pharmacokinetic (PK) data. The double-blind phase 3 study will randomize (1:1) up to 140 pts to receive either TAZ (RP3D) + dox (75 mg/m2) or placebo + dox. The adaptive study design will allow sample size re-estimation (at interim analysis) to up to 200 pts. Pts may continue TAZ or placebo monotherapy after completing 6 cycles of TAZ + dox. Tumor assessments will be performed at screening and every 6 weeks from the start of dosing. The primary objective of phase 3 will be to evaluate the progression-free survival (PFS) by independent review committee. Secondary objectives will include assessment of PFS by investigators, overall survival, safety, disease control rate, overall response rate, duration of response, time to subsequent anticancer therapy, PFS on next treatment, quality of life, and PK. Clinical trial information: NCT04204941 .