Use of Seamless Study Designs in Oncology Clinical Development- A Survey Conducted by IDSWG Oncology Sub-team.

Seamless study designs have the potential to accelerate clinical development. The use of innovative seamless designs has been increasing in the oncology area; however, while the concept of seamless designs becomes more popular and accepted, many challenges remain in both the design and conduct of these trials. This may be especially true when seamless designs are used in late phase development supporting regulatory decision-making.

A Systematic Review of Adaptive Seamless Clinical Trials for Late-Phase Oncology Development.

Introduction: Although oncology has seen large scientific and clinical advances over the last decade, it also has one of the lowest success rates for novel agents across therapeutic areas. Adaptive clinical trial design has been a popular option for increasing clinical trial efficiency and the chances of trial success. Seamless clinical trial design are studies in which two or more clinical trial phases are combined into a single study with a pre-specified transition between stages.

Platform trials to evaluate the benefit-risk of COVID-19 therapeutics: Successes, learnings, and recommendations for future pandemics.

Background: In response to the COVID-19 global pandemic, multiple platform trials were initiated to accelerate evidence generation of potential therapeutic interventions. Given a rapidly evolving and dynamic pandemic, platform trials have a key advantage over traditional randomized trials: multiple interventions can be investigated under a master protocol sharing a common infrastructure.

Methods: This paper focuses on nine platform trials that were instrumental in advancing care in COVID-19 in the hospital and community setting.

Clinical trial considerations for pediatric cancer drug development.

Oncology has been one of the most active therapeutic areas in medicinal products development. Despite this fact, few drugs have been approved for use in pediatric cancer patients when compared to the number approved for adults with cancer. This disparity could be attributed to the fact that many oncology drugs have had orphan drug designation and were exempt from Pediatric Research Equity Act (PREA) requirements.

RESTART trial design: two-stage seamless transition design with operational considerations.

Oncology/hematology is a competitive therapeutic area where the landscape is constantly evolving. With regulatory support, many drug developers have spent a lot of resources on the operationalization of innovative clinical trial designs, for example, adaptive Bayesian designs in confirmatory clinical trial settings. While overall survival is considered the gold standard in these designs, it is often not a viable choice in identifying treatment efficacy at a reasonable pace, especially for early-stage therapies.

The win odds: statistical inference and regression.

Generalized pairwise comparisons and win statistics (i.e., win ratio, win odds and net benefit) are advantageous in analyzing and interpreting a composite of multiple outcomes in clinical trials.

Advancing innovative clinical trials to efficiently deliver medicines to patients.

Complex innovative designs in clinical trials have the potential to increase efficiency and lower the cost of drug development, improving patient access to therapies. This article highlights designs and approaches based on a meeting linked to an ongoing FDA pilot program in the field.

Extrapolation as a Default Strategy in Pediatric Drug Development.

Pediatric drug development lags adult development by about 8 years (Mulugeta et al. in Pediatr Clin 64(6):1185-1196, 2017). In such context, many incentives, regulations, and innovative techniques have been proposed to address the disparity for pediatric patients.

Real-World Evidence Utilization in Clinical Development Reflected by US Product Labeling: Statistical Review.

The US Food and Drug Administration (FDA) has shown scientific discretion in interpreting the substantial evidence requirement for the approval of new drugs with its considerations on the use of single controlled or uncontrolled trials (Federal Food, Drug, and Cosmetic Act § 505(d), 21 USC 355(d), 1962). With the passage of the 21st Centuries Cures Act (21st Century Cures-patients. House, Energy and Commerce Committee, Washington, DC, 2019 available at: https://energycommerce.

Bone Mineral Density to Assess Pediatric Bone Health in Drug Development.

Background: Pediatric bone health is an important part of the safety assessment of inhaled corticosteroids and certain other drugs. Current regulatory guidance for assessment of bone health for intranasal and inhaled corticosteroid drugs is a single 1-year study of linear growth.

Objective: The objective of this study was to assess whether a significant change in bone mineral density (BMD) could be observed during a 12-month period in pediatric patients being treated for asthma with an inhaled corticosteroid using a previously conducted study.

Flexible Cure Rate Modeling Under Latent Activation Schemes.

With rapid improvements in medical treatment and health care, many datasets dealing with time to relapse or death now reveal a substantial portion of patients who are cured (i.e., who never experience the event).

Modelling geographically referenced survival data with a cure fraction.

The emergence of geographical information systems and related softwares nowadays enables medical databases to incorporate the geographical information on patients, allowing studies in spatial associations. Public health administrators and researchers are often interested in detecting variation in survival patterns by region or county in order to understand the possible factors that contribute towards such spatial discrepancies. These issues have led statisticians to develop survival models that account for spatial clustering and variation.