Related Experiment Video

Updated: Jun 6, 2026

Chimeric Antigen Receptor T Cell Manufacturing on an Automated Cell Processor
06:18

Chimeric Antigen Receptor T Cell Manufacturing on an Automated Cell Processor

Published on: August 18, 2023

Pivotal trial design considerations for new and next generation cell and gene therapies

Patricia Anderson1, Zhenzhen Xu2, Evgeny Degtyarev3

  • 1Biostatistics Consulting Services, ICON Plc, Raleigh, NC, USA.

Journal of Biopharmaceutical Statistics
|June 5, 2026
PubMed

Insights

Developing new cell and gene therapies (CGTs) presents challenges, especially when comparing them to existing standards of care. This article explores innovative trial designs, like hybrid studies, to evaluate novel CGTs effectively.

Area of Science:

  • Biotechnology and Pharmaceutical Sciences
  • Clinical Trial Design
  • Regenerative Medicine

Background:

  • Cell and gene therapies (CGTs) have advanced significantly, with over 30 FDA-approved products as of August 2024.
  • Current CGTs show promise but face limitations including manufacturing delays and variable response durability.
  • Emerging CGTs aim to improve efficacy or overcome existing therapy drawbacks.

Purpose of the Study:

  • To address the unique challenges in developing new CGTs when approved therapies are the standard of care (SOC).
  • To explore the feasibility of head-to-head comparisons between novel and existing CGT products.
  • To discuss potential study designs for evaluating new CGT effectiveness, including hybrid approaches.

Main Methods:

  • Analysis of challenges in conventional randomized controlled trials (RCTs) and single-arm trials for new CGT development.
  • Discussion of alternative pivotal trial strategies, focusing on hybrid study designs.
  • Review of regulatory and clinical considerations for comparing CGTs.

Main Results:

  • Conventional trial designs may be insufficient for evaluating new CGTs against established SOC CGTs.
  • Hybrid study designs offer a potential strategy to overcome limitations of traditional trial frameworks.
  • The need for innovative trial methodologies is highlighted to facilitate the development of next-generation CGTs.

Conclusions:

  • Developing new CGTs requires careful consideration of trial design, especially when comparing against approved therapies.
  • Hybrid study designs present a promising avenue for assessing the efficacy and safety of novel CGTs.
  • Continued dialogue among stakeholders is essential to advance the field and optimize clinical trial strategies for CGTs.
Keywords:
CAR T-cellPivotal study designcell and gene therapycell therapycell-based gene therapygene therapy

More Related Videos

A Real-time Potency Assay for Chimeric Antigen Receptor T Cells Targeting Solid and Hematological Cancer Cells08:46

A Real-time Potency Assay for Chimeric Antigen Receptor T Cells Targeting Solid and Hematological Cancer Cells

Published on: November 12, 2019

Preparation and Gene Modification of Nonhuman Primate Hematopoietic Stem and Progenitor Cells11:16

Preparation and Gene Modification of Nonhuman Primate Hematopoietic Stem and Progenitor Cells

Published on: February 15, 2019

Related Concept Videos

Gene Therapy00:59

Gene Therapy

Gene therapy is a technique where a gene is inserted into a person’s cells to prevent or treat a serious disease. The added gene may be a healthy version of the gene that is mutated in the patient, or it could be a different gene that inactivates or compensates for the patient’s disease-causing gene. For example, in patients with severe combined immunodeficiency (SCID) due to a mutation in the gene for the enzyme adenosine deaminase, a functioning version of the gene can be inserted. The...
Gene Therapy00:59

Gene Therapy

Gene therapy is a technique where a gene is inserted into a person’s cells to prevent or treat a serious disease. The added gene may be a healthy version of the gene that is mutated in the patient, or it could be a different gene that inactivates or compensates for the patient’s disease-causing gene. For example, in patients with severe combined immunodeficiency (SCID) due to a mutation in the gene for the enzyme adenosine deaminase, a functioning version of the gene can be inserted. The...
Types of Biopharmaceutical Studies: Controlled and Non-Controlled Approaches01:23

Types of Biopharmaceutical Studies: Controlled and Non-Controlled Approaches

Biopharmaceutical studies constitute a vital field aiming to enhance drug delivery methods and refine therapeutic approaches, drawing upon diverse interdisciplinary knowledge. In research methodologies, the choice between controlled and non-controlled studies significantly influences the study's reliability and accuracy.
Non-controlled studies, commonly employed for initial exploration, lack a control group, rendering them susceptible to biases and external influences. In contrast, controlled...
Preclinical Development: Overview01:28

Preclinical Development: Overview

Preclinical development consists of a series of tests that ensure the safety and efficacy of a new therapeutic compound before it is tested in humans. There are four main phases to this process. First, safety pharmacology tests are conducted to ensure the drug does not produce any acutely harmful effects. These tests examine parameters such as bronchoconstriction, cardiac dysrhythmias, blood pressure changes, and ataxia. Next, preliminary toxicological testing is performed to determine the...
Biopharmaceutical Factors Influencing Drug Product Design: Overview01:22

Biopharmaceutical Factors Influencing Drug Product Design: Overview

Rational drug product design integrates knowledge of the drug’s physicochemical properties, formulation components, manufacturing techniques, and intended route of administration. Each factor influences the drug’s performance, including how it is released, absorbed, and eliminated in the body.The physicochemical properties of a drug—such as solubility, stability, and particle size—affect its compatibility with excipients and the choice of dosage form. Excipients, though pharmacologically...
Clinical Trials: Overview01:11

Clinical Trials: Overview

Clinical development focuses on how the drug will interact with the human body and encompasses four key phases of clinical trials, each serving a specific purpose in assessing the safety and effectiveness of new drugs. These phases overlap and build upon one another. Phase I involves a small group of healthy volunteers (typically 20-80 individuals) or, in cases where significant toxicity is expected, patients with the targeted disease, such as cancer or AIDS. The volunteers are tested for...