Related Experiment Video

Updated: May 1, 2026

Positron Emission Tomography-based Dose Painting Radiation Therapy in a Glioblastoma Rat Model using the Small Animal Radiation Research Platform
07:57

Positron Emission Tomography-based Dose Painting Radiation Therapy in a Glioblastoma Rat Model using the Small Animal Radiation Research Platform

Published on: March 24, 2022

2.2K

PRO-ADD: Patient-empowered dose-finding trials integrating safety, preliminary efficacy and patient-reported outcomes

Emily Alger1, Sumithra J Mandrekar2, Jun Yin3

  • 1Clinical Trial and Statistics Unit, Institute of Cancer Research, UK.

Statistical Methods in Medical Research
|April 30, 2026
PubMed

Insights

Novel oncology drugs require new trial designs. Patient-Reported Outcomes Aided Dose-optimisation Design (PRO-ADD) identifies optimal doses by balancing efficacy and tolerability, improving patient-centric cancer drug development.

Area of Science:

  • Oncology
  • Clinical Trial Design
  • Pharmacometrics

Background:

  • Novel cancer therapies challenge traditional dose-finding assumptions in oncology trials.
  • Existing methods focus on Maximum Tolerated Dose (MTD), which may not be optimal for new treatments.
  • Patient-Reported Outcomes (PROs) are crucial for assessing tolerability with novel immunotherapies and targeted therapies.

Purpose of the Study:

  • To introduce PRO-ADD (Patient-Reported Outcomes Aided Dose-optimisation Design), a novel framework for dose-optimisation in oncology trials.
  • To shift the focus from MTD identification to finding optimal, patient-centric doses.
  • To integrate clinician-assessed dose-limiting toxicities (DLTs), PROs, and preliminary efficacy into dose-finding.

Main Methods:

  • Development of the modular PRO-ADD framework for dose-optimisation.
  • Leveraging PRO-ADD to optimise dosage based on DLTs, PROs, and efficacy.
  • Evaluating PRO-ADD's performance in identifying the optimal dose.

Main Results:

  • PRO-ADD successfully identifies the optimal dose, balancing efficacy and tolerability.
  • The framework avoids escalating doses that offer no additional efficacy benefit.
  • PRO-ADD demonstrates effectiveness in finding the most tolerable effective dose.

Conclusions:

  • Patient-centric dose-finding approaches incorporating PROs are essential for advancing oncology.
  • PRO-ADD provides a robust framework for optimising dosage in modern oncology trials.
  • This methodology will shape the future of dose-finding studies for novel cancer therapies.
Keywords:
Patient-reported outcomesdose-finding trialsdose-optimisationoptimal biological dosephase I

More Related Videos

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts10:27

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts

Published on: July 25, 2020

6.5K
Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids08:52

Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids

Published on: November 22, 2021

6.0K

Related Concept Videos

Dosage Regimens: Designs and Approaches01:28

Dosage Regimens: Designs and Approaches

Designing a dosage regimen, which refers to the manner of drug administration, is a complex process involving the selection of drug dose, route, and frequency. This process is underpinned by pharmacokinetic parameters derived from tests and population averages. These parameters are then tailored to patient-specific variables such as diagnosis, demographics, and allergy status. Once therapy commences, therapeutic response monitoring is critical and achieved through clinical and physical...
600
Dosage Regimens: Partial Pharmacokinetic Parameters01:01

Dosage Regimens: Partial Pharmacokinetic Parameters

It is not uncommon for complete drug pharmacokinetic profiles to remain elusive in pharmacokinetics. This necessitates certain educated assumptions by pharmacokineticists to determine appropriate dosage regimens without comprehensive pharmacokinetic data from animal or human studies. One prevalent assumption is setting the bioavailability factor, denoted as F, to 1 or 100%. This assumption caters to the scenario where a drug doesn't achieve full systemic absorption, resulting in the patient...
363
Dosage Regimen: Individualization01:24

Dosage Regimen: Individualization

Individualization in dosing regimens is the customization of medication doses for individual patients. Its necessity arises from the goal of maximizing therapeutic benefits while minimizing risks. This approach is pivotal because human responses to drugs can vary widely; what is effective for one person may be inadequate or excessive for another. Interpatient (intersubject) variability refers to differences in drug responses between individuals, while intrapatient (intrasubject) variability...
398
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...
4.7K
Bioavailability Study Design: Healthy Subjects Versus Patients01:15

Bioavailability Study Design: Healthy Subjects Versus Patients

Bioavailability studies are essential for evaluating a drug's therapeutic efficacy and understanding its absorption patterns under various physiological conditions. Conducting such studies on target patient populations provides more relevant data by simulating real-world disease states. However, practical challenges often necessitate the use of young, healthy adult volunteers as study subjects.Patients may exhibit altered drug absorption patterns due to the effects of the disease itself,...
248
Impact of Pharmacokinetic–Pharmacodynamic Models: Regulatory Decisions01:15

Impact of Pharmacokinetic–Pharmacodynamic Models: Regulatory Decisions

PK–PD modeling has significantly influenced FDA regulatory decisions, particularly drug approval, dosage optimization, and labeling. These models integrate pharmacokinetics (PK) and pharmacodynamics (PD) to predict drug behavior and effects, aiding in optimizing dosing regimens and enhancing the probability of clinical trial success.One notable example is Nesiritide (Natrecor®), a recombinant human brain natriuretic peptide for treating acute decompensated congestive heart failure...
97