Efficient designs for clinical trials

Lead Research Organisation: University of Cambridge

Abstract

The development of new medicines and health technologies is lengthy and expensive and many development programmes turn out to be unsuccessful. Unfortunately when such a development fails it is often late in the process so that large numbers of participants are exposed to ineffective or possibly harmful treatments. At the same time substantial resources have been invested to reach this point.
This research develops novel statistical methods to design clinical trials that yield faster and / or more accurate conclusions about the potential of an intervention. This includes establishing the optimal dose and frequency of dosing as well as the safety and efficacy of a medicine or health technology. This is achieved by using accumulating data within a study to allow early decisions about important aspects such as dose or efficacy as well as through augmenting trial data with relevant external information such as other trials in different patient populations.

Technical Summary

Clinical trials are essential to establish the best regimen (dose, duration of treatment, frequency of treatment, …) of an intervention and randomized controlled trials are the gold standard to evaluate the potential efficacy and safety of a medicine or health technology.
The increasing cost of clinical trials as well as the high attrition rate during the development mean, however, that new design and analysis methods to increase efficiency are greatly needed. The challenge is to seek improvements throughout the drug development process to eliminate ineffective or harmful treatments quickly and provide better estimates of the optimal dose for treatments which in turn will reduce the number of unsuccessful late stage clinical trials and allow for more efficient development of medicinal products and health technologies overall. In parallel, barriers to implementation of these novel efficient designs need to be broken down and to achieve this, close interaction with clinical experts and the pharmaceutical industry in particular is paramount.
Mathematically the focus of the research is sequential and adaptive decision making based on accumulating data and the closely related topic of multiple testing.
My proposed future work includes five main objectives:
1. Bayesian adaptive dose-finding trials with multiple objectives;
2. adaptive designs in small populations;
3. estimation after adaptive trials;
4. adaptive trials for infectious diseases;
5. treatment development in heterogeneous populations.

Publications

10 25 50

publication icon
Dodd LE (2020) Endpoints for randomized controlled clinical trials for COVID-19 treatments. in Clinical trials (London, England)

publication icon
Jackson H (2021) Using biomarkers to allocate patients in a response-adaptive clinical trial in Communications in Statistics - Simulation and Computation

 
Description AGILE: Seamless Phase I/IIa Platform for the Rapid Evaluation of Candidates for COVID-19 treatment
Amount £3,284,097 (GBP)
Funding ID MR/V028391/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 01/2021 
End 01/2023
 
Description AGILE: Seamless Phase I/IIa Platform for the Rapid Evaluation of Candidates for COVID-19 treatment
Amount £3,069,077 (GBP)
Funding ID 221590/Z/20/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 02/2021 
End 01/2023
 
Description An adaptive randomized controlled trial to reduce mortality and readmission among children with HIV and severe acute malnutrition in sub-Saharan Africa
Amount £5,000,000 (GBP)
Funding ID NIHR201813 
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 08/2021 
End 08/2025
 
Description Building Data Rich Clinical Trials
Amount € 5,999,411 (EUR)
Funding ID 965397 
Organisation European Commission H2020 
Sector Public
Country Belgium
Start 02/2021 
End 01/2025
 
Description HElping Alleviate the Longer-term consequences of COVID-19 (HEAL-COVID): a national platform trial
Amount $3,583,669 (USD)
Funding ID NIHR133788 
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 02/2021 
End 01/2024
 
Description Adaptive designs MUW 
Organisation Medical University of Vienna
Department Centre for Medical Statistics, Informatics and Intelligent Systems
Country Austria 
Sector Academic/University 
PI Contribution Joint research
Collaborator Contribution Joint research
Impact Publications.
Start Year 2011
 
Description Institute Gustave Roussy (Paris) 
Organisation Gustave-Roussy Institute
Country France 
Sector Academic/University 
PI Contribution Joint research on dose-finding. Research visits
Collaborator Contribution Joint research
Impact Publications
Start Year 2016
 
Description Janssen 
Organisation Janssen Pharmaceutica NV
Country Belgium 
Sector Private 
PI Contribution Joint reseach, support for studies, training
Collaborator Contribution Joint research, data
Impact Publications
Start Year 2017
 
Description Lee New Mexico 
Organisation University of New Mexico
Country United States 
Sector Academic/University 
PI Contribution Joint research
Collaborator Contribution Novel methods for PITE
Impact Publications
Start Year 2014
 
Description Liverpool 
Organisation University of Liverpool
Department Department of Molecular and Clinical Pharmacology
Country United Kingdom 
Sector Academic/University 
PI Contribution Joint research
Collaborator Contribution Input into research and practical perspective.
Impact Joint publications
Start Year 2015
 
Description Merck 
Organisation Merck
Country Germany 
Sector Private 
PI Contribution Joint research, training
Collaborator Contribution Joint research
Impact None so far
Start Year 2017
 
Description Peter Horby 
Organisation University of Oxford
Country United Kingdom 
Sector Academic/University 
PI Contribution Joint research on trials during epidemics. Statistical expertise
Collaborator Contribution Joint research on trials during epidemics. Expertise in infectious diseases
Impact Joint publications
Start Year 2016
 
Description Torino 
Organisation Polytechnic University of Turin
Country Italy 
Sector Academic/University 
PI Contribution Joint research and visits
Collaborator Contribution Joint research
Impact Publications
Start Year 2016
 
Description Cambridge Science Festival 2021 - 'How to find treatments during a pandemic' 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Thomas Jaki gave virtual talk for Cambridge Science Festival 2021 on the topic of 'How to find treatments during a pandemic'. Talk included polls for audience to take part in.
Year(s) Of Engagement Activity 2021
 
Description HDR-UK meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Webinar as part of HDR-UK series
Year(s) Of Engagement Activity 2021
 
Description IDweek 2021 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presentation with panel discussion on issues of trial design for COVID-19
Year(s) Of Engagement Activity 2021
 
Description JSM2021 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Discussion panel on COVID clinical trials at JSM
Year(s) Of Engagement Activity 2021
 
Description PSI Onco Webinar 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Webinar with discussion panel with PSI
Year(s) Of Engagement Activity 2021
 
Description ROES 2021 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited presentation on on dose-finding studies
Year(s) Of Engagement Activity 2021
 
Description Talk for Biotech-pharma Statistics Workshop 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact Thomas Jaki invited to give talk on 'Designing efficient clinical trials during a pandemic: Some personal lessons from the RECOVERY trial' for the Biotech-pharma Statistics Workshop
Year(s) Of Engagement Activity 2020
 
Description Talk for Brown University 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Study participants or study members
Results and Impact Thomas Jaki invited to give talk for Brown University, USA on 'An information-theoretic approach for selecting arms in clinical trials'
Year(s) Of Engagement Activity 2020
 
Description Talk for Columbia University 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Study participants or study members
Results and Impact Thomas Jaki invited to give talk for Columbia University, USA on 'Designing clinical trials during a pandemic: Some personal lessons from COVID-19'
Year(s) Of Engagement Activity 2020
 
Description Talk for HTMR annual meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact Thomas Jaki invited to give talk on 'Designing clinical trials during a pandemic: Some personal lessons from COVID-19' at the HTMR annual meeting
Year(s) Of Engagement Activity 2020
 
Description Talk for PHASTAR Life Science Summit 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact Thomas Jaki invited to give talk on 'Designing clinical trials during a pandemic' for the PHASTAR Life Science Summit
Year(s) Of Engagement Activity 2020
 
Description Talk for WHO TB technical consultation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact Thomas Jaki invited to give talk on 'Finding the right duration using multi-arm multi-stage designs' for the WHO TB technical consultation
Year(s) Of Engagement Activity 2020