Developing a Core Outcome Set (COS) for early phase trials in mechanically ventilated patients

Many phase 3 clinical trials in critical care show no effect; one reason for this is that beneficial effects of outcome measures used in early phase clinical trials are used to design the subsequent phase 3 trials and they may not be good representatives of the real clinical outcome. These outcome measures include surrogate measures. A surrogate endpoint is a measurement of a specific outcome which is considered to be a valid predictor (or representative) of the real outcome or final result. It is a factor or a covariate that is known (or highly suspected) in the causal pathway of the patient centred outcome. The validity of a surrogate measure is very hard to prove for various reasons. A single measure, the primary outcome measure, is generally used to inform the design of a study and the power calculation. A number of outcomes that can provide a complete evaluation of the patient status to predict the long term outcome should be considered better than a single outcome measure in early phase trials. Currently, there is uncertainty regarding which outcomes should be used in early phase trials for the mechanically ventilated patient population. We aim to develop a COS for early phase critical care trials that is responsive to predicting end point (real) outcomes.

This COS is for all critical care interventions.

Contributors

Ms. Rejina Mariam Verghis, Queen’s University Belfast (Ph.D Student)
Dr. Bronagh Blackwood, Centre for Infection and Immunity, Queen’s University Belfast (Principal Supervisor)
Mrs. Cliona McDowell, Northern Ireland Clinical Trials Unit
Prof. Daniel F. McAuley, Centre for Infection and Immunity, Queen’s University Belfast
Prof. Mike Clarke, All-Ireland Hub for Trials Methodology Research, Centre for Public Health, Queen’s University Belfast, , Belfast, UK

Further Study Information

Current Stage: Completed – pending publication
Date: March 2015 - February 2018
Funding source(s): This study is funded through a Doctoral Research Fellowship grant from the Northern Ireland Clinical Trials Unit


Health Area

Disease Category: Lungs & airways

Disease Name: Acute lung injury (ALI), Mechanical ventilation

Target Population

Age Range: 16 - 100

Sex: Either

Nature of Intervention: Mechanical ventilation

Stakeholders Involved

- Clinical experts
- Economists
- Methodologists
- Researchers
- Statisticians

Study Type

- COS for clinical trials or clinical research

Method(s)

- Consensus meeting
- Other
- Systematic review

1. We plan to conduct a systematic review of the literature for critical care trials. We will specifically look for and include phase 2 trials and extract information on the outcome measures they used. We will also include any resulting phase 3 trials that followed the phase 2 trial.
2. We will undertake statistical modelling of surrogate outcomes from phase 2 trials to determine which surrogates are more reliable predictors of the real (long term) outcome (we acknowledge that we may not be able to test some surrogates if we do not also have data on longer term outcomes)
3. Consensus meeting to agree a core outcome set for early phase critical care trials.

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