This workstream brings together
leading health economists, methodologists and statisticians from Leeds,
Birmingham and Oxford and aims to develop methodology to evaluate the optimal
use and benefits of biomarkers for patient and disease monitoring in three
- Methodological review work to identify areas of research
that could be developed or adapted for use in monitoring for disease
progression or recurrence. This includes the examination of case studies for insight
into current practice in monitoring for progression or recurrence, the review
of existing randomised controlled trials (RCTs) of monitoring, and also the
review of available methodology to
identify areas of research that could be used or adapted for development
and evaluation of monitoring strategies.
- How simulation
models can be used to design and evaluate monitoring rules, particularly how
information from an ongoing study can be used to adapt and optimise the design
of that study. The reliability of a simulation model depends on the data upon
which it is based. This stage will consider the way in which information obtained
during an on-going study (the ELUCIDATE trial – workstream 3) can be analysed
to optimise monitoring rules, and whether resulting adaptations for the design
for the on-going study can be implemented without compromising its validity or
- Health economics –
optimising monitoring tests to meet a cost-effectiveness decision rule;
characterising cost-effectiveness of diagnostic tests for resource allocation
decisions; and assessing the value of further research.
Information and results arising from this important line of
work is then used to feed back to the other workstreams, particularly workstream
3 – the ELUCIDATE trial, to provide guidance for future approaches.Progress to Date
- methodological reviews have found that RCTs are characterised by lack
of power, issues with study validity and lack of compliance with prescribed
monitoring strategies both by patients and by clinicians. Monitoring strategies
are complex interventions and, as such, can influence patient outcome in a
multitude of ways, both expected and unanticipated. Furthermore limited
attention has been paid to basic features of measurement and measurement error.
A new CONSORT extension may be required to improve standards
- following examinations of case studies, such as PSA for monitoring of
prostate cancer, it is clear that there is limited evidence of the use of
systematic methodologies to develop monitoring strategies
simulation studies are
being used to identify optimal strategies in terms of test schedules and
decision rules, and emphasise that net health benefit at the population
level should be an important part of the justification of any particular case
definition threshold. A formal decision analytic approach can be used to
identify the threshold that optimizes the contribution of these technologies to
population health in a given health care system.
Longo R, Baxter P, Hall P, Hewison J, Afshar M, Hall G, McCabe C. Methods for identifying the cost effective case definition
threshold for sequential monitoring tests: an extension of Phelps and Mushlin.
PharmacoEconomics. 2014; 32:327-334.
- Dinnes J, Hewison J, Altman D, Deeks J. The basis for
monitoring strategies in clinical guidelines: a case study of prostate specific
antigen for monitoring in prostate cancer. Canadian Medical Association Journal. 2012; 184(2):169-77.
- Dinnes J, Hewison J, Altman D, Deeks J. What can available
randomised controlled trials evaluating monitoring strategies tell us about the
design and analysis of future trials? Paper presented at MRC Clinical Trials
Methodology Conference, Bristol UK; Oct 4-5 2011.