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MRC Capacity Building Studentship

Quantitative methods for the assessment of systematic error in observational studies: improving causal research.


Supervisors: Bianca De Stavola and Simon Cousens

Results from epidemiological studies often appear contradictory, leading to some cynicism regarding medical research among the general public. Many of these contradictions are attributable to the inadequate reporting of the uncertainties that affect this type of research.

Uncertainty arising from random sampling variation is typically the only uncertainty presented (in the form of confidence intervals). There are, however, other sources of uncertainty which may dwarf the uncertainty due to sampling variation. The extent of such uncertainties will vary from study to study but in general they arise from:

(i) unmeasured factors in the study population that are related to both outcome and exposure of interest ("unmeasured confounding");

(ii) non-random inclusion of subjects ("selection bias");

(iii) inaccuracies in measurements of outcome(s) and exposure(s) ("measurement error")

(iv) absence of outcome/exposure data for some subjects ("missing data").

The failure to consider properly these other sources of uncertainty has two negative consequences. First, results of studies are presented in a way which implies more certainty about them than is justified, increasing the likelihood of subsequent "contradictory" findings. Second, considering only uncertainty due to random sampling variation leads to the perception that increasing the study size will be sufficient to deal with uncertainty. Indeed data from different studies are now often merged ("pooled") with the stated aim of obtaining "more precise" estimates.

To improve understanding of research results and retain public trust, we must provide more realistic assessments of the uncertainties involved. Recently, new approaches to this problem have been proposed, but these approaches are not immediately accessible to practitioners, as they face difficulties that are both operational (e.g. how to specify the likely magnitude of selection bias) and methodological (e.g. how to combine this information with the observed data). The proposed PhD will investigate three alternative approaches to improved quantification of uncertainty; classical sensitivity analysis; Monte Carlo sensitivity analysis and Bayesian bias analysis. The feasibility of these approaches will be investigated in different contexts. The PhD should result in practical guidelines on methods which provide robust outputs while being transparent and accessible to a wide range of practitioners.