Abstract
Dear Sir,
We would like to respond to Fraser's letter regarding our recent publication. 1
Fraser is correct in highlighting that health is a devolved matter in the UK. Therefore, in the paper, we should have specifically referred to bowel cancer screening in England rather than the UK. However, in the context of the article the point is largely irrelevant; as all such programmes are funded by the NHS.
He describes our experiment to assess analytical sensitivity/analytical detection limit (ADL) as being flawed. While he is correct in highlighting that ‘occult blood-negative’ does not mean that there is no such material present, his critique of our experiment and its’ conclusions is confused and mathematically incorrect.
Consider, for example, that the ‘base’ sample contained an equivalent of 0.2 mg Hb/g matrix. If one then adds a spike of 0.4 mg Hb/g matrix to that material, giving a concentration equivalent to 0.6 mg Hb/g matrix then an assay system with claimed detection limit of 0.6 mg Hb/g matrix (i.e. hema-screen FOBT, Immunostics Inc, Sunset Avenue, Ocean, NJ, USA) should become positive at that concentration. Instead, in our experiment, the test only became positive when we had supplemented the base sample with an additional 0.7 mg Hb/g matrix, which would therefore mean the matrix contained 0.9 mg Hb/g. Therefore our observed ‘sensitivity’/ADL of 0.7 mg Hb/g matrix is an optimistic one and the ‘true’ limit of detection could be even higher than we suggest, and not lower as Fraser implies. Importantly the NHS purchasing and supply agency in their evidence-based purchasing report, also observed a limit of detection of ≥0.9 mg Hb/g matrix. 2
Fraser argues that a dichotomous test should only be positive at the detection limit 50% of the time and suggests that over a range of concentrations of haemoglobin in samples circulated by the Yorkshire External Quality Assessment Scheme (YEQAS) that the percentage positives and negatives when plotted on the ordinate against concentration on the abscissa will demonstrate an intersection point at a concentration equivalent to the ADL. This makes the invalid assumption that the 17.2% of participants unable to detect a challenge of 1.2 mg Hb/g matrix in the YEQAS faecal occult blood (FOB) scheme are unable to do so simply because of analytical variability. Alternative explanations for these false-negatives may include storage/stability problems, internal quality control problems or training issues. Fraser fails to appreciate this and uses the data to legitimize the manufacturers’ claimed detection limit.
Fundamentally, he seems to have missed the entire point of our publication – i.e. to verify that our reporting and interpretations of the occult blood test were robust and reliable; and our experiment proves that irrefutably.
We agree with him that cost should not be an overriding consideration or justification in selection of any methods used in clinical laboratories. However, it is noteworthy that of 182 users registered on the YEQAS only six (3.3%) seem to use an immunological-based occult blood method (2009 data), illustrating the budgetary constraints that may prevent laboratories migrating to a significantly more expensive immunochemical assay.
Lastly, Fraser restates his personal opinion 3 that FOB testing, outside of a bowel cancer screening programme should be abandoned. While that opinion might not be shared by all, as 182 users/laboratories continue their participation in the YEQAS programme, presumably undertaking occult blood testing out with screening programmes, the highlighting of this issue does serve as a timely reminder for laboratories to reconsider their position.
DECLARATIONS