Use of multiple inflammatory marker tests in primary care: using Clinical Practice Research Datalink to evaluate accuracy

Jessica Watson; Hayley E Jones; Jonathan Banks; Penny Whiting; Chris Salisbury; Willie Hamilton

doi:10.3399/bjgp19X704309

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Repeat inflammatory marker testing - authors reply
Jessica Watson, Chris Salisbury, Penny Whiting, Jonathan Banks and Willie Hamilton

Published on: 15 November 2019
Use of multiple inflammatory marker tests in primary care: using Clinical Practice Research Datalink to evaluate accuracy
Ibrahim Hassan

Published on: 05 November 2019
Only part of a cascade
Peter von Kaehne

Published on: 03 July 2019

Published on: (15 November 2019)

Repeat inflammatory marker testing - authors reply
Jessica Watson, GP and NIHR Doctoral Research Fellow, University of Bristol
Other Contributors:
Chris Salisbury, Professor of Primary Health Care, University of Bristol

Penny Whiting, Associate Professor in Clinical Epidemiology, University of Bristol

Jonathan Banks, Research Fellow, University of Bristol

Willie Hamilton, Professor of Primary Care Diagnostics, University of Exeter
Thank you to Hassan for pointing out the importance of taking into account the trend in inflammatory markers when interpreting test results. In table 1 of the linked paper¹ we were able to look at the impact of repeat testing, and we can share further details of this analysis for clarification. Patients with an initial raised inflammatory marker which subsequently returned to normal had a lower overall incidence of disease at 18.6% compared to those with persistently raised inflammatory markers where overall disease incidence was 23.8%. Subdividing further for the most commonly used test, CRP, we found that a second abnormal test which is higher than the first (rising trend) had the highest overall disease incidence at 26.6%; those with a second abnormal test which was lower than the first but still above the upper limit of normal (stable or falling trend) had a dise...
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Thank you to Hassan for pointing out the importance of taking into account the trend in inflammatory markers when interpreting test results. In table 1 of the linked paper¹ we were able to look at the impact of repeat testing, and we can share further details of this analysis for clarification. Patients with an initial raised inflammatory marker which subsequently returned to normal had a lower overall incidence of disease at 18.6% compared to those with persistently raised inflammatory markers where overall disease incidence was 23.8%. Subdividing further for the most commonly used test, CRP, we found that a second abnormal test which is higher than the first (rising trend) had the highest overall disease incidence at 26.6%; those with a second abnormal test which was lower than the first but still above the upper limit of normal (stable or falling trend) had a disease incidence of 22.3%. This is in keeping with Hassan’s expectation that interpreting results in the context of previous test results provides additional information. However, clinicians should not be excessively reassured by repeat testing; patients with a repeat test which returns to normal have a higher overall disease incidence (18.6%), compared to patients with a raised inflammatory marker which was not repeated (12.5%). This presumably reflects the fact that the GPs decision to repeat the test meant they were suspicious that the patient was ill. This is in keeping with other research showing that the GPs decision to test may be more predictive than the test result.²

References

1. Watson J, Salisbury C, Whiting P, Banks J, Pyne Y, Hamilton W. Added value and cascade effects of inflammatory marker tests in UK primary care: a cohort study from the Clinical Practice Research Datalink. Br J Gen Pract 2019; 69(684): e470-e478. DOI: 10.3399/bjgp19X704321

2. Watson J, Bailey S, Hamilton F, Hamilton W, Mounce L. Lessons from biases in electronic health record data: the importance of clinical vigilance with negative test results. BMJ (letter). Available at www.bmj.com/content/361/bmj.k1479/rr-0.

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Competing Interests: None declared.
Published on: (5 November 2019)

Use of multiple inflammatory marker tests in primary care: using Clinical Practice Research Datalink to evaluate accuracy
Ibrahim Hassan, GP Partner, Sandringham Practice, Intake, Doncaster
Thanks to Jessica Watson et al¹ for their very useful research paper. This touches on one aspect of the very topical issue of over investigation. This is a real problem which sometimes gives the impression that investigations are used as a substitute to a thorough history and examination.

I would like to know if for the purposes of this research, when assessing the predictive value of current raised inflammatory markers,...
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Thanks to Jessica Watson et al¹ for their very useful research paper. This touches on one aspect of the very topical issue of over investigation. This is a real problem which sometimes gives the impression that investigations are used as a substitute to a thorough history and examination.

I would like to know if for the purposes of this research, when assessing the predictive value of current raised inflammatory markers, the results of previous inflammatory markers have been compared with current one.

This is because for a patient who has had inflammatory marker checked previously, a current high level of that inflammatory markers that is within the range of their previous levels is likely to be less predictive of relevant disease compared to a high level which is significantly higher than their previous levels.

Therefore, while I agree with the conclusion, however in patients who have had previous inflammatory markers, interpretation of significance of a current test result taking into account the previous levels should increase ability to rule out (new/worsening) relevant disease.

Reference

1. Watson J, Jones HE, Banks K et al. Use of multiple inflammatory marker tests in primary care: using Clinical Practice Research Datalink to evaluate accuracy. Br J Gen Pract 2019;69(684):e462-e469.

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Competing Interests: None declared.
Published on: (3 July 2019)

Only part of a cascade
Peter von Kaehne, General practitioner, Lochgoilhead Medical Centre
While being a useful reminder that sick folk can have normal tests and vice versa, the article misses the point that many (most?) GPs will use inflammatory markers as the concluding part of a cascade, not the begin and end of it.

A patient with an unconcerning history, normal examination findings and normal inflammatory markers is a patient with a high likelihood of being actually well. In absence of sharper tests for being physically well (even if worried) such cascades remain the norm and rightly so for filtering the sick or potentially sick from those we can reassure. On the other side, worry...
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While being a useful reminder that sick folk can have normal tests and vice versa, the article misses the point that many (most?) GPs will use inflammatory markers as the concluding part of a cascade, not the begin and end of it.

A patient with an unconcerning history, normal examination findings and normal inflammatory markers is a patient with a high likelihood of being actually well. In absence of sharper tests for being physically well (even if worried) such cascades remain the norm and rightly so for filtering the sick or potentially sick from those we can reassure. On the other side, worrying findings or history are clearly not assuaged by a normal CRP on its own.

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Competing Interests: None declared.