“Screening: a wasteful use of resources?” Onno van Schayck, Maastricht University The Netherlands IPCRG, May 26, Amsterdam, The Netherlands

Why should we find patients with COPD? Is it useful or wasteful? If useful, what is the most efficient and effective way in finding COPD cases?

Underdiagnosis of COPD How big is the problem of underdiagnosis of COPD? Several studies in the world indicate that the problem of underdiagnosis is still big

What could be the possible reasons for the underdiagnosis of COPD? Underdiagnosis by GPs or other physicians Underpresentation of symptoms by patients Underperception of symptoms by patients

General population (n=1150) Obstruction + symptoms (n=86) Schayck CP van et al. Thorax 2000;55:562-5

Subjects with obstruction and symptoms (n=86) 7% Schayck CP van, et al. Thorax 2000;55:562-565

Subjects who presented symptoms (n=29) 34% Schayck CP van, et al. Thorax 2000;55:562-565

So, who is to blame? The GP or the patient?

Probably both. But the main reason for underdiagnosis is underpresentation of symptoms by the patient.

Perception of dyspnoea? What could be the reason? Perception of dyspnoea?

PERCEPTION OF DYSPNOEA Method described by Brand et al. (Am Rev Respir Dis 1992;146P:396-401) Degree of dyspnoea scored on Borg scale during Histamine provocation test Good perceivers: Decrease in FEV1 is accompanied by increase in Borg scale

Are there other characteristics that can explain presenting symptoms to the GP or not?

1 Clinically relevant difference Mean Difference Did consult GP (n=99) Did not consult GP (n=267) F Sign. CRQ: Dyspnoea .651 5.89 6.54 20.78 p<.001 CRQ: Emotions .31 5.25 5.56 6.56 .011 CRQ: Fatigue .561 4.97 5.53 14.49 CRQ: Mastery .25 6.48 6.73 9.67 .002 1 Clinically relevant difference Boom G van den, et al. Eur Respir J 1998;11:67-72

1 Clinically relevant difference Mean Difference Did consult GP (n=99) Did not consult GP (n=267) F Sign. CRQ: Dyspnoea .651 5.89 6.54 20.78 p<.001 CRQ: Emotions .31 5.25 5.56 6.56 .011 CRQ: Fatigue .561 4.97 5.53 14.49 CRQ: Mastery .25 6.48 6.73 9.67 .002 1 Clinically relevant difference Boom G van den, et al. Eur Respir J 1998;11:67-72

1 Clinically relevant difference Mean Difference Did consult GP (n=99) Did not consult GP (n=267) F Sign. CRQ: Dyspnoea .651 5.89 6.54 20.78 p<.001 CRQ: Emotions .31 5.25 5.56 6.56 .011 CRQ: Fatigue .561 4.97 5.53 14.49 CRQ: Mastery .25 6.48 6.73 9.67 .002 1 Clinically relevant difference Boom G van den, et al. Eur Respir J 1998;11:67-72

But probably many patients do not want to know that they have symptoms. They simply deny symptoms as they do not want to stop smoking. ⇒ Cognitive dissonance

Also the physician is convinced that the disease is self-inflicted due to smoking which closes the vicious circle

Is such an identification really efficient? A question which is often asked is: Can you identify COPD in smokers? Is such an identification really efficient?

How many smokers have COPD? Lung Health Study 7300 smokers 35-60 years 30% had obstruction Connett et al. Contr Clin Trial 1993

How many smokers have COPD? Polish Study 11.000 smokers > 40 years 25% had obstruction Zielinski, Chest 2001

Didasco study (screening of smokers and non-smokers) in Belgium Early detection of COPD in general practice. All patients 35-70 year were screened and 925 subjects performed spirometry Totally 7.4% had an obstruction Buffels et al, Chest 2004

In the Didasco study, no preselection on the basis of smokers was made. This method is rather time-consuming for general practice.

The implementation of screening in primary care is difficult and case-finding on the basis of smoking is likely to be a more suitable approach in this setting.

Case finding of COPD in general practice The aim of the study was to investigate how effective case finding of subjects with a high risk for COPD (i.e. smokers) is as a method. van Schayck et al. BMJ 2002;324:1370-3

Method Two semi-rural general practices, 651 randomly selected persons aged 35 to 70 years were studied. Current smokers among these subjects who were not yet on pulmonary medication were asked to complete a short standardised questionnaire on bronchial symptoms.

Schayck CP van, et al. BMJ 2002;324:1370-3 Chance of having obstruction (FEV1<80%) in smokers with or without cough with increasing age Schayck CP van, et al. BMJ 2002;324:1370-3

< 16.5 low risk 16.5 – 19.5 increased risk > 19.5 high risk Symptom-Based Questionnaire for Identifying COPD in Smokers David B. Price, David G. Tinkelman, R.J. Halbert, Robert J. Nordyke, Sharon Isonaka, Dmitry Nonikov, Elizabeth F. Juniper, Daryl Freeman, Thomas Hausen, Mark L. Levy, Anders Østrem, Thys van der Molen, Constant P. van Schayck Respiration 2006;73:285–295 DOI: 10.1159/000090142 < 16.5 low risk 16.5 – 19.5 increased risk > 19.5 high risk

CDQ validation studies compared with original study Number recruited for study Number analysed Price et al., 2006 898 818 Kotz et al., 2008 826 676 Kawayama et al., 2008 169 Sichletidis et al., 2011 1250 1078 Frith et al., 2011 233 201 Stanley et al., 2014 1631 1054

Performance of COPD Diagnostic Questionnaire across comparison studies Study Cut-off point (16.5) Sensitivity (%) Specificity (%) Price et al., 2006 80.4 57.5 Kotz et al., 2008 89.2 24.4 Kawayama et al., 2008 93.9 40.4 Sichletidis et al., 2011 91 49 Frith et al., 2011 37 Stanley et al., 2014 79.7 46.8

COPD Diagnostic Questionnaire (CDQ) for selecting at-risk patients for spirometry: a cross-sectional study in Australian general practice Anthony J Stanley, Iqbal Hasan, Alan J Crockett, Onno C P van Schayck & Nicholas A Zwar Npj Primary Care Respiratory Medicine (2014) 24, 14024; doi: 10.1038/npjpcrm.2014.24; published online 10 July 2014

Receiver operating characteristic (ROC) curve comparing the COPD Diagnostic Questionnaire score to chronic obstructive pulmonary disease diagnosis. Cut point 16.5—grey star; 19.5—black star. A ROCauc of 0.5 is indicated by the solid diagonal line.

The literature suggests that a cut point with the best balance between sensitivity and specificity based on the ROC curve is considered best at discriminating between diseased and non-diseased cases. In this study, using these methods would result in 19.5 being the optimal cut point. However, this has a sensitivity of only 63% and 37% of COPD diagnoses would be missed. To some clinicians, this would be considered an unacceptably high rate of missed COPD diagnoses.

Performance of CDQ at different cut points Abbreviation: CDQ, COPD Diagnostic Questionnaire. Sensitivity Specificity Positive predictive value (%) Negative predictive value (%) Patients below the cut point (%) 9.5 0.978 0.099 14.1 96.8 8.9 10.5 0.964 0.126 14.3 95.9 11.4 11.5 0.190 15.2 97.2 17.0 12.5 0.935 0.228 15.4 20.7 13.5 0.928 0.278 16.2 96.2 25.1 14.5 0.906 0.346 17.3 96.1 31.3 15.5 0.833 0.412 17.6 94.2 38.0 16.5 0.797 0.468 18.4 93.9 43.4 17.5 0.768 0.552 20.5 94.0 51.0 18.5 0.674 0.644 22.2 92.9 60.2 19.5 0.630 0.701 24.1 92.6 65.7 0.572 0.743 92.0 70.2 21.5 0.471 0.823 28.6 91.2 78.5 22.5 0.355 0.864 28.2 89.9 83.5 23.5 0.297 0.893 29.4 89.4 86.8 24.5 0.196 0.927 28.8 88.4 91.1

A cut point of 14. 5 is proposed, because of its high sensitivity (90 A cut point of 14.5 is proposed, because of its high sensitivity (90.6%) and high negative predictive value (96%). At the same time, 31% of patients in the low likelihood group do not need to undergo spirometry. For example, choosing a 12.5 cut point would lead to a ~3% increase in sensitivity but would require 10% more spirometries than a 14.5 cut point (21 vs 31% patients below cut point).

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Early detection of COPD in general practice: patient or practice managed? A randomised controlled trial of two strategies in different socioeconomic environments Joseph AM Dirven, Huibert J Tange, Jean WM Muris, Karin MA van Haaren, Gerrit Vink, Onno CP van Schayck Primary Care Respiratory Journal 2013; 22(3): 331-337 http://dx.doi.org/10.4104/pcrj.2013.00070

Aims: To compare the effectiveness of two strategies for population-based early detection of COPD, taking into account different socioeconomic status (SES) settings. Methods: In the practice-managed condition, the practice was responsible for the whole procedure, while in the patient-managed condition, patients were responsible for calculating their CDQ risk score and applying for a spirometry test. The main outcome measure was the rate of COPD diagnoses after screening.

Results of the CDQ and spirometry test by strategy and socioeconomic status (SES) Results (by SES setting) Patient-managed strategy Practice-managed strategy All practices CDQ distributed 6,393 3,715 Responders (% of distributed) 1,715 (27%) 1,855 (50%) High risk on CDQ (% of responders) 186 (11%) 251 (14%) Show up for spirometry (% of high riks) 140 (75%) 135 (54%) COPD diagnosis (% of show up) 25 (18%) 48 (36%) COPD diagnoses in a standard practice 3.0 8.9

Costs to detect one COPD diagnosis in a standard Dutch practice (2350 patients) in low SES vs moderate to high SES practices Start condition (by SES setting) Patient-managed Practice-managed All practices Cost per detected case € 698 € 256 Low SES practices € 512 € 224 Moderate to high SES practices € 926 € 324 Cost per unit: €2 for a CDQ, €28 for a spirometry test (in case of high risk) and €18 for a COPD consultation (in case of positive diagnosis) SES = socioeconomic status

Perceived barriers and facilitators and health provider satisfaction The barriers for successful implementation: ethnicity absence of financial compensation limited supporting staff. No barriers were perceived in the nature of the programme itself or in the qualifications of the care providers.

Conclusions An important reason for underdiagnosis is the underpresentation of symptoms by the patient. Case finding of COPD in primary care on the basis of presented symptoms in smokers is effective and efficient. CDQ has shown to have a relatively high sensitivity in several validation studies in different parts of the world. CDQ is not appropriate to discriminate between diseased and non-diseased cases, but is highly effective and efficient to select smokers for spirometry in order to diagnose COPD. A practice managed strategy in which the GP takes the initiative to invite patients leads to three times more detection of COPD cases costing less than half the money compared to patients taking the initiative.