. 2018 Dec 3;18(1):607.

doi: 10.1186/s12879-018-3515-9.

High heterogeneity in community-acquired pneumonia inclusion criteria: does this impact on the validity of the results of randomized controlled trials?

Clara Flateau¹, Josselin Le Bel^{2

3

4}, Sarah Tubiana^{3

4

5

6}, François-Xavier Blanc^{7

8

9

10}, Christophe Choquet^{6

11}, Blandine Rammaert^{12

13}, Patrick Ray^{14

15}, Christophe Rapp¹⁶, Cécile Ficko¹⁶, Catherine Leport^{3

4

6

17}, Yann-Erick Claessens¹⁸, Xavier Duval^{3

4

5

6}; ESCAPED study group

Collaborators, Affiliations

Collaborators

ESCAPED study group:
Y E Claessens, X Duval, E Bouvard, M F Carette, M P Debray, C Mayaud, C Leport, N Houhou, S Tubiana, M Benjoar, F X Blanc, A L Brun, L Epelboin, C Ficko, A Khalil, H Lefloch, J M Naccache, B Rammaert, A Abry, J C Allo, S Andre, C Andreotti, N Baarir, M Bendahou, L Benlafia, J Bernard, A Berthoumieu, M E Billemont, J Bokobza, E Burggraff, P Canavaggio, E Casalino, S Castro, C Choquet, H Clément, L Colosi, A Dabreteau, S Damelincourt, S Dautheville, M Delay, S Delerme, L Depierre, F Djamouri, F Dumas, M R S Fadel, A Feydey, Y Freund, L Garcia, H Goulet, P Hausfater, E Ilic-Habensus, M O Josse, J Kansao, Y Kieffer, F Lecomte, K Lemkarane, P Madonna, O Meyniard, L Mzabi, D Pariente, J Pernet, F Perruche, J M Piquet, R Ranerison, P Ray, F Renai, E Rouff, D Saget, K Saïdi, G Sauvin, E Trabattoni, N Trimech, C Auger, B Pasquet, S Tamazirt, J M Treluyer, F Tubach, J Wang, O Chassany, C Misse

Affiliations

¹ Service de Maladies Infectieuses, Centre Hospitalier de Melun, Melun, France. clara.flateau@ch-melun.fr.
² Département de Médecine Générale, Université Paris Diderot, Sorbonne Paris Cité, 75018, Paris, France.
³ Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
⁴ IAME - UMR 1137, Université Paris Diderot, Paris, France.
⁵ Inserm CIC 1425, Paris, France.
⁶ Hôpital Bichat Claude Bernard, Assistance Publique des Hôpitaux de Paris, Paris, France.
⁷ Service de Pneumologie, Institut du Thorax, CHU Nantes, Nantes, France.
⁸ Inserm, UMR1087, Institut du Thorax, Nantes, France.
⁹ CNRS, UMR 6291, Nantes, France.
¹⁰ Université de Nantes, Nantes, France.
¹¹ Service d'Accueil des Urgences, Hôpital Bichat Claude Bernard, Paris, France.
¹² Service de Maladies Infectieuses et Tropicales, CHU de Poitiers, Université de Poitiers, Poitiers, France.
¹³ Inserm U1070, Poitiers, France.
¹⁴ Service d'Accueil des Urgences, Hôpital Tenon, Hôpitaux Universitaires Est Parisien, Assistance Publique des Hôpitaux de Paris, Paris, France.
¹⁵ DHU "Fighting against ageing and stress" (FAST), UPMC Paris 6, Paris, France.
¹⁶ Service des Maladies Infectieuses, Hôpital d'Instruction des Armées Bégin, Saint-Mandé, France.
¹⁷ Unité de Coordination du Risque Epidémique et Biologique (COREB), Assistance-Publique Hôpitaux de Paris, Paris, France.
¹⁸ Department of Emergency Medicine, Centre Hospitalier Princesse Grace, Principality of Monaco, France.

PMID: 30509278
PMCID: PMC6276130
DOI: 10.1186/s12879-018-3515-9

High heterogeneity in community-acquired pneumonia inclusion criteria: does this impact on the validity of the results of randomized controlled trials?

Clara Flateau et al. BMC Infect Dis. 2018.

. 2018 Dec 3;18(1):607.

doi: 10.1186/s12879-018-3515-9.

Authors

Collaborators

ESCAPED study group:
Y E Claessens, X Duval, E Bouvard, M F Carette, M P Debray, C Mayaud, C Leport, N Houhou, S Tubiana, M Benjoar, F X Blanc, A L Brun, L Epelboin, C Ficko, A Khalil, H Lefloch, J M Naccache, B Rammaert, A Abry, J C Allo, S Andre, C Andreotti, N Baarir, M Bendahou, L Benlafia, J Bernard, A Berthoumieu, M E Billemont, J Bokobza, E Burggraff, P Canavaggio, E Casalino, S Castro, C Choquet, H Clément, L Colosi, A Dabreteau, S Damelincourt, S Dautheville, M Delay, S Delerme, L Depierre, F Djamouri, F Dumas, M R S Fadel, A Feydey, Y Freund, L Garcia, H Goulet, P Hausfater, E Ilic-Habensus, M O Josse, J Kansao, Y Kieffer, F Lecomte, K Lemkarane, P Madonna, O Meyniard, L Mzabi, D Pariente, J Pernet, F Perruche, J M Piquet, R Ranerison, P Ray, F Renai, E Rouff, D Saget, K Saïdi, G Sauvin, E Trabattoni, N Trimech, C Auger, B Pasquet, S Tamazirt, J M Treluyer, F Tubach, J Wang, O Chassany, C Misse

Affiliations

¹ Service de Maladies Infectieuses, Centre Hospitalier de Melun, Melun, France. clara.flateau@ch-melun.fr.
² Département de Médecine Générale, Université Paris Diderot, Sorbonne Paris Cité, 75018, Paris, France.
³ Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
⁴ IAME - UMR 1137, Université Paris Diderot, Paris, France.
⁵ Inserm CIC 1425, Paris, France.
⁶ Hôpital Bichat Claude Bernard, Assistance Publique des Hôpitaux de Paris, Paris, France.
⁷ Service de Pneumologie, Institut du Thorax, CHU Nantes, Nantes, France.
⁸ Inserm, UMR1087, Institut du Thorax, Nantes, France.
⁹ CNRS, UMR 6291, Nantes, France.
¹⁰ Université de Nantes, Nantes, France.
¹¹ Service d'Accueil des Urgences, Hôpital Bichat Claude Bernard, Paris, France.
¹² Service de Maladies Infectieuses et Tropicales, CHU de Poitiers, Université de Poitiers, Poitiers, France.
¹³ Inserm U1070, Poitiers, France.
¹⁴ Service d'Accueil des Urgences, Hôpital Tenon, Hôpitaux Universitaires Est Parisien, Assistance Publique des Hôpitaux de Paris, Paris, France.
¹⁵ DHU "Fighting against ageing and stress" (FAST), UPMC Paris 6, Paris, France.
¹⁶ Service des Maladies Infectieuses, Hôpital d'Instruction des Armées Bégin, Saint-Mandé, France.
¹⁷ Unité de Coordination du Risque Epidémique et Biologique (COREB), Assistance-Publique Hôpitaux de Paris, Paris, France.
¹⁸ Department of Emergency Medicine, Centre Hospitalier Princesse Grace, Principality of Monaco, France.

PMID: 30509278
PMCID: PMC6276130
DOI: 10.1186/s12879-018-3515-9

Abstract

Background: There is no consensus on the most accurate combination of diagnostic criteria to define community acquired pneumonia (CAP). We describe inclusion criteria in randomized controlled trials (RCT) of CAP and assess their performance for the diagnosis of formally identified CAP.

Methods: RCTs related to CAP recorded on ClinicalTrials.gov were analysed. Due to high heterogeneity, we divided close CAP inclusion criteria into patterns (i.e. combinations of inclusion criteria). To assess their diagnostic performances, these CAP definition patterns were applied to a reference population of 319 suspected CAP patients, in whom the CAP diagnosis had been confirmed (n = 163) or excluded (n = 156) by an adjudication committee after a systematic thoracic CT-scan and a 28-day follow-up period.

Results: In the 47 RCTs included in the analysis, 42 different CAP inclusion criteria combinations were identified and 8 patterns created. This heterogeneity was not explained either by the trials' methodology or by their objectives. When applied to the reference population, the performance ranges of the 8 definition patterns were 9.8-56.4% for sensitivities, 56.4 97.4% for specificities, 63.6 83.6% for positive predictive values and 50.8-66.7% for negative predictive values. None of the CAP definitions had both sensitivity and specificity superior to 65%. Depending on the CAP definition, the rate of included patients without CAP ("false positives") ranged from 1 to 21%.

Conclusions: CAP diagnostic criteria within RCTs are heterogeneous, which may have far-reaching consequences on validity of RCT results.

Keywords: Clinical trial; Community- acquired pneumonia; Diagnostic criteria; Inclusion criteria; Randomized clinical trial.

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Conflict of interest statement

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

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Figures

**Fig. 2**
Application of the CAP definition patterns to the 319 patients of the ESCAPED database, example of CAP definition pattern 1

See this image and copyright information in PMC

References

1. European Respiratory Society . European lung whitebook. 2013.
1. Wunderink RG, Waterer GW. Clinical practice. Community-acquired pneumonia. N Engl J Med. 2014;370:543–551. doi: 10.1056/NEJMcp1214869. - DOI - PubMed
1. Ruiz-Gonzalez A, Falguera M, Nogues A, Rubio-Caballero M. Is Streptococcus pneumoniae the leading cause of pneumonia of unknown etiology ? A microbiologic study of lung aspirates in consecutive patients with community-acquired pneumonia. Am J Med. 1999;106:385–390. doi: 10.1016/S0002-9343(99)00050-9. - DOI - PubMed
1. Claessens Y-E, Debray M-P, Tubach F, Brun AL, Rammaert B, Hausfater P, et al. Early chest computed tomography scan to assist diagnosis and guide treatment decision for suspected community-acquired pneumonia. Am J Respir Crit Care Med. 2015;192:974–982. doi: 10.1164/rccm.201501-0017OC. - DOI - PubMed
1. Upchurch CP, Grijalva CG, Wunderink RG, Williams DJ, Waterer GW, Anderson EJ, et al. Community-acquired pneumonia visualized on CT scans but not chest radiographs: pathogens, severity, and clinical outcomes. Chest. 2018;153(3):601–610. doi: 10.1016/j.chest.2017.07.035. - DOI - PMC - PubMed

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High heterogeneity in community-acquired pneumonia inclusion criteria: does this impact on the validity of the results of randomized controlled trials?

Collaborators

Affiliations

High heterogeneity in community-acquired pneumonia inclusion criteria: does this impact on the validity of the results of randomized controlled trials?

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Ethics approval and consent to participate

Consent for publication

Competing interests

Publisher’s Note

Figures

References

MeSH terms

LinkOut - more resources

Full Text Sources

Miscellaneous