Approaches and processes for paediatric chest X-ray classification used in the SHINE TB treatment-shortening trial

Abstract

<sec><title>INTRODUCTION</title>SHINE (Shorter Treatment for Minimal Tuberculosis in Children) was the first Phase 3 paediatric TB treatment-shortening trial. Robust chest X-ray (CXR) classification methods were integral to excluding severe disease for trial eligibility and to retrospectively adjudicating TB status at baseline. We describe and critically evaluate the CXR classification approaches and processes used in the SHINE trial.</sec><sec><title>METHODS</title>Children with non-severe TB were randomised to 4- vs 6-months anti-TB treatment. Radiologically non-severe TB was defined on CXR. CXRs were systematically interpreted by on-site clinicians prospectively for eligibility determination and retrospectively by experts to inform adjudication of baseline TB status and disease severity.</sec><sec><title>RESULTS</title>A screening CXR was successfully obtained from all 1,204 enrolled children; 1,134 CXRs from children with intra-thoracic TB were reviewed by expert readers. Compared with the expert panel, enrolling clinicians classified more CXRs as abnormal and 'typical TB' and all as radiologically non-severe. The expert panel retrospectively classified 71/1,134 (6%) CXRs as severe. Of these, 4 (5.6%) had unfavourable outcomes compared with 34 (3.0%) in the trial overall.</sec><sec><title>DISCUSSION</title>Using CXRs to classify radiological disease severity and inform eligibility decisions in real-time by local enrolling clinicians was feasible and safe in this large paediatric TB trial. Retrospective central expert CXR review was successful. Refinement of the CXR methods for the classification of both disease severity and TB status could support standardised implementation in routine care and research.</sec>.

Figure 1. Schematic illustration of the process used by on-site clinicians and expert readers to classify each individual chest x-ray according to radiological pattern in the SHINE trial

Schematic illustration of the process used by on-site clinicians and expert readers to classify each chest X-ray by radiological pattern in the SHINE trial. *Lymph node enlargement with bilateral airway compression or associated with unilateral hyperinflation or collapse or ≥1 lobe opacification (consolidation). ^†Pleural effusion with pneumothorax or loculated or with underlying opacification (consolidation). ^‡Bronchopneumonic consolidation with cavities and presence of enlarged lymph nodes. ^§Included multi-lobar pneumonia. SHINE = Shorter Treatment for Minimal Tuberculosis in Children.

Figure 2. Flow of screening chest x-ray images and chest x-ray data between trial sites, central Medical Research Council Clinical Trials Unit and the Desmond Tutu TB Centre for expert central review

Flow of screening CXR images and CXR data between trial sites, MRC CTU and the DTTC expert central review. CXR = chest X-ray; ERC = Expert Review Committee; MRC CTU = Medical Research Council Clinical Trials Unit; DTTC = Desmond Tutu TB Centre; SOE = schedule of evaluations; SHINE = Shorter Treatment for Minimal Tuberculosis in Children.

Figure 3. Process used to establish the final classification of screening chest x-rays from enrolled children after review by the expert reading panel

FINAL CXR classification after expert review. Process used to establish consensus among expert readers on the classification of screening chest X-rays from children enrolled in the SHINE trial. SHINE = Shorter Treatment for Minimal Tuberculosis in Children; CXR = chest X-ray; R1 = expert reader who interpreted the first CXR; R2 = expert reader who interpreted the second CXR; R3 = expert reader who interpreted the third CXR; *’Diagnostic certainty’ was defined as normal (included cases where one reader classified the CXR as normal and one reader noted the presence of perihilar infiltrates/generalised hyperinflation only) OR abnormal ‘typical TB’ (see Figure 1 for definition) OR abnormal ‘not typical TB’ (defined in Figure 1). ^†’Disease severity’, defined as radiologically severe OR non-severe (see Figure 1 for definition).