Current diagnostic recommendations for ILD: The multidisciplinary meeting TSANZSRS ASM

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1 Medicine, Nursing and Health Sciences Current diagnostic recommendations for ILD: The multidisciplinary meeting Dr Ian Glaspole Central and Eastern Clinical School, Alfred Hospital and Monash University Disclosures Consultancy fees from Astra-Zeneca, Boehringer-Ingelheim, Intermune Unrestricted educational grant from Boehringer-Ingelheim Current diagnostic recommendations for ILD: The multidisciplinary meeting TSANZSRS ASM

2 Recommendation: We recommend that a multi-disciplinary discussion should be used in the evaluation of IPF (strong recommendation, lowquality evidence). Current diagnostic recommendations for ILD: The multidisciplinary meeting TSANZSRS ASM Current guidelines for diagnosis The process of achieving a multidisciplinary diagnosis in a patient [via] dynamic, close communication between clinician, radiologist, and when appropriate, pathologist Integrated presentation of: Clinical data: presentation, exposures, smoking status, associated diseases, lung function, laboratory findings Radiologic findings Lung biopsy: where more informative than HRCT Key benefits: Improved interobserver agreement in diagnosis Recognising rarer IIP s Clarification of difficult to classify or unclassifiable disease Travis W. Am J Respir Crit Care Med 2013;188: Raghu G. Am J Respir Crit Care Med 2011;188: Current diagnostic recommendations for ILD: The multidisciplinary meeting TSANZSRS ASM

3 In all cases, a multidisciplinary discussion involving pulmonologists, radiologists, and pathologists should be used to establish a confident diagnosis. Behr J. Clin Chest Med. 2012;33:1-10. Current diagnostic recommendations for ILD: The multidisciplinary meeting TSANZSRS ASM What other roles can an MDM perform? Roles Diagnosis Predicting disease behaviour Predicting response to therapy Concensus discussion of management Travis W. Am J Respir Crit Care Med 2013;188: Current diagnostic recommendations for ILD: The multidisciplinary meeting TSANZSRS ASM

4 Assessing the performance of multidisciplinary meetings Current diagnostic recommendations for ILD: The multidisciplinary meeting TSANZSRS ASM ILD MDM s are focused on diagnosis Data Clinical findings Serology Physiology Pathology MDM Diagnosis Current diagnostic recommendations for ILD: The multidisciplinary meeting TSANZSRS ASM

5 Assessing the performance of a diagnostic test: the linked evidence approach Accuracy: Validated against a gold standard Precision: Reproducibility of findings MSAC. Guidelines for the assessment of diagnostic technologies. Canberra, ACT: Commonwealth of Australia; August Current diagnostic recommendations for ILD: The multidisciplinary meeting TSANZSRS ASM Effectiveness of a test the effectiveness of a test depends on: whether the overall accuracy of testing is improved by including the index test (as a replacement or additional test), its impact on therapeutic decisions, the effectiveness of the therapies selected. MSAC. Guidelines for the assessment of diagnostic technologies. Canberra, ACT: Commonwealth of Australia; August Current diagnostic recommendations for ILD: The multidisciplinary meeting TSANZSRS ASM

6 A range of therapeutic choices now exist in ILD Clinical behaviour Example Treatment goal Treatment choices Reversible, selflimited Reversible with risk of progression Stable with residual disease Progressive, irreversible with potential for stabilisation Progressive irreversible disease despite therapy RB-ILD cellular NSIP, some fibrotic NSIP, DIP, COP Some fibrotic NSIP Some fibrotic NSIP IPF Remove possible cause Achieve response, then rationalise longer term therapy Maintain status Stabilise Slow progression Anti-fibrotic therapy, Immune suppression, Lung transplantation, Palliative therapy Other Current diagnostic recommendations for ILD: The multidisciplinary meeting TSANZSRS ASM Primary Efficacy Analysis: Proportion of Patients with %FVC Decline 10% or Death 35 Pirfenidone (N = 278) 30 Placebo (N = 277) 25 Proportion (%) of Patients with 10% FVC Decline or Death Week Relative Difference 54.0%** 58.0%** 57.8%** 47.9%* Rank ANCOVA p value < < <

7 Apr-08 Oct-08 Apr-09 Oct-09 Apr-10 Oct-10 Apr-11 Oct-11 Apr-12 Oct-12 Apr-13 8/04/2015 ANNUAL RATE OF DECLINE IN FVC INPULSIS -1 INPULSIS ml/year (95% CI: 77.7, 172.8) p< Nintedanib 150 mg bid (n=309) Placebo (n=204) 93.7 ml/year (95% CI: 44.8, 142.7) p= Nintedanib 150 mg bid (n=329) Placebo (n=219) Treated set (observed cases); data are adjusted rate (SEM). bid, twice daily; CI, confidence interval; FVC, forced vital capacity. Richeldi L, et al. N Engl J Med 2014; published online May 18, Immunosuppression in PM/DM-ILD Progress: Methylprednisolone 1 gm x 3 days Prednisolone 60 mg daily, with slow wean MTX 20 mg with disease flare Progress: steady and sustained improvement with 1-2 mild disease flares months weeks post presentation Lung function tests 6 weeks and therapy post presentation DATE Prednisolone/10 MTX/10 FEV1 FVC DLCO/10 VA 7

8 Survival (%) 8/04/2015 IPF adult bilateral/double lung transplant Kaplan Meier plot: transplant survival: January 1990 June 2012) (N = 254) (N = 757) /2012 (N = 3,293) 60 N at risk = N at risk = vs : p = vs /2012: p < N at risk = vs /2012: p = Years 2014 JHLT Oct; 33(10): Accurate diagnosis has never been more important in ILD Clear distinction in therapies now exists: Anti-fibrotic therapies for IPF Immuno-modulatory therapies for CTD-ILD, etc Lung transplantation RDBPC trials confirm efficacy of anti-fibrotic therapies in IPF Case series data for MMF, rituximab in CTD-ILD Lung transplantation for ILD produces long term survival and QoL in majority of recipients Current diagnostic recommendations for ILD: The multidisciplinary meeting TSANZSRS ASM

9 Evaluating the multidisciplinary meeting Current diagnostic recommendations for ILD: The multidisciplinary meeting TSANZSRS ASM Accuracy the ability of a test to actually measure what it claims to measure, and is defined as the proportion of all test results (both positive and negative) that are correct Difficult to measure there is no alternative gold standard! Current diagnostic recommendations for ILD: The multidisciplinary meeting TSANZSRS ASM

10 Precision the ability of a test to reproduce the same result when repeated on the same patient or sample Approximately analogous to inter-observer agreement: when provided with the same data, the degree to which observers provide the same diagnosis Current diagnostic recommendations for ILD: The multidisciplinary meeting TSANZSRS ASM Rating observer agreement: the kappa value -1 to 1 <0.20: poor : fair : moderate : good >0.80 excellent Landis J. 1977;33: Current diagnostic recommendations for ILD: The multidisciplinary meeting TSANZSRS ASM

11 Observer agreement among pathologists 10 members of the UK Interstitial Lung Disease panel, provide one of 15 diagnoses for 98 biopsy specimens Agreement of diagnosis was only fair ( = 0.38), Better for patterns with relatively specific histological parameters Eg UIP ( = 0.42), OP ( = 0.57) and sarcoidosis ( = 0.76) Worse for patterns in which multiple features are required or diagnoses of exclusion eg EAA ( = 0.36), NSIP ( = 0.29). Observer agreement was higher in biopsy specimens for which diagnostic confidence was high ( = 0.50) than in those for which diagnostic confidence was low ( = 0.22) Disagreement most often centred upon a diagnosis of NSIP (made in over 50% of cases with divergent diagnoses), particularly discrimination between NSIP and UIP and between end stage lung disease and both UIP and NSIP Nicholson A. Thorax 2004;59: Current diagnostic recommendations for ILD: The multidisciplinary meeting TSANZSRS ASM Observer agreement among radiologists 11 radiologists, HRCT in 131 patients; 65 from tertiary referral centre, 66 from regional centres; free to diagnose any disease entity that they considered classifiable as a diffuse lung disease Moderate agreement ( = 0.48) on the first choice diagnosis for the entire cohort. Observer agreement was substantially higher in unselected consecutive cases from regional teaching centres ( = 0.60) than in biopsied tertiary referral cases ( = 0.34). Agreement substantially higher in cases diagnosed with high confidence ( = 0.68) versus those with low confidence ( = 0.28). Aziz Z. Thorax 2004;59: Current diagnostic recommendations for ILD: The multidisciplinary meeting TSANZSRS ASM

12 Observer agreement improves with MDM Patients with suspected idiopathic interstitial pneumonia referred by participants in the University of Michigan Fibrotic Lung Disease Network Clinical information including symptoms, environmental exposures, comorbid illnesses, medication use, smoking history, family history, physical examination findings, serologic data and pulmonary function data (spirometry, lung volumes, and diffusion capacity for carbon monoxide) Stepwise increase in information and communication: step HRCT Clinical data SLB Clinician Radiologist Pathologist Diagnostic method 1 Solo 2 Solo 3 MDM 4 Solo 5 MDM Current diagnostic recommendations for ILD: The multidisciplinary meeting TSANZSRS ASM Flaherty K. Am J Respir Crit Care Med 2004 ;170: Observer agreement improves with MDM Agreement among clinicians and between clinicians and radiologists was fair-moderate with limited data (step 2, = 0.41 for clinicians) but improves substantially with consensus discussion (step 3: = 0.67, step 5: = 0.86) Agreement between diagnoses provided at consensus clinicalradiological diagnosis (step 3) and the initial pathological diagnosis was only slight for radiologists ( = ) and only fair for clinicians ( = ) but increased substantially following MDM discussion ( = 0.78 to 0.92) When pathology results were provided to the group radiologists were likely to alter their interpretation ( = 0.2 and 0.32 between steps 3 and 4); particularly from NSIP to another diagnosis Total agreement (3 clinicians, 2 radiologists, and 2 pathologists) on a final diagnosis was reached in 47 (81%) of the cases Flaherty K. Am J Respir Crit Care Med 2004 ;170: Current diagnostic recommendations for ILD: The multidisciplinary meeting TSANZSRS ASM

13 Observer agreement improves with expertise Case information provided to 2 community groups, and 1 academic group Academic physicians displayed better agreement compared with community physicians: step 5 final diagnosis ( = 0.71), as compared with the community clinicians ( = 0.44). Major differences between academic and community groups in final diagnoses: clinicians : = 0.20 to radiologists: = pathologists: = Community-based physicians were more likely to make a diagnosis of IPF particularly for IPF vs CHP, IPF vs NSIP and IPF vs CTDILD: academics assigned alternative diagnoses of CHP, NSIP or CTDILD Total extra IPF diagnoses by community clinicians in 11/39 cases Flaherty K. Am J Respir Crit Care Med 2007 ;175: , Current diagnostic recommendations for ILD: The multidisciplinary meeting TSANZSRS ASM Multidisciplinary meeting constitution Current diagnostic recommendations for ILD: The multidisciplinary meeting TSANZSRS ASM

14 MDM a multi-step diagnostic process Clinical data Laboratory findings HRCT Histology Discussion Diagnosis Multiple components Potential for bias based on expertise of attendees, quantity of input, quality and quantity of data provided, discussion format Current diagnostic recommendations for ILD: The multidisciplinary meeting TSANZSRS ASM The effect of MDM constitution Central review panels display different diagnostic performance to individual physicians Thomeer 2008: Patients in IFIGENIA study Local physician diagnosed IPF Central panel review: histologists and radiologists 12.8% diagnosis rejected (using ATS 2000 criteria) Australian IPF registry central review panel 22% of referred subjects display features inconsistent with IPF at centralised review No comparative study of the effect of differing MDM constitution and governance on diagnostic outputs Thomeer M. Eur Respir J 2008; 31: Current diagnostic recommendations for ILD: The multidisciplinary meeting TSANZSRS ASM

15 MDM constitution and governance No guideline currently exists regarding constitution or governance of a multi-disciplinary meeting in ILD Aim: to determine the constitution or governance of ILD multidisciplinary meetings in expert centres around the world Method: Alfred Hospital ethics committee approved SurveyMonkey questionnaire, sent to twelve expert centres in Australia, Europe and USA Results: Responses received from 10/12 centres Current diagnostic recommendations for ILD: The multidisciplinary meeting TSANZSRS ASM Results Organisation and structure All 10 host ILD exclusive MDM meetings MDM usual features (median) frequency of meeting every 1-2 weeks caseload 6 cases duration minutes attendee number 12 Current diagnostic recommendations for ILD: The multidisciplinary meeting TSANZSRS ASM

16 Who attends an MDM Current diagnostic recommendations for ILD: The multidisciplinary meeting TSANZSRS ASM Utility of attendees: frequency of contribution Current diagnostic recommendations for ILD: The multidisciplinary meeting TSANZSRS ASM

17 Chest x-ray High resolution CT chest Pulmonary function tests Six minute walk test findings Cardiopulmonary exercise test Polysomnography Surgical lung biopsy (if available) Transbronchial biopsy (if available) Broncho-alveolar lavage findings Rheumatologic serology Biochemistry Haematology Echocardiography Right heart catheter study 8/04/2015 Marked heterogeneity in governance Wide range of clinical information presentation methods: Current diagnostic recommendations for ILD: The multidisciplinary meeting TSANZSRS ASM Minimum requisite investigations Which investigations are presented as a minimum routine requirement at all case presentations? 120.0% 100.0% 80.0% 60.0% 40.0% 20.0% 0.0% Current diagnostic recommendations for ILD: The multidisciplinary meeting TSANZSRS ASM

18 Clinicians have the dominant role in MDM Who has the greatest influence on diagnosis? % respondents Clinicians lead discussion 100 The responsible clinician documents diagnosis (or their fellow/registrar) 70 The responsible clinician has greatest say in diagnosis formulation 60 Clinicians are the accountable craft group after diagnosis formulation 70 Current diagnostic recommendations for ILD: The multidisciplinary meeting TSANZSRS ASM A range of approaches are taken to diagnostic dilemmas Decision making process in diagnostic dilemmas % respondents Concensus discussion 60 Responsible clinician's decision Open diagnosis with grading of likelihood 10 Suggest further testing 10 Current diagnostic recommendations for ILD: The multidisciplinary meeting TSANZSRS ASM

19 Information generated All provide a diagnosis and 1-3 differential diagnoses 80% respondents include a degree of diagnostic confidence Other information: 80% provide management recommendations 60% provide treatment aims (with regards the best anticipated response to specific therapy) 30% provide a prediction of disease behaviour 20% consider clinical trial entry Current diagnostic recommendations for ILD: The multidisciplinary meeting TSANZSRS ASM How should we best use the MDM Not always necessary, useful or practical Eg, obvious diagnoses, those not requiring therapeutic decision Likely best used for: Majority of ILD diagnoses Particularly: Where differential diagnoses are > 1 Where expected disease behaviour is progressive/fatal Potential need for toxic, expensive and prolonged therapies Outputs if multiple, increase utility Current diagnostic recommendations for ILD: The multidisciplinary meeting TSANZSRS ASM

20 Consider what we don t know Interobserver agreement using most recent diagnostic guidelines Interobserver agreement with regards other MDM outputs (eg disease behaviour prediction) Impact of new diagnostic techniques such as cryobiopsy How to best make telehealth work? Does heterogeneity in MDM constitution and governance matter? How can we minimise biased input/output? How do referring physicians perceive the utility of MDM? What are the reasons MDM s are not utilised? How do clinicians apply the findings of MDM to clinical practice? Current diagnostic recommendations for ILD: The multidisciplinary meeting TSANZSRS ASM