Ethical dilemma in organ allocation for lung transplantation John-David Aubert Respiratory Division Lausanne-Geneva Lung Tx Centre - Switzerland ERS Vienna 2012

Disclosure - JD Aubert Financial support for travel from: Astellas Boehringer Ingelheim

Organ procurement from deceased donors Why is it different from other therapies ? A treatment strategy with an explicit shortage of organs Unpredictable waiting time from the therapeutic decision (listing) to the effective therapy (transplantation)  anticipation

Donor: 36 yr, death through brain injury, non smoker, PaO2 = 410 mmHg Situation # 1 Recipient 1 63 yr COPD Ex-smoker Intubated in the ICU since 10 days Waiting time : 30 days Recipient 2 35 yr Cystic Fibrosis At home on Oxygen + nutrition by PEG > 6 exacerbations the last year Waiting time : 230 days

Your choice ? Recipient 1 63 yr COPD ? Recipient 2 35 yr Cystic Fibrosis ? 12

Analysis of determinant criteria If you choose 1 the 63 yr COPD: Risk of death for the recipient 1 > Risk for the Recipient 2  Medical efficacy If you choose 2 the 35 yr CF: Younger age Age match with the donor CF is not a self-inflicted disease such as smoke-induced COPD  Equity

Conflicting Principles in Organ Transplantation Medical Efficacy Equity

LET US CHANGE JUST TWO ITEMS….

Donor: 64 yr, death through brain injury, ex smoker, PaO2 = 410 mmHg Situation # 1 bis Recipient 1 63 yr COPD Ex-smoker Intubated in the ICU since 10 days Waiting time : 30 days Recipient 2 35 yr Cystic Fibrosis At home on Oxygen + nutrition by PEG > 6 exacerbations the last year Waiting time : 230 days

Your choice ? (1bis) 1.Transplant the 63 yr COPD 2.Transplant the 35 yr CF 3.Do not accept these lungs

WHO statement (GP 9, May 2010) Organ allocation must be Open Transparent Fair Equitable

Council of Europe: Statute art 15b Organ transplantation should follow the rules: 1.An allocation system should exist 2.Management of the official waiting list 3.Organs should be allocated to officially registered recipients 4.Criteria for registration on the list should be explicit 5.A patient can be registred on only one list 6.Transplant centres should be certified 7.The management of the list and the organ allocation should be controlled at the national level

The ways to allocate organ from deceased donors Random selection Through the economic rules of supply and demand Centre-based through expert opinion of the surgeon By chronological order +/- established exceptions By a severity score of the recipients

The ways to allocate organ from deceased donors Random selection Through the economic rules of supply and demand Centre-based through expert opinion of the surgeon By chronological order +/- established exceptions By a severity score of the recipients

Allocation through the transplant surgeon and/or the transplant pneumologist Pro Decision in expert hands Flexibility in particular cases Optimal match donor- recipient Con Criteria are not open Potential bias Detailed knowledge of each recipient’s history? Cognitive performance 24h a day?

Putative criteria used by the transplant surgeon Priority to the sickest patient Size match between donor and recipient Age difference between donor and recipient > 30 years Extra caution when a TX had turned bad in the previous month!...

 Allocation through the surgeon

Expert surgeon Back to Situation # 1 Donor: 36 yr, death through brain injury, non smoker, PaO2 = 410 mmHg Recipient 1 63 yr COPD Ex-smoker Intubated in the ICU since 10 days Waiting time : 30 days Recipient 2 35 yr Cystic Fibrosis At home on Oxygen + nutrition by PEG > 6 exacerbations the last year Waiting time : 230 days

Chronological order with priorities First come – First served Priority = urgent cases (ICU) IPF, PAH… The allocation is patient-based and no longer centre-based

 Allocation through the surgeon  Centralized patient allocation, with queuing

Donor: 36 yr, death through brain injury, non smoker, PaO2 = 410 mmHg Situation # 2 Recipient 1 53 yr IPF 1st LTX 2007  BOS Listed for redo Under non-invasive ventilation 16/24h Waiting time : 230 days Recipient 2 35 yr Cystic Fibrosis At home on Oxygen + nutrition by PEG > 6 exacerbations the last year Waiting time : 60 days

Your choice ? (2) 1.Re-Transplant the 53 yr recipient 2.Transplant the 35 yr CF 3.Transplant the 35 yr CF and remove the 53 yr recipient from the waiting list

Donor: 36 yr, death through brain injury, non smoker, PaO2 = 410 mmHg Situation # 2 Recipient 1 53 yr IPF 1st LTX 2007  BOS Listed for redo Under non-invasive ventilation 16/24h Waiting time : 230 days Recipient 2 35 yr Cystic Fibrosis At home on Oxygen + nutrition by PEG > 6 exacerbations the last year Waiting time : 60 days

Redo LTX: usual practice Same priority as first LTX Some programs do not consider urgent status for Redo recipients (e.g. France)

LAS Calculator The Lung Allocation Score (LAS) is a numerical calculation used for allocating lungs to candidates who are 12 years of age or older. The LAS is calculated from clinical diagnostic factors which estimate each candidate's waitlist urgency and post-transplant survival probability Lung allocation score LAS - USA

Is it possible to predict, before transplantation, the survival after LTX?

Predictive ROC curve for specific preTX diagnosis DiagnosisCOPDIPFCF AUC AUC = 0.5  Random AUC = 1.0  Perfect prediction

THE LUNG ALLOCATION SCORE IS MORE PREDICTIVE FOR THE WAITING LIST MORTALITY THAN THE POST TX SURVIVAL An understatement…..

 Allocation through the surgeon  Centralized patient allocation, with queuing  Lung allocation severity score

Expert surgeon Centralized allocation + urgency criteria LAS Back to Situation # 1 Donor: 36 yr, death through brain injury, non smoker, PaO2 = 410 mmHg Recipient 1 63 yr COPD Ex-smoker Intubated in the ICU since 10 days Waiting time : 30 days Recipient 2 35 yr Cystic Fibrosis At home on Oxygen + nutrition by PEG > 6 exacerbations the last year Waiting time : 230 days

Donor: 36 yr, death through brain injury, non smoker, PaO2 = 410 mmHg Back to situation # 2 Recipient 1 53 yr IPF 1st LTX 2007  BOS Listed for redo Under non-invasive ventilation 16/24h Waiting time : 230 days Recipient 2 35 yr Cystic Fibrosis At home on Oxygen + nutrition by PEG > 6 exacerbations the last year Waiting time : 60 days LAS= 50.65LAS = 40.20

How to compare different allocation systems ? Number of lung TX/ Mio habitants ? Median waiting time on the list ? Mortality on the waiting list ? Acceptance rate of organs ? Survival 1,3, 5 years after lung TX ?

Would you transplant « Joe the ugly » ? A 49 yr prisoner, with rapidly progressing IPF. Jailed with life- sentence for numerous crimes and murders

Your choice case # 3 1.This prisoner should be put on the waiting list 2.This prisoner should not be offered a lung transplant 3.Unsure

Shocking: Doctors have given new lungs to Joe the Ugly! If you answered yes, Have you thought on the impact on organ donation to this type of recipient in the general population ?

My choice: Do not list Joe the Ugly for lung TX The reason: he did not quit smoking….

To conclude Organ transplantation = therapy with explicit shortage of supply Equity and medical efficacy are the two (sometimes) antagonistic forces that drive the process Different allocation systems coexist within Europe Comparison of distinct allocation systems should not be based on a single parameter