Professional Standards for Innovation Wendy Rogers Professor of Clinical Ethics, Macquarie University ESRC Seminar Series Liability v Innovation QUT, 22 Feb 2017

An heroic tale Paolo Macchiarini: superstar surgeon First synthetic trachea implanted in 2009 in Sweden Tailored bioartificial nanocomposite Seeded with autologous bone-marrow mononuclear cells Matured for 36 hours in a ‘bioreactor’ prior to implantation

Outline The gaps in evaluating surgical innovation The IDEAL framework Bringing ethics into the picture De facto regulation?

1. Evaluating surgical innovations “Evaluation of a therapeutic, procedure-based intervention presents several methodological and practical challenges for the surgical research community.” (Ergina et al 2009) Challenges Study design: RCTs vs non-RCTs Nature of surgical interventions: complexity, surgeon- related, multiple outcomes Master-apprentice model of surgery Nature of surgical careers Lack of funding Lack of regulation of surgical techniques/instruments

Is it research? National Statement on Ethical Conduct in Human Research (NHMRC 2007) “Whether a change in an individual’s investigation or treatment is simply an innovation or actually constitutes clinical research is generally a matter for the responsible clinician’s judgement, guided by institutional policies. Systematic evaluation of an innovation is research and requires ethical review.”

NS current section 3 revision Glossary entry: Innovation: In the research context, an innovation involves the introduction of one or more novel elements of an intervention that represent/s a substantive departure from the spectrum of standard care or service delivery. An innovation may apply modalities or strategies used and tested in one domain to a novel application. An innovation may or may not be therapeutic in intent or effect and may or may not be considered to be experimental; however, a condition of research involving an innovation is that the safety, efficacy, or effectiveness of the innovation in the context in which it is used is not known at the onset of the research.

2. The IDEAL Framework Barkun et al 2009

A cautionary tale 7/9 patients died 2 artificial tracheas removed 2 investigations and a documentary: Failure to obtain ethics approval or consent Falsification of published data Macchiarini disgraced Karolinska Institute senior staff and ethics council dismissed

3 Bringing ethics into IDEAL Stage 0: Preclinical Basic science Animal studies Bench testing/simulations Ethical issues Animal welfare and validity of animal studies Problematic assumptions in bench testing/simulations Conflicts of interest General standards of research integrity

Stage 1: Proof of concept Research method: Structured case reports First in human studies with unstable and evolving intervention Ethical issue Strategy Failure to identify innovation Use formal tools/mechanisms to identify when incremental innovation occurs Minimise harm Provide oversight to review potential and actual harms as cases proceed Patient consent Use innovation specific consent processes Team communication Use team briefings for innovative procedures Conflicts of interest Use review by oversight committee/person Justice issues Establish stage 1 registers; report of all results; ensure care for patients with obsolete innovations

Stage 2a: Development Research method: Prospective development study/single centre case series Iterative modification of intervention seeking stability, with data collected on all modifications Research ethics framework applicable, but may be avoided if research described as ‘audit’ Major issues: Minimising harm: surgical skills training Detailed patient consent Publishing outcomes (cf intellectual property) Oversight

Stage 2b: Exploration Research method: research data base, exploratory RCT Innovation stabilised and described, now taken up beyond home institute Research ethics framework applicable Major issues: Minimising harm: learning curve Fair patient selection Standardisation of patient consent Patient reported outcomes Publication of results

Stage 3: Assessment Research method: RCTs Testing of stable innovation at multiple sites for efficacy Research ethics framework applicable Major issues: Generation of valid data Fair inclusion and exclusion criteria Equity in research participation Patient relevant outcomes Surgeon training/learning curve Publishing outcomes

Stage 4: Long term Research method: registries, databases Community ‘roll out’ of stable innovation with known safety and efficacy No research ethics framework: ethics of clinical care cf big data/linked data initiatives (learning healthcare systems) Major issues: Equity in access and uptake Collection of effectiveness data with action thresholds Combatting technological misconception Conflicts of interest

Discussion: de facto regulation? What is the status of papers put out by groups claiming leadership in an area, such as the IDEAL group? What is the potential regulatory role of these kind of documents? cf other measures: Professional duty to register research Journal requirement for registration

Thank you Thanks also to Katrina Hutchison and to members of the ARC Linkage grant team and Partner Organisations Disclaimer: co-author on the current IDEAL update paper and lead author on the IDEAL ethics paper