A regulator, policy maker and patient perspective · Better health and wellbeing for all Australians through regulatory excellence • New pathways – earlier access to promising

Opening plenary session – The patient will see you now! A regulator, policy maker and patient perspective

Dr Jane Cook First Assistant Secretary – Medicines Regulation Division Health Products Regulation Group (TGA), Department of Health ARCS Annual Conference

06 AUGUST 2019

Overview

• Background • Technological challenges and the Therapeutic Goods Act • Patient focus -access to new promising therapies • New technologies with challenges for patients and regulators • Involving consumers in regulation and patient reported outcomes • What is patient centred care? • Future role

ARCS Annual Conference - 2019 1

“The patient will see you now” Eric Topol • “bottom-up medicine,” • “digitally empowered” patients

take charge of their own health care.

• smart phones and social media democratise medicine

• massive open online medicine (MOOM)


Problems or not?? • Information asymmetry

• Market failure

• Health literacy – Dr Google

• Security

• Informed choice: – Better understanding of risks and

benefits – Improved compliance and better

outcomes

• Targeted therapies


Role of the Regulator • Ensure therapeutic products (devices, medicines, biologicals,

blood and tissue products) marketed in Australia are safe, of good quality, efficacious or fit for purpose for the public.

• We do this through evaluating data submitted by sponsors (safe and effective/fit for purpose), undertake GMP inspections (quality) and post market monitoring


Challenges – massive technological changes since Therapeutic Goods Act introduced in 1989 - does it remain fit for purpose? It can accommodate:

New clinical trial designs

Biosimilars

Personalised medicine

Self testing, including genetic DTC

Cell and tissue therapies

CART - T cells

Medical apps 3D printing


How we evaluate therapeutic goods is not specified in any detail in the legislation

Therapeutic Goods Act 1989 Section 25 Evaluation of therapeutic goods ….. the Secretary must evaluate the goods for registration having regard to whether the quality, safety and efficacy of the goods for the purposes for which they are to be used have been satisfactorily established


Patient focus? Vision: Better health and wellbeing for all Australians through regulatory excellence

• New pathways – earlier access to promising new therapies • Improved information for consumers and health care professionals:

– Product Information and Consumer Medicine Information reformatting – Information Hubs – Breast implants, urogynaecological mesh, codeine, advertising – Public facing databases – DAEN, PI/CMI (MedSearch app), medicine shortages

• Supported by modification to schemes and then guidance to industry as therapies change:

– Faecal Microbial transplantation – Software as a medical device – 3D printing


New pathways - earlier access • Promising medicines:

– Priority pathway (full dossier) reduced assessment time – Provisional pathway (early data on safety and efficacy, immediate availability

outweighs uncertainty

• Other medicines: – Comparable Overseas Regulator (COR A and B) pathways – Work-sharing – Health Canada, Swiss medic and Singapore

• Role of Patient reported outcomes ARCS Annual Conference - 2019 8

Gene Therapy • Will see increasing number for approval • CRISPR has made gene modification easier,

cheaper and more accurate

• Use genetically modified viral vectors or genetically modified cells

• Tisagenleucel KMYRIAH – lymphoma/leukemia

• Not without some risk: – Cytokine-release Syndrome or Cytokine storm – Permanent or not? – Targets wrong cells – Results in unwanted mutations – Unknown or unintended long term

consequences? ARCS Annual Conference - 2019 9

Faecal Microbial Transplantation • Promising new therapy

• Treatment of Clostridium difficile - good evidence

• Other uses:

– Gastro-intestinal such as Cohn’s Ds and Irritable Bowel

– Non—bowel – obesity, insulin resistance, fatty liver?

– Depression and other psychiatric conditions?

• Do it yourself FMT?


Precision medicine/ personalised medicine • Diagnosing/preventing genetic disease • Cancer diagnosis and treatment • Determining patient suitability for

particular medicines • Chronic multi-genic conditions –

diabetes, heart disease

• Targeted therapies designed after identification of a biomarker associated with the disease/condition

• A companion diagnostic is essential for the safe and effective use of the therapeutic – to identify patients who will respond, and to not inflict the wrong treatment on unresponsive patients

• Requires coordinated commercial development and regulatory review of the therapeutic and diagnostic

• Regulators will need to identify and assess whether tests are true companion diagnostics for targeted therapeutics are needed


Software as a medical device • Smart phone – a powerful computer you carry around

capable of monitoring, diagnosing and treating

• Software easily developed and available in the app store or google play – being downloaded and used in large numbers through “personal importation”

• Uses machine learning and AI – robustness of the algorithms used?

• If a medical device does it meet the essential principles – is it safe, of good quality and fit for its intended use?


Self testing - IVDs • Already some – glucose, pregnancy • Direct-to-Consumer (DTC) advertising on

internet • Not on ARTG • Include:

– infections – influenza, chlamydia, HIV – Genetic testing – curly hair to specific disease

markers – Tests for serious disorders such as heart

attacks and cancer

• Current thought is there needs to be medical supervision


New technologies bring new uncertainties – regulators must adjust risk and safety thresholds for different populations

The intended population is critical … patients consistently will accept more risk than regulators


Consumers and regulation Regulators involve patients in Committees e.g. ACM, ACMD Guidelines used such as: • ICH Harmonized Guideline: Revision of M4E Guideline on

Enhancing the Format and structure of Benefit-Risk Information

• Patient- Focused Drug Development framework • Guidance for Industry (FDA) • Appendix 2 to the guideline on the evaluation of

anticancer medicinal products in man - the use of patient-reported outcome (PRO) measures in oncology studies (EMA)


Patient report outcomes

• Capture patients perspectives, complement other clinical outcome measures

• Ensure the clinical outcomes are relevant valued, preferred by the patient

• Include single and multidimensional measures of symptoms, HRQL, health status, adherence to treatment and satisfaction with treatment

• Outcome measures such as Overall Survival, Progression Free Survival, biomarker measures and adverse events do not capture the impact of treatment on the individual


Do we have the right tools? • Growing area in clinical trial design but becoming standard

practice in CTs • Can measure primary or secondary outcomes in clinical trials

evaluating new medications and treatments • PROMs and PREMs • Personal impact of illness and treatment, including physical

functioning, ability to maintain daily activities, and emotional wellbeing

• Can be general eg HRQoL • Evidence that condition specific PROs are more sensitive to

change following intervention • These measures have also been shown to facilitate patient-

provider communication and share decision-making ARCS Annual Conference - 2019 17

Do we have the right tools? • SPIRIT-PRO: Guidelines for Inclusion of

Patient-Reported Outcomes in Clinical Trial Protocols

• Examples: – Quality of life e.g. EQ-5D, AQoL – Symptoms e.g. pain (NPRS), fatigue (FSS) – Distress e.g. depression (K10, PHQ2), anxiety

(GAD7) – Functional ability e.g. WHODAS 2.0, ODI – Self-reported health status e.g. SF-36 – Self-efficacy e.g. GSE

• Collected by: – Paper – Social media – Website - Smart phone/tablet/computer


Patient-centred care – isn’t this what we want?

Picker Institute and Harvard Medical School

Respect for patients’ preferences

Coordination and integration of care

Information and education

Physical comfort

Emotional support

Involvement of family and friends

Continuity and transition

Access to care

Picker’s Eight Principles of Patient Centred Care 19

Regulators role in patient centred care

• Some of key principles fall outside of the purview of a regulator • The following apply: Respect for patient values, preferences and expressed needs Information and education Access to care

• More than just involvement in drug development, evaluation and benefit risk assessment

• Importance of patient –based evidence.


The future • Consumers have access to information

and products – internet, social media

• Is the role moving to that of needing to provide information that helps consumers make the right decision for them based on scientific data

• Improving health literacy

• Greater consumer collaboration in regulation


22

Thank you

ARCS Annual Conference - 2019

Documents

A regulator, policy maker and patient perspective · Better health and wellbeing for all Australians through regulatory excellence • New pathways – earlier access to promising