EULAR RODS 2013 The payer perspective Garner.pdfEULAR RODS 2013 The payer perspective Sarah Garner, ... imatinib -randomised retrospective cohort study ... Nor is it a claim that the

EULAR RODS 2013

The payer perspective

Sarah Garner, PhD BPharm MRPharm S

Associate Director R&D NICE

[email protected]

NICE decision making

What gets taken into account?

Evaluation

Legislation

•Equality & Diversity

•Human rights

Scientific value

judgements

Social Value Judgements

Uncertainty

Cost-

effectiveness Clinical-

effectiveness

Patient experts

Clinical

experts

Consultation

Comments

What type of uncertainties?

• clinical effectiveness

• cost effectiveness

• implementation

• outcomes

• accuracy of a test

• clinical prediction

rules

• diagnosis

• prognosis

• rates of harms

• patients’ experience

• measurements of outcome

• service delivery

• organisation

• methods

RCTs • May be unnecessary, inappropriate, inadequate, or impractical

• Efficacy versus effectiveness

• Population: may not be available for sub-populations and vulnerable

populations

• Interventions: may not be able to assign high-risk interventions

randomly

• Comparators: may not represent standard care

• Outcomes: may report intermediate outcomes rather than main

health outcomes of interest

• Timing: may be too short in duration

• Setting: may not represent typical practice

• Expense and bureaucracy

Efficacy v effectiveness • Efficacy

– patient benefit and harm in experimental and closely monitored research studies, normally RCTs.

– Design minimises bias- high internal validity

– generalisability questionable • restricted entry criteria

• unrepresentative settings

• Effectiveness

– patient benefit and harm when the technology is actually applied in everyday practice.

• pragmatic clinical trials

• observational studies

• synthesis

Recent appraisals TA 232 Retigabine for the

adjunctive treatment of partial onset seizures in epilepsy.

Clinical trials mandated forced (protocol-driven) titration rather than titration tailored to individual patient as is seen in practice.

TA278 Omalizumab for treating severe persistent allergic asthma (review of TA 133 and 201).

Observational data used for extrapolation of treatment effect and for HRQoL in children amongst other things.

TA279 Vertebral fractures – Vertebroplasty and kyphoplasty

Observational data used by committee to accept mortality benefit (however committee could not use the data to quantify it).

TA283 Ranibizumab for treating visual impairment caused by macular oedema secondary to retinal vein occlusion

Observational data used by committee to assess safety compared with unlicensed bevacizumab, however committee stopped short of using it for cost-effectiveness analysis.

Appraisals using non-RCT data for estimates

of clinical efficacy used in modelling TA 151 Diabetes – Insulin pumps Clinical efficacy from a registry – Insulin Pumps

Clinical database - much larger, of longer duration and

more representative of people likely to be considered

for CSII therapy in routine clinical practice than the

populations in the RCTs available

TA 165 Organ preservation (renal) - machine

perfusion and static storage

Prospective cohort study and multi-national registry

study used for efficacy in model

TA 166 Hearing impairment - cochlear implants Baseline risk of operative mortality in model, other

parameters in modelling as judged most appropriate

source

TA 185 Soft tissue sarcoma – trabectedin Three uncontrolled phase II trials of trabectedin

TA 188 Human growth hormone (somatropin)

for the treatment of growth failure in

children (review)

Kabi International Growth (KIGS) observational

database

TA 202 Chronic lymphocytic leukaemia –

ofatumumab

NO RCT- conditional license

TA 209 Gastrointestinal stromal tumours

(unresectable/metastatic) – imatinib

One non-randomised retrospective cohort study

TA 241 Leukaemia (chronic myeloid) -

dasatinib, nilotinib, imatinib (intolerant,

resistant)

Twelve studies were observational (seven of dasatinib,

four of nilotinib and one retrospective study of both)

three single-arm studies of high-dose imatinib –

available RCTs were of poor quality

Appraisals using non-RCT data for

some parameters in model

TA 167 Abdominal aortic aneurysm

- endovascular stent-grafts Large registries of relevance to

UK practice - baseline risk of

operative mortality in model, other

parameters in modelling as

judged most appropriate source

Appraisals using non-RCT data for

longer term effectiveness

TA 177 Eczema (chronic) – alitretinoin

TA 211 Constipation (women) – prucalopride

TA 221 Thrombocytopenic purpura – romiplostim

TA 247 Rheumatoid arthritis - tocilizumab (rapid review TA198)

TA 293 Thrombocytopenic purpura – eltrombopag (review)

guidance.nice.org.uk/TAG/313

Registries used

• BSRBR

• Early Rheumatoid Arthtis study

• United States National Databank

Uses of registry data

• Non-adherence

• Discontinuation

– Time on first biologic conditional on EULAR response

– Median treatment time 319 days

• Patient weight: dosing /costs

• Average starting age

• Population characteristics

• Risk of withdrawals due to adverse events

HAQ trajectory following initial response:

bDMARDs

18

Mean HAQ by EULAR response category

for those receiving biologic DMARDs

Hierarchies of evidence should be

replaced by accepting—indeed

embracing—a diversity of

approaches.

This is not a plea to abandon RCTs

and replace them with observational

studies. Nor is it a claim that the

bayesian approaches to the design

and analysis of experimental and

non-experimental data should

supplant all other statistical methods.

Rather, it is a plea to investigators to

continue to develop and improve their

methods; to decision makers to avoid

adopting entrenched positions about

the nature of evidence; and for both

to accept that the interpretation of

evidence requires judgment.

Why the reluctance?

• Human nature?

• Statistical jiggery pokery?

• Concerns over confidentiality

• Research or care?

• Ethical issues: coercion

• Terminology

• Methods?

• How to define best practice

– Critical appraisal tools

The world is changing…

• Personalized medicine

• Comparative effectiveness agenda in the US

– PCORI

– Registry of patient registries

• Data linkage initiatives eg UK CPRD

• Electronic Healthcare records and PROMS

• CONSORT statements

• ISPOR and GRACE critical appraisal for non-RCTs

• EMA and Cochrane non-RCT methods working group

• IMI 7th call : GetReal Consortium

Slide 22

Pre-Clin PoC 2a

Dose range P2b

Confirmatory P3 (x2)

integrated ‘Real-world’

P4

Regulatory HTA/Reimb

HEOR (obs) studies Meta-analysis

Modelled effectiveness

HTA/Reimb

review

Regulatory

safety review

P3b (x n) ‘Early RW’

Trials and Obs studies of comparator(s) Trial simulations

?