EULAR RODS 2013
The payer perspective
Sarah Garner, PhD BPharm MRPharm S
Associate Director R&D NICE
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
?
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