Role of observational studies
in the UK
D S
Dr
Sarah
hG
Garner BPharm PhD MRPharmS
Associate Director Research& Development
NICE
National Institute for Health and
Clinical Excellence (NICE)
•
•
•
Public health – guidance on the
promotion of good health and the
prevention of ill health for those
working in the NHS
NHS, local authorities
and the wider public and voluntary
sector
Clinical practice – guidance on the
appropriate treatment and care of
people with specific diseases and
conditions within the NHS.
Health technologies – guidance on the
use of new and existing medicines
medicines,
treatments and procedures within the
NHS
Fund
within 3
months
What gets taken into account?
ClinicalClinical
effectiveness
Costeffectiveness
U
Uncertainty
t i t
Scientific value
judgements
Consultation
C
l i
Comments
E l ti
Evaluation
Patient experts
Legislation
Clinical
experts
•Equality & Diversity
•Human rights
Social Value Judgements
Efficacy v effectiveness
• Efficacy
– patient benefit and harm in experimental and closely
monitored research studies, normally RCTs.
– major advantages in minimising bias
– generalisability questionable
• restricted entryy criteria
• unrepresentative settings
• Effectiveness
– patient benefit and harm when the technology is
actually applied in everyday practice.
• pragmatic clinical trials
• adverse event reporting
• clinical audit
• Registries?
Existing UK arrangements
• Routinely collected activity data in the NHS
– inadequate information about benefits or adverse events.
– current coding
g methods inadequate for new procedures
– outcome data might not be suitable.
• Existing databases
– Some DH funded e.g. Central Cardiac Audit Database.
– Professionally organized
• Survive in isolation
• Uncertain future funding e.g. vascular databases for aortic
and carotid stenting
– smaller databases
• Enthusiasts
• Little support
• Not
N t comprehensive
h
i ,
The Interventional Procedures
Programme
• guidance on large numbers of
procedures.
• many relatively new - evidence
base limited.
• its guidance frequently specifies
the need for further data
collection.
• submission to well established
registers is recommended when
these are available, but often
they do not exist
Why data collection is needed
•
•
•
•
Facilitate introd
introduction
ction of ne
new proced
procedures.
res
Clinical governance – both locally and nationally.
T
Target
t areas off uncertainty.
t i t
Comprehensive data collection if submission is a
requirement
i
t ffor using
i th
the procedure.
d
• Accrue data which will help to resolve
uncertainties.
uncertainties
• Produce data to inform production and review of
guidance.
guidance
What’s
What
s happened so far?
• Recommending submission to well established
existing registers.
– But ownership/retrieval
p
of data?
• Facilitating the establishment of new (external)
registers
– This has proved time consuming and complex.
• Producing audit tools through the Institute’s
arrangements with CASPE.
– not been designed for collection of data on a national
scale.
• Programme Objective
– Does anti-TNFαtherapy
anti TNFαtherapy in patients with
rheumatoid arthritis (RA) increases the risk of
malignancy, important co-morbidity
co morbidity and
severe infection?
– How are these risks characterized?
• any relationship to dosage or duration of therapy?
any
y spec
specific
cd
disease
sease ccharacteristics
a acte st cs that
t at act
•a
synergistically toincrease the risk?
• do multiple biological agents act synergistically to
i
increase
th
the risk?
i k?
– Using normal clinical indicators, what are the
risk/ benefit ratios for adverse outcomes?
Ad li
Adalimumab
b
Abb t
Abbot
4000
Etanercept
Wyeth
4000
Infliximab
Scheringplough
Amgen
4000
Anakinra
DMARD
control
2500
3900
Recruitment and follow-up
BSRBR
6 Monthly
Consultant
questionnaire
Annually
5 YEARS
6 Monthly
Patient
questionnaire
& diary
3 YEARS
Office for National
Statistics (ONS)
flagging
Year 0
LIFE LONG
Year 3
Year 5
Incidence
e rate rratio (9
95% CII)
5.0
Follow-up period of risk estimate
4.0
UK national register
US claims data
3.0
RCT meta-analysis
Swedish national register
German national register
2.0
10
1.0
0.8
1
2
3
Ti
Time
period
i d off risk
i k assessmentt (years)
(
)
0.6
Slide courtesy of Will Dixon
BSR and NICE Appraisals:
• Multiple Technology
Appraisals(MTA)
• Adalimumab, etanercept
and infliximab for
Ankylosing Spondylitis
• Adalimumab, etanercept
and infliximab for
Rheumatoid Arthritis
• Etanercept and infliximab
for Juvenile Idiopathic
Arthritis
Single Technology Appraisals
(STA)
• Adalimumab for Psoriatic
Arthritis
• Leflunomide
e u o de for
o Psoriatic
so at c
Arthritis
• Rituximab for Rheumatoid
Arthritis
• Abatacept for Rheumatoid
A th iti
Arthritis
IN
OUT
“Good work ……. but I think we need
just a little more detail right here”