Dr Simon Thomson
Consultant in pain medicine
Basildon and Thurrock University Trust
President of INS

Honoraria and expenses

Codman

Pfizer

ECMT

The primary aim of therapy is to maximise the patients quality of life by ameliorating the effects of the condition without jeopardising quantity of life.

Daily Mail 27 th September 2010
Me and My Operation: The Remote control that switches off Angina Pain

Evidence of clinical efficacy of SCS in angina
Mechanisms of action from animal and human data
Patient population with angina who have unmet need
Limited understanding amongst referrers

Reluctance to refer outside cardiology/CTS
Definition of RA not widely known
Missing elements of evidence base
Poorly developed care pathway
Multiple treatment options
Fears

Safety

Palliative versus prognostic benefits of revascularisation

New patient to angina clinic
Rehabilitation & Optimise risk factors & medication
ANGIOGRAPHY if indicated
Prognostic disease
LMS, Proximal 3VD, or Proximal
2VD that includes LAD
Non-prognostic disease
SVD, 2VD not including prox LAD, distal disease, post revascularisation
Ensure that the patient has received rehabilitation, understands his condition, is on optimal medication and still wants Rx
CABG
If new symptoms develop and angiography shows new prognostic disease
Select from:
TENS
SGB
Opioids
EECP
SCS
PTCA
CABG
Laser etc, etc, etc

Spinal cord stimulation is recommended as a treatment option for adults with chronic pain of neuropathic origin who:
 continue to experience chronic pain (measuring at least 50 mm on a 0 –100 mm visual analogue scale) for at least 6 months despite appropriate conventional medical management, and
 who have had a successful trial of stimulation as part of the assessment specified in recommendation 1.3
Spinal cord stimulation is not recommended as a treatment option for adults with chronic pain of ischaemic origin except in the context of research as part of a clinical trial . Such research should be designed to generate robust evidence about the benefits of spinal cord stimulation (including pain relief, functional outcomes and quality of life) compared with standard care
.

NSUKI research group
National effectiveness study

Collaborative - include cardiology
Public funded SCS project

NIHR
Pilot study

RfPB
Programme grant

National


 Efficacy

 explanatory trials highly selected populations

 comparator: often placebo
A vs B outcomes: clinical, often surrogates, adverse effects
‘is the therapy effective’
 Effectiveness
 pragmatic trials
 few exclusions



 comparator: ‘current (best) practice’
Therapy added to best practice and compared to best practice alone
A+B vs B outcomes: patient-focused, down-stream resources


‘real world added value’
Taylor R.S. Value in Health 2001;4:8-11

Basic biomedical research
Safety & efficacy
Effectiveness and cost-effectiveness
General clinical use
Phase I studies Phase II/III trials Phase IV trials
Licensing Reimbursement

(QALYs)
 Cost per QALY used increasingly by central decision making bodies
 Utility reflects an individual’s preference for a particular state of well being derived from the consumption of healthcare
 Approaches to deriving utility values includes

Preference Based (i.e.,VAS)

Widely used scales include the EQ-5D and the SF-36
 Respondents place their current health status on an anchored interval scale (0-1) from perfect health (1=perfect health) to death with 0=death

Incremental cost effectiveness ratio (ICER)
ICER =
Cost [new technology – current care]
Outcome [new technology – current care] i.e. additional cost per unit of health care gain

Cost
Difference
Max CE
Ratio ( Rc )
DOMINANT
DON’T FUND c
Effect Difference
DOMINANT
FUND

Probability of
Rejection
Inflexion B
£ 25,000 £35,000
Inflexion A
£5,000 - £15,000
Increasing (log) incremental cost-effectiveness ratio

``

Author
(year)
Patient
N
De Jongste
(1994)
22
Rx
SCS
DiPede
(2001)
EBSY
(1998)
30
104
Hauvast
(1998)
Jessurum
(1999)
SpiRiT
(2006)
Eddicks
(2007)
25
24
68
24
Control Primary outcome
Follow up
Quality
No SCS Exercise capacity
2-mths 2/5
SCS ON
SCS
SCS ON
SCS ON
SCS
SCS ON
SCS OFF Ischaemic burden
CABG Exercise capacity.
Angina symptoms
SCS OFF Exercise capacity
SCS OFF Exercise capacity
PMR Exercise capacity
SCS OFF Exercise capacity
48-hrs
6-mths, 2yrs, 5-yrs
2/5
1.5-mths 2/5
1-mth
3, 6, 12,
14-mths
1-mth
3/5
2/5
4/5
4/5

SCS outcomes were similar when compared to CABG or PMR
SCS versus “No Stim”

Improvements in all outcomes

Significant gains in exercise capacity
Decreased healthcare costs at 2 years vs
CABG

Spirit trial

Better outcomes for QoL and survival in second half of recruitment

ICER not favourable
ESBY

Not Refractory angina

SCS as good as comparator for pain but not ischaemic burden

ICER not favourable

Costs were comparative

Costs
QALYs
ICER
Cost per QALY @ 2-yr
SCS
(n=34)
Percutaneous myocardial laser revascularisation
(n=34)
£17,736 £12,215
Difference
+£5,520
1.19
1.07
+0.12
£46,000 per QALY
Dyer (2008) BMC Trials [on line]

For patients recruited during 2000/01, the ICER was estimated at £230,000 per QALY (95% CI: -
£267,000 to £590,000)
For 2002/03, the ICER was estimated at
£18,000 per QALY (95% CI: -£21,000 to 51,000)
This improvement can largely be explained by better outcomes, in terms of survival and QoL, experienced by SCS patients in the second half of the study
Dyer (2008) BMC Trials [on line]

SCS appears to be an effective and safe treatment option in the management of refractory angina patients and of similar efficacy and safety to PMR, a potential alternative treatment. Further high quality
RCT and cost effectiveness evidence is needed before SCS can be accepted as a routine treatment for refractory angina.

December 20th 2008 Hilton Paddington
Invited meeting 25 invitations
19 attendees




4 Cardiologists
8 Anaesthetists
1 Academic health service researcher
7 Industry representatives

(PB-PG-1208-18031)
Investigators

CI: Sam Eldabe (Middlesborough)

Local PIs: Simon Thomson (Basildon), Jon
Raphael (Dudley)

Cardiologists: Mark deBelder (M/brough),
Rajesh Aggarwal (Basildon)

Health economist: Andrea Manca (York)

Statistician: Rod Taylor (Exeter)

(PB-PG-1208-18031)


Part 1 – UK Survey current management of RA patients the number of RA patients treated in the last 12-months and details of their medical treatment
 views of medical staff on the suitability of SCS as a treatment option for RA
 willingness to participate in a multicentre trial of SCS
Part 2 – Pilot trial (RASCAL)

R efractory
A ngina

S pinal
C ord stimulation usu
AL care

To assess recruitment, uptake and retention of subjects in both groups
To assess the feasibility and acceptability of SCS treatment from the point of view of patients and referring physicians
To assess the feasibility and acceptability of standardising usual care from the point of view of patients and referring physicians

To test the feasibility and acceptability of the proposed trial outcome measures in both groups
Results from this pilot study will inform the design and power for a defintive multicentre RCT

Refractory angina pectoris is a chronic condition characterized by the presence of angina caused by coronary insufficiency in the presence of coronary artery disease which cannot be controlled by a combination of medical therapy, angioplasty and coronary bypass surgery. The presence of reversible myocardial ischaemia should be clinically established to be the cause of the symptoms. Chronic is defined as a duration of more than 3 months

Report from the European Society of Cardiology Joint Study
Group on the Treatment of Refractory Angina
European Heart Journal (2002) 23, 355 –370

More pragmatic and practical definition for clinical use
Delay in diagnosis of RA prevented
Patient centred decision making
Chronic stable angina that persists despite optimal medication and when revascularisation is unfeasible or where the risks are unjustified


Chester MG, et al http://www.angina.org/?page_id=18 Accessed July 2010

Prevalence in UK

Estimated 50,000 to78,000 by 2020
Incidence


10,000 new cases per year
£2.5 billion on revascularisation over 10 years
£1 billion of this spent on palliative procedures

RA as defined by one cardiologist and either cardiologist or CTS
Other pain causes excluded by Pain physician
Inclusion





Limiting angina CCS 3+ on optimal medical treatment
Angiographically documented CAD
Not suitable for revascularisation in opinion of referring
Satisfactory multidimensional pain assessment
Demonstrable ischaemia on functional testing

Exclusions

Presence of pacemaker or implanted defibrillator that is incompatible with SCS

Patient refusal to participate in the study

Presence of co morbidity considered by the assessing clinician to overshadow the effect of the angina

Poor cognitive ability

Ongoing anticoagulation therapy; where anticoagulants cannot be safely discontinued without jeopardising patient safety

3 sites
45 patients
1:1 randomisation at PMT
SCS + UC vs UC alone

Add SCS to usual medical care and compare to medical care alone A+B vs B
Centres can provide SCS (experienced) and usual care
Treatments to start within 6 weeks of randomisation

Number of electrodes, contacts and type of IPG not specified
Greater than 80% coverage – on table trial and immediate implant
If failed above or intolerant, no implantation but continue as per protocol

Both groups have UC

UK RA guidelines

Published since 1998
Not widely adopted in UK

NRAC, Liverpool
Usual care for UK survey

SGB
Opioids
EECP
SCS
PTCA
CABG
Therapy
Evidence Risk Patient preference
Mersey patient panel
+++++ +++ CBT
TENS +++ ++ -
+
++
+
++
+++
+++
+
+
+
+++
+++
++++
-
+
+
++
+++
++++++

Education session with pain consultant






Content defined
What is RA, Central sensitisation, Anxiety, collaterals
Normal IHD life expectancy, When to call ambulance dilemma
Relaxation, Stay Calm
Role of exercise training
How therapies might work
TENS
Serial SGB’s
Oral opioid or adjuvant analgesia
CBT/exercise programme - PMP
Anything else apart from EECP, CABG, PTCA or PMR
Survey of UK practice may lead to protocol revision

Pilot study using a wide range
Measured by research nurse blinded to therapy
Quality of life – Primary outcome measure

Disease specific – Seattle Angina questionnaire

Non- disease specific – EQ5D, SF36
Functional exercise tolerance

Baseline and 6 months

SCS on, observer blinded, BUT poor reliability

Medication at baseline 3 and 6 months

Cardiac

Pain
Diary of anginal attacks
Adverse events at 3 and 6 months

Defined

Severity, duration, relationship to therapy
Serious adverse events
Healthcare utilisation

At 6 months from Primary & Secondary care

Start Jan 2011

Questionnaire and appointments (4 months)
May 2011

18 Months Recruitment and Follow up
November 2012


Writing report
January-June 2013 Application to NIHR

Spinal cord stimulation is recommended as a treatment option for adults with chronic pain of neuropathic origin who:
 continue to experience chronic pain (measuring at least 50 mm on a 0 –100 mm visual analogue scale) for at least 6 months despite appropriate conventional medical management, and
 who have had a successful trial of stimulation as part of the assessment specified in recommendation 1.3
Spinal cord stimulation is not recommended as a treatment option for adults with chronic pain of ischaemic origin except in the context of research as part of a clinical trial . Such research should be designed to generate robust evidence about the benefits of spinal cord stimulation (including pain relief, functional outcomes and quality of life) compared with standard care
.

Spinal cord stimulation is recommended as a treatment option for adults with chronic pain of neuropathic origin who:
 continue to experience chronic pain (measuring at least 50 mm on a 0 –100 mm visual analogue scale) for at least 6 months despite appropriate conventional medical management, and
 who have had a successful trial of stimulation as part of the assessment specified in recommendation 1.3
Spinal cord stimulation is recommended as a treatment option for adults with chronic pain of ischaemic origin

21-26 May 2011
Neuromodulation: Technology that Improves Patient Care
Featuring:
• World-Renowned Faculty
• Pre-Conference Sessions on the
Fundamentals of Neuromodulation &
Bioengineering; Neurotech Business Ventures
• Main Sessions on: Pain; The Brain; The
Heart; Gastrointestinal & Urological
Dysfunction & more!
www.neuromodulation.com