APPENDICES\
APPENDIX 1. Details on the recommendations of NICE (MTA) and SMC
Treatment
Alendronate
Indication
Osteoporosis
NICE
DATE: January 2005
RECOMMENDED
- Use as treatment for secondary prevention
- Confine to specific patient group
- Monitoring of tolerability required
SMC
DATE: October 2005
RECOMMENDED
- Use as treatment option for prevention of fractures
- Confine to specific patient groups
Anakinra
Rheumatoid
Arthritis
Capecitabine
Breast Cancer
(locally
advanced or
metastatic)
DATE: July 2002
NOT RECOMMENDED
- Do not use for insufficient clinical evidence
- Do not use due to poor cost-effectiveness
DATE: March 2003
RECOMMENDED FOR RESTRICTED USE
- Use as per SPc
- Use as 2nd line (both as monotherapy and in combination if
failed other treatments - anthracycline)
- Use with supervision of specialists
Capecitabine
Colon Cancer
Clopidogrel
Acute Coronary
Syndrome
Docetaxel
Breast Cancer
DATE: November 2003
NOT RECOMMENDED
- Do not use for insufficient clinical evidence
- Do not use due to poor cost-effectiveness
DATE: May 2003
RECOMMENDED
- Use as per SPc
- Use as 2nd line (both as monotherapy and in
combination if failed other treatments)
- Monitoring of AEs required
- Use with supervision of specialists
DATE: April 2006
RECOMMENDED
- Use as per SPc (oral)
- Use as monotherapy as adjuvant treatment following
surgery
- Monitoring of AEs required
- Use with supervision of specialists
DATE: July 2004
RECOMMENDED
- Use as per SPc (in combination with aspirin)
- Treatment continued up to 12 weeks
DATE: Sep 2001 and Sep 2006
RECOMMENDED
- Use as per SPc
DATE: July 2005
ACCEPTED FOR USE
- Use as per SPc (oral)
- Use as monotherapy as adjuvant treatment following surgery
- As effective as other treatments but more convenient to the
patients
- Prescribed by specialists
DATE: February 2005
RECOMMENDED FOR RESTRICTED USE
- Use as per SPc (in combination with aspirin)
DATE: September 2005
RECOMMENDED
- Use as per SPc
- Given in combination as adjuvant treatment (early)
Drotrecogin
Sepsis
Etanercept
Psoriatic
Arthritis
Imatinib
GIST
Imatinib
CML
Insulin Glargine
Diabetes
Levetiracetam
Epilepsy Adults
Methylphenidate
ADHD
DATE: September 2004
RECOMMENDED
- Use as SPc
- Confined to most severe patients
- Use by specialists
DATE: July 2006
RECOMMENDED
- Use as per SPc
- Use if patients did not benefit from other treatments
(DMARDs)
- Initiated and supervised by specialists
DATE: October 2004
RECOMMENDED
- Use as 1st line treatment
- Continue if response by specified duration
- Use with supervision of specialists
DATE: October 2004
RECOMMEND
- Use as per SPc
- Use as 1st line treatment
- Confined to subgroups of patients
DATE: December 2002
RECOMMENDED
- Use for Type I diabetes
- Do not use for Type II patients due to insufficient
evidence (unless specified categories)
DATE: March 2004
RECOMMENDED
- Use as SPc
- Use if patients did not benefit from other treatments (as
combination therapy)
DATE: March 2006
RECOMMENDED
- Given in combination as adjuvant treatment
- Cost-effective compared to standard treatments
- Monitoring of toxicity required
DATE: October 2002
RECOMMENDED FOR RESTRICTED USE
- Use as SPc
- Confined to most severe patients
- Use by specialists
DATE: June 2004
RECOMMENDED
- Use as per SPc
DATE: August 2003
RECOMMENDED FOR RESTRICTED USE
- Use with supervision of specialists
DATE: Dec 2002
RECOMMENDED FOR RESTRICTED USE
- Confined to subgroups of patients
- Need of more clinical evidence
- Monitoring required
- Initiated and supervised by specialists
DATE: September 2002
RECOMMENDED FOR RESTRICTED USE
- Use for Type I diabetes
- Do not use for Type II patients due to insufficient evidence
(unless specified categories)
DATE: January 2005
RECOMMENDED FOR RESTRICTED USE
- Use as per SPc
- Initiated by physicians with expertise
DATE: May 2004
RECOMMENDED FOR RESTRICTED USE
Mycophenolate
Renal
Transplant
Olanzapine
Bipolar Disorder
Olanzapine
Schizophrenia
Oxaliplatin
Colon Cancer
Peg Interferon
(alfa-2a and
alfa-2b)
Hepatitis C
Pimecrolimus
Atopic
Dermatitis
Risedronate
Osteoporosis
- Use as per SPc
- Use less costly option
- Initiated by specialist
DATE: September 2004
RECOMMENDED
- Use if intolerant to other treatment
- Confine to subgroups of patients.
DATE: September 2003
RECOMMENDED
- Use as per SPc
- Monitoring of AEs required
DATE: June 2002
RECOMMENDED
- Use as 1st line (oral)
- First option for those with AEs with other treatment,
otherwise use least costly option
- Monitoring of AEs required
DATE: August 2005
RECOMMENDED
- Use as per SPc
DATE: January 2006
RECOMMENDED
- Use only as combination therapy for severe Hepatitis C
- Use also as monotherapy for mild hepatitis C
- Do not use in some groups of patients
DATE: August 2004
RECOMMENDED
- Use as 2nd line only if intolerant to topical
corticosteroids
- Initiated by physicians with experience in dermatology
DATE: January 2005
RECOMMENDED
- Use as treatment for secondary prevention
- Use as 2nd line (under restricted circumstance)
- Initiated by specialists
DATE: December 2004
RECOMMENDED
- Use as per SPc
- Use as prophylaxis in combination with other treatments
- Use by specialists only
DATE: May 2004
RECOMMENDED
- Use as per SPc
DATE: June 2003
RECOMMENDED FOR RESTRICTED USE
- Use as 1st line (oral)
- Intramuscular for those failing oral
- Less side effects than comparators
- Cost-effective compared to other treatment
DATE: October 2005
RECOMMENDED
- Use as per SPc
- Given under supervision of specialists
- Cost-effective treatment
DATE: May 2002
RECOMMENDED
- Use as per SPc
- Supervision of specialists needed
DATE: August 2004
NOT RECOMMENDED
- Do not use due to insufficient clinical evidence of
effectiveness
- Do not use due to insufficient economic evidence
DATE: May 2003
RECOMMENDED
- Use for prevention and treatment
- Monitoring of tolerability required
- Cost neutral and convenient to the patient
DATE: June 2002
RECOMMENDED
- Use as 1st line (oral)
- First option for those with AEs with other treatment,
otherwise use least costly option
- Monitoring of AEs required
DATE: September 2003
RECOMMENDED
- Use as per SPc
- Use as 1st line in combination
- Supervised by specialist
DATE: August 2004
RECOMMENDED
- Use as 2nd only if intolerant to topical corticosteroids
- - Initiated by physicians with experience in
dermatology
DATE: May 2003
RECOMMENDED FOR RESTRICTED USE
- Confined to subgroups of patients
- Use with supervision of specialists
Risperidone
Schizophrenia
Rituximab
NHL
Tacrolimus
Atopic
Dermatitis
Teriparitide
Osteoporosis
DATE: January 2005
RECOMMENDED
- Use as treatment for secondary prevention
- Confine to specific patient group
- Monitoring of tolerability required
DATE: December 2003
RECOMMENDED FOR RESTRICTED USE
- Use as treatment and prevention
- Cost-effective for a subgroup of patients
- Use by specialists
Topirimate
Epilepsy Adults
and children
DATE: March 2004
RECOMMENDED
- Use as per SPc
- Use if patients had not benefited from older
antiepileptic drugs (initially as monotherapy, combined
if monotherapy fails)
DATE: January 2004
RECOMMEDED FOR RESTRICTED USE
- Use as per SPc
- Use if patients had not benefited from older antiepilectic
drugs
DATE: December 2004
RECOMMENDED
- Use as per SPc
- Use as 1st line in combination
- Use only by specialist
DATE: October 2002
RECOMMEDED FOR RESTRICTED USE
- Use as 2nd only if intolerant to topical corticosteroids
- - Initiated and supervised by dermatologists
Appendix 2.
Calculation of net monetary benefit in the case of medications for
osteoporosis.
The third party assessment group informing NICE estimated that approximately 940,000
women aged 50 or more suffer from osteoporosis in the UK [18]. The lifetime risk of vertebral
fracture was estimated to be about one in three (about 310,000 women). The assessment
group also estimated that about 28% of women with osteoporosis had a vertebral fracture at
age 80 (about 260,000 women). Of these, about 21,4% occur in the age group 50 to 59,
28.6% in the age group 60-69 and most of them (almost 50%) in the age group 70-79. Thus,
there will be approximately 55,650 osteoporotic women aged 50 to 59 with previous fractures,
about 74,350 extra cases for women aged 60 to 69, 130,000 for women aged 70 to 79 and an
extra 50,000 cases for women aged more than 80 years.
On the basis of the results in terms of incremental costs and incremental QALYs for
alendronate and risendronate obtained from the assessment group (Matt Stevenson, personal
communication), we have compared the expected net monetary benefit [17] of treating all
women (SMC decision) and restricting treatment to specific sub-groups (NICE decision).
Table 3 shows the net monetary benefit results for women with previous fractures and Tscore –2.5. Assuming a monetary value of £30,000 per QALY, if all women were treated,
both alendronate and risendronate would generate positive population net monetary benefits
(£15,616,878 and 5,570,704, respectively) , while teriparatide would be associated with an
expected negative population net benefit (-£135,483,695). However, if treatment is restricted
to those sub-groups where treatment is cost-effective (age 70 and 80), both alendronate and
risendronate would generate higher population net monetary benefits (£19,040,380 and
£11,497,200, respectively). Thus, if heterogeneity is ignored and both alendronate and
risendronate are given to all women suffering from established osteoporosis, this would result
in a loss of populaton net monetary benefit, compared to more selective use, of £3,423,502
(£2,531,766 + £891,736) for alendronate and £5,926,316 (£4,333,020 + £4,650,741) for
risendronate.
Similar conclusions can be obtained in the case of women with higher risk factors for
subsequent fractures (Table 4). In this situation, while alendronate and risendronate are
associated with positive net monetary benefits for all age groups, the net monetary benefit
(positive or negative) with teriparitide depends on the age group considered. If heterogeneity
is ignored, teriparitide would not be recommended. If heterogeneity is taken into account,
teriparitide would be recommend for patients aged over 70 with an increase in population net
monetary benefit of more than £15,000,000 (£5,354,960 + £ 10,296,050). Although these
values are likely to be overestimated (not all women with osteoporosis and previous fractures
will be candidates for alendronate or risendronate) and they do not take account of the
distribution of patients between treatments, the potential importance and the impact of taking
heterogeneity into account is evident.
Table 3. Incremental costs, QALYs and net benefits for osteoporosis drugs stratified by age (women with previous fractures and T-score
–2.5)
Drug
Age
Incremental
costs (£)*
Incremental
QALYs*
Population
Total net benefit
50
149
0.0044
55650
-891,736
60
139
0.0035
74350
-2,531,766
70
95
0.0056
130000
9,531,730
80
5
0.0065
50000
9,508,650
104
0.0052
310000
15,616,878
50
145
0.0034
55650
-2,350,155
60
135
0.0029
74350
-3,576,161
70
104
0.0047
130000
4,901,520
80
26
0.0053
50000
6,595,500
110
0.0044
310000
5,570,704
50
558
0.0025
55650
-26,948,179
60
553
0.0021
74350
-36,546,966
70
530
0.0039
130000
-53,582,100
80
487
0.0040
50000
-18,406,450
535
0.0036
310000
-135,483,695
(λ=£30,000)*
Alendronate
All Patients
Risedronate
Teriparitide
* compared with no treatment in women with sufficient calcium and vitamin D intakes
Table 4. Incremental costs, QALYs and net benefits for osteoporosis drugs stratified by age (fracture risk doubled for alendronate and
risendronate, quadrupled for teriparitide)
Drug
Age
Incremental
costs (£)*
Incremental
QALYs*
Population
Total net benefit
50
128
0.0089
55650
7,651,040
60
111
0.0070
74350
7,311,282
70
33
0.0112
130000
39,424,320
80
-131
0.0130
50000
25,997,550
50
0.0105
310000
80,384,192
50
128
0.0069
55650
4,333,020
60
112
0.0058
74350
4,650,741
70
92
0.0094
130000
24,791,130
80
-80
0.0106
50000
19,839,850
97
0.0088
310000
53,614,741
50
526
0.0098
55650
-12,900,171
60
511
0.0083
74350
-19,570,333
70
431
0.0158
130000
5,354,960
80
268
0.0158
50000
10,296,050
448
0.0143
310000
-16,809,494
(λ=£30,000)*
Alendronate
All Patients
Risedronate
Teriparitide
* compared with no treatment in women with sufficient calcium and vitamin D intakes