Scottish Medicines Consortium
Guidance to Manufacturers for Completion of New
Product Assessment Form (NPAF)
Supplement on medicines for end of life and very
rare conditions
November 2015
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medicines for end of life and very rare conditions November 2015
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Produced by: SMC Secretariat
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Review date:
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1.
Background
The Scottish Government’s inquiry into access to new medicines concluded that existing costeffectiveness thresholds are not always appropriate when considering medicines for end of life or very
rare conditions. The Scottish Medicines Consortium (SMC) has been asked to apply more flexible
approaches in the evaluation of these medicines, as a first step in a wider process to determine
Scotland’s requirement for a value-based approach for the health technology assessment of new
medicines.
The new processes include the option of an input from a Patient and Clinician Engagement (PACE)
group for these kinds of medicines. They also include the opportunity to submit a new or revised
Patient Access Scheme (PAS). In addition, the assessment process for ultra-orphan medicines
involves a broad decision-making framework.
This supplement provides guidance to manufacturers on how the changes to process apply to full
submissions and re-submissions made to SMC.
2.
Categorisation
SMC defines end of life medicines and medicines used to treat orphan (very rare) and ultra-orphan
(extremely rare) conditions as follows:
End of life medicine: A medicine used to treat a condition at a stage that usually leads to death within
three years with currently available treatments.
Orphan medicine: A medicine with European Medicines Agenecy designated orphan status (i.e.
conditions affecting fewer than 2,500 people in a population of 5 million) or a medicine to treat an
equivalent size of population irrespective of whether it has designated orphan status.
Ultra-orphan medicine: A medicine used to treat a condition with a prevalence of 1 in 50,000 or less
(or around 100 people in Scotland).
The definitions of orphan and ultra-orphan status are based on the full population of the licensed
indication relevant to the submission, irrespective of whether or not the company wishes SMC to
consider the product when positioned for use in a sub-population of the licensed indication. The
definition of end of life medicine may be based on a sub-population of the licensed indication where
the manufacturer provides adequate justification.
3.
Process for submissions for medicines with end of life and orphan status
A submission for an end of life medicine or a medicine used to treat an orphan condition should use
the standard New Product Assessment Form (NPAF), which has been updated to take account of the
additional information required by SMC.
SMC asks pharmaceutical companies to state in their submission whether the medicine is in one or
more of the categories outlined in section 2 (above) and to provide evidence for this. Companies
should ensure the evidence provided is clearly documented and referenced in section 2 of the NPAF.
SMC will consider the company’s case and confirm eligibility for consideration as an end of life
medicine or a medicine used to treat an orphan condition prior to the New Drugs Committee (NDC)
meeting. Within this time period, the company may be asked to provide further justification of status.
When making a submission for an end of life medicine or a medicine used to treat an orphan
condition companies have the opportunity to indicate whether, in the event of NDC ‘not
recommended’ advice, they wish their submission to be considered under the end of life/orphan
process. If the company requests their submission be considered under the standard process they
cannot request a PACE meeting at a later stage.
3.1
Completion of the New Product Assessment Form
If opting for assessment via the PACE process, in addition to completing the NPAF the company must
provide additional information on the categorisation of the medicine in section 1 (registration details).
They should also provide supporting evidence and rationale for this categorisation in section 2
(overview and positioning). For end of life medicines, this should include an estimate of median
overall survival with currently available treatments for the relevant population. For medicines used to
treat orphan and ultra-orphan conditions, this should include data on prevalence of the condition in
the full licensed indication in NHS Scotland. All supporting evidence should be fully referenced.
All other sections of the NPAF remain unchanged. The economic analysis required for evaluation of
end of life medicines and medicines used to treat orphan conditions remains the same as for all full
submissions and re-submissions, as set out in section 6 of the NPAF.
3.2
Evaluation of medicines with end of life or orphan status
Submissions are assessed by NDC according to standard process. If NDC’s draft advice for an end
of life medicine or a medicine with orphan status is ‘not recommended’ the pharmaceutical company
will be offered the opportunity to confirm that they wish to go ahead with consideration of the medicine
under the PACE process. They will then have the option to submit a brief statement for consideration
at the PACE meeting at the same time as they provide comments on the NDC Detailed Advice
Document (DAD). A copy of the template for the company PACE statement can be found on the SMC
website. This statement should focus on additional information covering factors that may not be fully
captured within conventional clinical and economic assessment, such as:
 unmet need
 severity of the condition
 added value of the medicine for the patient and family / carers
 place in therapy and
 details of any sub-groups whom the medicine may specifically benefit.
It should not contain any Commercial in Confidence (CiC) information.
The output from the PACE meeting will be a major factor in the SMC decision.
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At this point the company will also have the option to submit a new or revised PAS aimed at improving
the cost-effectiveness of the medicine. Where a new or revised PAS is submitted, it should be sent to
the SMC secretariat together with the company comments on the NDC DAD (two weeks from company
receipt of the NDC advice). The following should be included within the company comments:


A table of results which clearly shows the impact of the new/revised PAS on the base case
incremental cost-effectiveness ratio (ICER) and all sensitivity analysis ICERs currently reported in
the NDC advice. This should include the revised incremental cost figures where these have been
quoted in the NDC advice.
A copy of the summary table on budget impact for the new/revised with-PAS scenario
In addition, a supplementary document should be provided showing the impact of the new/revised PAS
on all the ICERs presented as sensitivity analysis within the NPAF (i.e. any results tables and tornado
diagrams) and also the with-PAS results corresponding to any additional analyses that had been
requested by the economic assessor prior to or following the NDC meeting. A revised budget impact
template to take account of the new/revised PAS is also required.
This additional information will then be reviewed by the SMC assessment team prior to the SMC
meeting.
4.
Process for submissions for medicines with ultra-orphan status
In SMC’s routine contact with companies about submission requirements after receipt of a positive
opinion from the Committee for Medicinal Products for Human Use (CHMP), the company will be
asked to indicate whether the product will be used to treat an ultra-orphan condition (see definition in
section 2) and to provide supporting evidence, i.e. data on disease prevalence for the full indication in
NHS Scotland. SMC will confirm to the company that the medicine meets the criteria for the ultraorphan assessment process before the submission is made.
A submission for an ultra-orphan medicine should use the standard NPAF, which has been updated
to take account of the additional information requirements.
4.1
Completion of the New Product Assessment Form
A submission for a medicine used to treat an ultra-orphan condition requires completion of Appendix
A ‘Ultra-orphan decision-making framework’ in addition to the pharmaco-economic case and budget
impact template provided in sections 6 and 7 of the NPAF. Companies should consult the SMC
Guidance to Manufacturers for good practice guidance on all economic evaluations.
For appendix A, the table below sets out the factors companies should consider when completing the
NPAF. In some cases the information required will be a summary of other information within the
NPAF.
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Decision making criteria
Nature of the condition

Impact of the new technology






Costs to the NHS and Personal
Social Services



Value for money


Impact beyond direct health
benefits and on specialist
services




Guidance on evidence
Description of symptoms and functioning with
current treatment
Limitations of current treatment options
Effect on carers’ quality of life
Summary of key efficacy findings from section 3 of
NPAF
Summary of any important adverse events
associated with treatment from section 4 of NPAF
Summary of key clinical effectiveness points from
section 5 of NPAF including clinical significance of
health gain associated with treatment
Discussion of spectrum of benefits within the patient
group and potential for treatment continuation rules
Summary of year 1 and year 5 gross and net budget
impact from section 7 of the NPAF, with and without
PAS where relevant.
Assessment of any significant budget impacts falling
on any non-NHS organisations
Summary of key uncertainties in relation to budget
impact
Summary of the base case cost-effectiveness ratio
or cost-consequence analyses, from the economic
analysis in section 6.
Summary of key sources of uncertainty in the
economic analysis and impact on base case costeffectiveness ratio
Impact of the technology in allowing patients to
contribute
to
society
/
improve
family
functioning/continue in education
Impact on carers quality of life of the new treatment
(note development of formal tools such as Carer
Experience Scale)
Cost-effectiveness ratios showing the adoption of a
wider perspective on costs and benefits
Assessment of impact on NHS staffing,
infrastructure and training requirements
SMC recognises the challenges in providing robust economic evaluations for medicines used to treat
ultra-orphan conditions given the nature of the data available. A cost-utility analysis is requested for
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such medicines as this allows comparability with other medicines across the value for money
spectrum. However, where an evaluation using QALYs is not feasible, SMC will accept costeffectiveness analysis using appropriate natural outcome measures. Cost-consequence analysis may
also be provided where the submitting company judges that there are multiple relevant outcomes not
readily captured within a QALY based assessment or cost-effectiveness analysis using a single
outcome measure. SMC appreciates that in some conditions the economic evaluation will have
significant uncertainty, but an estimate is still required.
Given the nature of extremely rare ultra-orphan conditions, submitting companies may also wish to
provide a sensitivity analysis supporting the base case economic evaluation that adopts a wider
perspective than the conventional NHS perspective. This will permit the evaluation to reflect wider
costs and benefits relevant to the patient and their carer, such as out of pocket expenses, lost
earnings and carer quality of life gains from the new treatment.
4.2
Evaluation of medicines used to treat ultra-orphan conditions
NDC meeting:
A submission for a medicine that will be used to treat an ultra-orphan condition will continue to be
assessed as normal by NDC on the basis of its clinical and economic case before consideration by
the SMC Committee. An economic evaluation to indicate the value for money of the medicine will
therefore still be required, but with the flexibility in approach as described in section 4.1 above. NDC
will also review the information presented by the company in Appendix A but this will not be part of the
decision-making process for NDC. If the draft NDC advice is ‘not recommended’, the pharmaceutical
company will also be offered the opportunity to request a PACE meeting and / or to submit a new or
revised PAS.
SMC meeting:
SMC will adopt a broader decision-making framework, examining the nature of the condition, impact
of the medicine, impacts beyond direct health benefits and costs to the NHS using the criteria set out
above. As such, the economic analysis will be a factor within the decision-making framework but will
not be the predominant factor in the SMC decision.
As part of its review process, SMC will assess the information the company has provided within
Appendix A as well as other sources of evidence to populate the framework, e.g. from SMC clinical
experts, Patient Group submissions and, where relevant, the output from PACE meetings. This will
ensure SMC is provided with as complete a picture as possible of the relevant aspects upon which
the decision will be based.
The SMC DAD for medicines used to treat ultra-orphan conditions will include a section describing the
relevant information contained within the ultra-orphan decision-making framework. This will replace
the health economic summary section of the DAD.
File name: S:\Scottish Medicines Consortium\SMC Process
Documents\Current\Guidance for Manufacturers supplement for
medicines for end of life and very rare conditions November 2015
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Produced by: SMC Secretariat
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