NATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE
Proposed Health Technology Appraisal
Recombinant human parathyroid hormone for treating
hypoparathyroidism
Draft scope (pre-referral)
Draft remit/appraisal objective
To appraise the clinical and cost effectiveness of recombinant human
parathyroid hormone within its marketing authorisation for treating
hypoparathyroidism.
Background
The parathyroid glands produce parathyroid hormone, which controls the
levels of calcium and phosphate in the blood. When too little parathyroid
hormone is produced it is called hypoparathyroidism and it causes blood
calcium levels to fall and blood phosphorus levels to rise. Symptoms include a
tingling sensation in the hands and feet, muscle cramps, spasm and
tiredness. People with hypoparathyroidism can also have eye problems, dry,
thick skin, and coarse hair and nails that break easily.
Hypoparathyroidism is most commonly caused by accidental injury to the
parathyroid glands during head and neck surgery. Of those having surgery,
less than 3% develop permanent hypoparathyroidism1. Other causes include
autoimmune diseases, genetic abnormalities, radiation therapy or surgical
removal of the parathyroid glands as a result of cancer, and low blood
magnesium levels. Hypoparathyroidism is associated with an impaired quality
of life and increased risk of depression.
Hypoparathyroidism is a rare disorder affecting approximately 27,000 people
in England and it is estimated that between 6,700 and 8,400 of these people
will be eligible for treatment2.
The aim of treating hypoparathyroidism is to relieve symptoms and improve
patients’ quality of life. Oral calcium supplements and vitamin D analogues
(usually alfacalcidol, or if resistance develops, calcitriol) can be taken to
maintain levels of calcium and other minerals within normal ranges. Treatment
is individually tailored to maintain calcium levels that are high enough to avoid
symptoms of hypocalcaemia but low enough to prevent kidney problems. It is
also recommended that people with hypoparathyroidism follow a highcalcium, low-phosphorus diet. Treatment often cannot resolve all aspects of
the disease such as abnormal bone remodelling and reduced quality of life,
and it is associated with long-term complications such as nephrolithiasis,
nephrocalcinosis, renal impairment, cataracts and cerebral calcifications 3.
National Institute for Health and Care Excellence
Draft scope for the proposed appraisal of recombinant human parathyroid hormone for
treating hypoparathyroidism
Issue Date: January 2017
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The technology
Recombinant human parathyroid hormone (Natpar, Shire Pharmaceuticals) is
a full-length recombinant human parathyroid hormone that exhibits all the
physiological effects of parathyroid hormone and helps to normalise calcium,
phosphate and vitamin D metabolism. It is administered by subcutaneous
injection.
Recombinant human parathyroid hormone does not currently have a
marketing authorisation in the UK for hypoparathyroidism. It has been studied
as an adjunct to standard therapy in single arm clinical trials and in a
randomised controlled trial compared with placebo, in adults who have had
hypoparathyroidism for 18 months or more.
Intervention
Recombinant human parathyroid hormone as an adjunct
to standard therapy
Population
Adults with chronic hypoparathyroidism whose disease
cannot be adequately controlled with standard therapy
alone
Comparators
Established clinical management without recombinant
human parathyroid hormone (oral calcium supplements
and vitamin D analogues such as alfacalcidol or
calcitriol, and a high-calcium and low phosphorus diet)
Outcomes
The outcome measures to be considered include:
Economic
analysis

reduction in oral calcium supplements and
vitamin D analogues

serum levels of calcium

adverse effects of treatment

health-related quality of life

mortality.
The reference case stipulates that the cost effectiveness
of treatments should be expressed in terms of
incremental cost per quality-adjusted life year.
The reference case stipulates that the time horizon for
estimating clinical and cost effectiveness should be
sufficiently long to reflect any differences in costs or
outcomes between the technologies being compared.
Costs will be considered from an NHS and Personal
Social Services perspective.
Other
considerations
Guidance will only be issued in accordance with the
marketing authorisation. Where the wording of the
National Institute for Health and Care Excellence
Draft scope for the proposed appraisal of recombinant human parathyroid hormone for
treating hypoparathyroidism
Issue Date: January 2017
Page 2 of 4
therapeutic indication does not include specific
treatment combinations, guidance will be issued only in
the context of the evidence that has underpinned the
marketing authorisation granted by the regulator.
Related NICE
recommendations
and NICE
Pathways
None.
Related National
Policy
NHS England, May 2016. Manual for prescribed
specialised services 2016/17. Chapter 9.
https://www.england.nhs.uk/commissioning/wpcontent/uploads/sites/12/2016/06/pss-manualmay16.pdf
Department of Health, NHS Outcomes Framework
2016-2017, April 2016. Domains 2 and 3.
https://www.gov.uk/government/publications/nhsoutcomes-framework-2016-to-2017
NHS England, 2013/14. NHS Standard Contract for
Specialised Endocrinology Services (adult) A03/S/a.
https://www.england.nhs.uk/wpcontent/uploads/2013/06/a03-spec-endo-adult.pdf
Questions for consultation
How should ‘chronic’ disease be defined?
Which treatments are considered to be part of established clinical
management in the NHS for hypoparathyroidism?
Are magnesium, phosphate binders and thiazide diuretics used in the UK to
treat hypoparathyroidism in addition to calcium supplements and vitamin D
analogues? If so, what proportion of patients with hypoparathyroidism receive
these additional treatments?
Are the outcomes listed appropriate? Are there any additional outcomes that
should be included?
Are there any subgroups of people in whom recombinant human parathyroid
hormone is expected to be more clinically effective and cost effective or other
groups that should be examined separately?
NICE is committed to promoting equality of opportunity, eliminating unlawful
discrimination and fostering good relations between people with particular
protected characteristics and others. Please let us know if you think that the
National Institute for Health and Care Excellence
Draft scope for the proposed appraisal of recombinant human parathyroid hormone for
treating hypoparathyroidism
Issue Date: January 2017
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proposed remit and scope may need changing in order to meet these aims.
In particular, please tell us if the proposed remit and scope:

could exclude from full consideration any people protected by the equality
legislation who fall within the patient population for which recombinant
human parathyroid hormone will be licensed;

could lead to recommendations that have a different impact on people
protected by the equality legislation than on the wider population, e.g. by
making it more difficult in practice for a specific group to access the
technology;

could have any adverse impact on people with a particular disability or
disabilities.
Please tell us what evidence should be obtained to enable the Committee to
identify and consider such impacts.
Do you consider recombinant human parathyroid hormone to be innovative in
its potential to make a significant and substantial impact on health-related
benefits and how it might improve the way that current need is met (is this a
‘step-change’ in the management of the condition)?
Do you consider that the use of recombinant human parathyroid hormone can
result in any potential significant and substantial health-related benefits that
are unlikely to be included in the QALY calculation?
Please identify the nature of the data which you understand to be available to
enable the Appraisal Committee to take account of these benefits.
NICE intends to appraise this technology through its Single Technology
Appraisal (STA) Process. We welcome comments on the appropriateness of
appraising this topic through this process. (Information on the Institute’s
Technology Appraisal processes is available at
http://www.nice.org.uk/article/pmg19/chapter/1-Introduction)
References
1 NHS Choices. Hypoparathyroidism and hyperparathyroidism. Accessed
October 2016
2 Horizon Scanning Research and Intelligence Centre. rhPTH (Natpar) for
hypoparathyroidism – adjunctive therapy. February 2016
3 Marcucci et al (2016) Natpara for the treatment of hypoparathyroidism.
Expert Opinion on Biological Therapy 16(11):1417-1424.
National Institute for Health and Care Excellence
Draft scope for the proposed appraisal of recombinant human parathyroid hormone for
treating hypoparathyroidism
Issue Date: January 2017
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