Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04244123 |
| Other study ID # |
B00672 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
January 24, 2020 |
| Est. completion date |
January 5, 2023 |
Study information
| Verified date |
April 2023 |
| Source |
Manchester University NHS Foundation Trust |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Non-adherence is a recognized problem with growth hormone treatment in children. In this
study, we aim to utilize web-based information derived from easypod growth hormone injection
devices and easypod connect devices in a nurse-led telephone clinic to improve adherence and
therefore optimize growth. Our primary aim is to test height SDS change over a 12 month
period. Our secondary aims are to test adherence, acceptance/satisfaction and qualitative
assessment.
Description:
Background:
Recombinant human growth hormone (GH) is used in the treatment of short stature due to growth
hormone deficiency, Turner syndrome, Prader Willi syndrome, small for gestational age with
failure of catch up growth, chronic renal failure and SHOX deficiency. Growth hormone is
administered at home as daily injections and given over several years. Administration of
growth hormone involves considerable commitment from parents and families and incurs
significant cost to the NHS in the UK. Current treatment regimens using a range of GH
formulations are not based on drug efficacy, cost effectiveness or cost of treatment.
It is well recognised that adherence to treatment is directly correlated to height
performance in patients receiving GH. Several studies have indicated better height outcomes
through use of technology to enhance patient adherence. The standard model of care of GH
therapy involves patients returning to review appointments with clinicians for GH monitoring
and dose adjustment. This model requires travel to hospitals at regular intervals (3-4
monthly), causing disruption to regular routines, inconveniencing family commitments,
education and school. Importantly, this model does not encourage adherence or compliance with
GH and relies on individual patient and family initiative to ensure treatment delivery.
Alternative and more user-friendly models of care promoting greater adherence to GH are
required to improve efficiency of GH treatment outcomes.
We have proposed a novel model of GH treatment monitoring integrating web-based adherence
information in paediatric endocrine specialist nurse-led telephone clinics. A specialist
nurse-led telephone clinic for management of growth hormone already exists at the Royal
Manchester Children's Hospital (RMCH) and generates positive feedback from parents and
families whilst releasing capacity in face to face growth clinics. The WAIN-MC model
integrates and improves this specialist nurse-led clinic with web-based GH adherence
information as a clinical innovation. The proposed model enables remote monitoring without
travel to the hospital, review of growth performance in relation to adherence information and
improved engagement of parents/families, thereby increasing adherence, satisfaction and
height gain.
Rationale:
Current models of GH treatment are not targeted towards increasing adherence and achieving
improved height gain. It is important to explore alternative models of care using GH that
improve adherence to treatment and result in improved height outcome whilst enhancing patient
satisfaction. The WAIN-MC model represents a clinical innovation which requires testing for
utility in a pilot study prior to wider application in the NHS.
The WAIN-MC feasibility study provides an alternative treatment model that might improve
adherence of treatment, resulting in greater height outcome than with the current standard
model of hospital review. This study is based on a telephone clinic run by specialist nurses
who are able to access information about treatment adherence through easypod connect. This
model enables greater understanding of adherence patterns correlated to height gain without
requiring additional hospital reviews and the stress of frequent visits to the hospital. It
is likely to be better accepted by parents and families, thereby fostering greater adherence
and culminating in greater efficiency of treatment. WAIN-MC represents the application of
digital technology in the achievement of improved treatment outcomes in children receiving GH
treatment.
Previous findings and data from other studies It is well recognised that an important
component of treatment outcome with GH is adherence. However, non-adherence is common among
children and families receiving treatment with height outcomes being limited by and
correlated with the degree of non-adherence [1]. In spite of efforts made by healthcare
professionals, long term adherence with GH treatment is suboptimal and widespread [2], with
one study reporting 30% good adherence [3].
Several devices are available to inject or transject GH for treatment in children. Only one
device records the number of the injections and the efficiency of dose injection administered
- Saizen easypod™ manufactured by Merck Healthcare KGaA. Easypod can also dock into a 4G
connected device, easypod connect™ which uploads adherence as digital information specific to
the patient. A recent study showed good adherence using easypod connect with the magnitude of
2 year catch-up height gain correlated to high adherence levels [4]. In the multi-centred
longitudinal observational study (ECOS study) involving 1190 patients, median adherence with
GH treatment was high at 93.7% in the first year [5]. However, adherence decreased with
increasing treatment duration with adherence rates progressively declining to 87.2% at 3
years, 75.5% at 4 years and 70.2% at 5 years. Thus the use of easypod GH and easypod connect
is strongly associated with good adherence with GH treatment but is unable to prevent the
reduction of adherence rates over longer durations of treatment.
The WAIN-MC clinical innovation integrates easypod connect with the structure of a specialist
nurse-led telephone clinic for additive treatment outcome benefits for each component. It is
expected that the synthesis model will not only reinforce adherence but also sustain this
through regular clinical contact. WAIN-MC is a novel development and therefore has not been
investigated for efficacy.
The following are the likely benefits of WAIN-MC to participants:
1. Improved height gain over 1 year of treatment; initial height gain is likely to
correlate with optimal final height gain at the end of treatment
2. Improved patient and family satisfaction with WAIN-MC, reinforcing further adherence
3. Increased clinic capacity for standard clinic reviews
4. Improved cost efficiency of treatment with favourable financial cost of height gain and
favourable total cost of treatment
5. Serve as a template for future studies in GH treatment and other forms of daily
injectable therapy
Hypothesis:
We hypothesize the following:
1. The WAIN-MC model is a feasible option in the treatment of children with GH.
2. Adherence will improve by 10% from the time of entry to the study to the time at the end
of the study.
3. Children on GH will gain 0.5 SD or more within one year of adopting WAIN-MC
4. Parents and families will find the application of WAIN-MC to their satisfaction and
therefore provide positive qualitative feedback.
Objectives:
The study aims to investigate the utility of a nurse led clinic using easypod connect
web-based GH adherence information in a one year feasibility study. The study will
investigate if adherence with easypod GH improves by combining easypod connect with nurse led
telephone monitoring clinics. The study will also investigate potential improvement in height
gain over 12 months whilst adopting WAIN-MC.
Study design:
This is a feasibility study designed to investigate whether the WAIN-MC model is practical
for use in this population. At present there are 70 patients enrolled on this model, which is
a reasonable sample size to assess variation in auxology outcomes. Taking alpha as 0.05, and
90% power, a sample size of 70 will detect an effect size of 0.41, allowing for 10% dropout.
For the semi-structured interviews not all parents will consent and financial and time
practicalities also constrain the sample size. All 70 patients will be invited to consent and
a random selection of 15 individuals will be selected from those consenting to take part in a
semi structured interview for feedback.
There are no controls groups for this feasibility study. Each patient will serve as his/her
own control with comparison of adherence and auxology data between initial and final visits.
Study Design:
1. Patients All patients who receive easypod GH of age 1-14 years will be approached for
consent to participate in the study. Patients may have any valid cause for short
stature. These may include children with isolated growth hormone deficiency, multiple
pituitary hormone deficiencies, and non-growth hormone deficient conditions such as
small for gestational age with postnatal failure of height gain, chronic renal failure
and Turner syndrome. Patients will be recruited to the study irrespective of diagnosis
and will not be stratified by diagnosis at entry to the study. However, in analysis of
data, subgroup analysis may be performed on groups such as those with isolated growth
hormone deficiency, dependent on the frequency of recruitment.
All patients will be identified at the start of the study. A one month period will be
considered before the study commences to contact families for potential recruitment.
Each patient will remain in the study for 12 months. The active study duration will be
18 months whereby all eligible patients will be recruited and followed up for a 12 month
period. This period will be followed by a buffer period to gather necessary data for
analysis. The timeline of the study is provided in the in Appendix 1
2. Procedures Health Research Authority/Ethical (IRAS 264053) and MFT approval will be
achieved for this study prior to any study procedures commencing. Information for
consent will be provided to the parents of patients eligible to participate in the study
at study initiation.
Paediatric endocrine specialist nurse led face to face appointments at outpatients in RMCH
will be set up on 3 days for explanation and patient recruitment. The appointments will be
led by specialist nurses Sister Julie Jones and Sister Helen Pimlott and overseen by Dr I
Banerjee, CI for the study. Dr Banerjee will undertake consent for this study from parents
and carers.
Standard clinic reviews with hospital visits will continue in parallel. Investigations, dose
changes and other treatment alterations will be continued as part of routine clinical care.
At the initial visit, the following information will be obtained:
1. Adherence information based on easypod connect data over the month previous to study
entry will be recorded in the clinical research form (CRF). A hard copy of a screen
capture image will be stored in the CRF for each patient.
2. Height will be measured by a Harpenden stadiometer at outpatients department in RMCH.
Weight will be measured at the time using weighing scales. Information on age, sex,
height and weight will be entered into the CRF. Puberty will not be assessed but
information on puberty will be obtained from the previous or closest clinic review
correspondence. Auxology (height, weight) will be converted to standard deviation scores
using both UK 1990 centiles and WHO reference standards.
3. The educational qualifications of one or both parents will be noted using the
International Standard Classification of Education (ISCED) 2011
[http://www.uis.unesco.org/Education/Documents/isced-2011-operational-manual.pdf]. The
following categories will be used: 0 pre-primary education, 1 primary education, 2 lower
secondary education, 3 upper secondary education, 4 post-secondary non-tertiary
education, 5 short-cycle tertiary education, 6 Bachelor or equivalent, 7 Master or
equivalent, 8 Doctoral or equivalent.
Following the initial visit, two nurse led telephone monitoring clinics will be set up at 4
and 8 months. Patients and families will be offered a choice of 3 days for each of the 4 and
8 month telephone clinic appointments. Each appointment will last for 20 minutes. The
telephone appointment will be structured in the following format:
1. Ascertain dose of easypod GH, cartridge size of easypod GH and check if supplies are
adequate.
2. Record special circumstances potentially influencing adherence.
3. Parent/carer reported adverse events
4. Obtain recent height and weight data from GP surgery measurements
5. Record advice regarding method of administration, needle size and depth of injection
6. Record parent perceptions of adherence and comparison with easypod connect information
over previous 3 months.
A final face to face nurse led clinic review will be undertaken at outpatients in RMCH.
Patients and families will be offered a choice of 3 days for the final study visit. At the
final appointment, the following information will be obtained:
1. Auxology data
2. Adherence data over previous 3 months
3. Adverse events, if any
4. The highest education status will be re-ascertained in as per the International Standard
Classification of Education (ISCED)] as stated at the initial visit.
A randomly chosen subset (n=15) will be invited to a semi structured interview to provide
feedback. The interview will be conducted by Dr Jacqueline Nicholson, clinical psychologist
at RMCH. The interview will last 30 minutes and will focus on:
1. A 5 point Likert scale of parent perception of satisfaction for WAIN-MC
2. A 5 point Likert scale of parent perception of preference for WAIN-MC as a future
clinical model
3. Qualitative comments of suitability of WAIN-MC to patient care and suggestions for
improvement
(3) Analysis
All variables will be explored to understand their form and completeness using appropriate
descriptive statistics (N [%], mean [standard deviation] or median [interquartile range]) and
graphics. No imputation will take place for missing data, but consideration may be made in
the analyses in the event of large numbers.
The difference in height SDS between entry and final visit will be assessed by paired t-tests
or non-parametric equivalent as appropriate.
Adherence data will be available on a daily basis, but for the main purposes of analysis will
be reported as a percentage for each month (1-12). Trends in non-adherence on a daily basis
will be explored graphically with consideration for recorded information, e.g. consecutive
non adherence due to technical fault or missing doses due to illness or being away on
holiday. Adherence data over a 12 month period will be collated into units of time, i.e.
weeks or months and presented descriptively, with the aid of longitudinal graphs. If
indicated longitudinal models will be used to describe any trends.
The difference in adherence at entry to the study (month 1) and final visit (month 12) will
be tested by paired t-tests or non-parametric equivalent. The change will also be explored
using multivariable regression models to adjust for age, sex, diagnosis and ISCED group.
Univariate and multivariable linear regression model will be used to investigate the effect
of adherence on height SDS, adjusting for age, sex, diagnosis and ISCED group.
Qualitative analysis Results from the patent satisfaction and patient preference
questionnaires will be presented descriptively. Interviews will be transcribed verbatim and
the six stages of Thematic Analysis will be used to analyse the interview data.
