Report on Public Patient Involvement (PPI) event in grant applications

Authors:

  1. SabaBalasubramanian, Senior Clinical Lecturer, Department of Oncology, University of Sheffield
  2. Jon Wadsley, Consultant Oncologist, Weston Park Hospital, Sheffield Teaching Hospitals NHS Foundation Trust

Introduction

Thyroid cancer is the most common endocrine cancer[1]. Differentiated thyroid cancer (DTC, including papillary, follicular and Hurthle cell subtypes) is the most frequent tumour group. Females are three times more commonly affected than males. Thyroid cancer is most frequently diagnosed between 30 and 50 years old. In 2009, there were 2,340 new cases of thyroid cancer in the United Kingdom (UK) (3.5 per 100,000), almost half of which were diagnosed in patients less than 50 years old (CRUK, 2013). The incidence of thyroid cancer has increased by 2.4 fold in the last few decades[2]; higher than any other cancer amongst the United States population[3]. Patients with DTC generally have a very good prognosis. In particular, those with small, well differentiated tumours can expect a 30 year cancer specific mortality rate of around 0.4%[4].

There are three main modalities of treatment of DTC – surgery, radioactive iodine ablation and high doses of Thyroxine to suppress Thyroid Stimulating Hormone (TSH). Patients treated for DTC are at risk of long term treatment related morbidity (TRM) due to a number of reasons - disruption of endocrine physiology caused by damage to adjacent structures during surgery; long term impact of RAI treatment; and high doses of Thyroxine (THST) leading to subclinical hyperthyroidism.

Thyroid surgery and long term morbidity: Current UK guidelines on the management of DTC advise total thyroidectomy in most patients with tumours >1cm diameter. Prophylactic central neck dissection is recommended in some ‘high risk’ patients. Thyroidectomy may be accompanied by unintentional damage to the parathyroid glands (glands involved in calcium regulation), resulting in hypoparathyroidism and hypocalcaemia. This may be transient, resolving within weeks to months of surgery; or permanent, persisting for greater than 6 months. There are several studies examining the incidence of post thyroidectomy hypocalcaemia and short term outcomes. There is a wide variation in reported figures perhaps due to the lack of a unifying definition[5]. The long term effects of hypocalcaemia in the cancer population has, however, not been well characterised.

Oral calcium and/or vitamin D supplementation are often required to treat permanent hypocalcaemia (PH). This can lead to increased calcium excretion in the urine (hypercalciuria) and kidney impairment, with sequelae of chronic anaemia, metabolic disturbances, bone and cardiovascular disease[6]. PH has also been linked directly with bone disease, dental problems[7], development of cataracts[8], brain calcification[9], ECG changes (prolongation of corrected QT interval)[10], seizures[11] and laryngospasm[12].

Further long term treatment related morbidity (TRM) following surgery may result from injury to the recurrent and external laryngeal nerves leading to voice symptoms such as hoarseness, lack of volume and rapid tiring of speech[13]; dysphagia[14] possibly due to changes in oesophageal motility[15]; and Quality of Life outcomes[16].

Radioactive iodine and long term morbidity: Radioactive iodine (RAI) remnant ablation is currently recommended in the majority of patients who have a total thyroidectomy and those with an unfavourable histology[17]. Radioiodine therapy may cause salivary gland problems including sialadenitis and xerostomia[18]. This may further impact on quality of life.

TSH suppression with high doses of Thyroxine and related morbidity: Many patients with DTC are commenced on thyroid hormone suppression therapy (THST) using levothyroxine (LT4) postoperatively. There is a large evidence base supporting the benefits of suppressing TSH[19]. Recent studies however show that in those with very low risk tumours, a low-normal TSH level is acceptable[20] and upcoming revisions to guidelines are likely to reflect this.

There have been some studies examining the long term impact of THST on a number of organ systems, as summarised in the table below.

Organ system / Effects / References
Musculoskeletal / Reduced bone mineral density in women / [21-23]
Reduced muscle mass / [24]
Cardiovascular / Raised mean blood pressure and pulse / [25, 26]
Increased left ventricular mass / [27-29]
Reduced diastolic function / [29-32]
Increased prevalence of atrial fibrillation / [33]
Quality of life / Reduced Quality of Life (QoL) / [24, 34]
Increased frequency of hyperthyroid symptoms / [28, 35]
Coagulation / Greater prothrombotic tendency / [36]
Neuropsychiatric / Impaired cognitive function / [37]

Outline of the proposed grant application

Long term health problems (TRM) in patients with thyroid cancer have not been well studied, particularly in the UK population. Published studies have often included small samples with a relatively short follow up duration. We propose to conduct a large multicentre study to investigate the prevalence and severity of long term DTC TRM in the UK population. The aims are to:

  1. Determine the prevalence and severity of hypocalcaemia, voice change and dysphagia (TRM) in patients with differentiated thyroid cancer.

2. Determine the influence of TSH suppression and treatment related morbidity on the quality of life in patients with DTC.

The proposed study schema is shown below.

The proposed endpoints for analysis are:

Primary

  1. Quality of life over a 5-year period stratified by hypocalcaemia, TSH suppression and radioiodine exposure.
  2. Prevalence and severity of hypocalcaemia and voice change.

Secondary

  1. Bone health at five years stratified by hypocalcaemia and TSH suppression.
  2. Cardiovascular health at five years stratified by hypocalcaemia and TSH suppression.
  3. Renal health at five years stratified by hypocalcaemia and TSH suppression.

We are also being aided by a patient charity (Butterfly UK) in organising an online national survey of patients with Thyroid cancer. This will help us understand the distribution of demographics and ongoing health problems in patients with thyroid cancer, their opinions on what health outcomes are important and their willingness to undergo specific tests/investigations.

The value of the proposed research to the NHS and to patients

As detailed above, differentiated thyroid cancer is becoming more common and affects younger age groups than many other common cancers. Treatment related morbidity in this group has not been well characterised. A comprehensive assessment in a multi-centred setting would facilitate a better understanding of treatment related morbidity (TRM). This would lead to patients and clinicians becoming better informed about the long term effects of the treatments used; and facilitate further research to mitigate these long term effects. The eventual aim is to improve quality of life and clinical outcomes for patients and to reduce the burden of long term morbidity in this group.

A recent survey of clinicians involved in the management of thyroid cancer in the UK showed a wide range of awareness of treatment related morbidity, an agreement that long term TRM is not well defined, that there is a lack of guidelines for monitoring patients, and that further work in this area is required[38].

How the proposed research will build on existing knowledge and contribute to the evidence base

There are few studies on treatment related morbidity in thyroid cancer. Majority of these studies are small and have been carried out in other countries where treatment regimens are different to those used in the UK. The long term effects of hypocalcaemia in particular have not been studied in these patients. We aim to carry out a large multicentre study across a wide range of outcomes to address the gap in knowledge and add to the evidence base. This will be the first large study of this kind in the UK DTC population.

A draft protocol has been circulated to the members of the NCRI Thyroid subgroup and comments have been received. It is agreed that there is a need for such a study to be carried out and several members from various centres across the UK have expressed an interest in participation.

Aim

The aim of the PPI exercise was to determine:

  1. Patients’ perspectives on (any) long term health problems based on personal experience.
  2. Patients’ views on the proposed study design, potential ethical issues and any obstacles to participation.

The objective was to carry out ‘focus group’ discussion with patients with differentiated thyroid cancer in Sheffield to enable us to meet the above aims.

Methods

Patients were identified from a list of individuals who had thyroid cancer treatment and were attending the thyroid cancer follow up clinic under the care of a consultant oncologist (JW) in the last 6 months. These individuals were then contacted by a clinician or clinical nurse specialist either in person during their clinic visit or over the telephone. They were invited to take part in a ‘focus-group’discussion session lasting for 1-2 hours. They were also informed about the nature of the project and the aims of the discussion.

Individuals interested in taking part were asked to attend the session at the Royal Hallamshire hospital. The session was moderated by Mr Balasubramanian, Dr Wadselyand Ms Quarrelland minuted by Ms Reid. In addition to minutes being taken, an audio recording of the session was done after verbal consent was given by all patients taking part in the session. At the end of the session, participants were invited to complete a feedback form.

Refreshments were provided and travel expenses were offered to be reimbursed. Vouchers worth £15.00 were distributed after the event.

Results

Around 17 patients expressed a willingness to take part. Only nine said that they may be able to take part in the session on the specified day. Of these, only five attended on the day. There were 3 female and 2 male patients; all of whom had treatment for differentiated thyroid cancer. Case notes were not reviewed, so no further details were available.

Content of discussions: Following general introductions and explanation of the purpose of the meeting, a short power point presentation was used to explain the background to the research; the aims and objectives of the research project; the role of the research participant and the implications of the research finding for patients and clinicians. The session then focussed on the following main issues:

  1. Experiences of problems with thyroid cancer treatment – One patient wondered if his quality of life was affected by the treatment and wondered how the research will be able to answer this question as this was subject to a number of other factors. Two participants mentioned problems with hypocalcaemia after treatment for thyroid cancer.
  2. Willingness to have extra tests for the purposes of research – All patients were willing to undergo the extra tests. Two participants specifically raised the issue of abnormal test results and what options were available to research participants in this scenario. They were reassured that all abnormal test results would be acted upon as per standard practice and the patient and their GP informed of this outcome. It was also explained that many test results would be in the ‘borderline’ or ‘indeterminate’ range and the implications of these results may not be clear, in which case, no specific action would be taken. There was some discussion on how results (normal or abnormal) will be communicated to patients and whether a systematic approach will be taken for all patients. The trial steering group will have to discuss this further and specify a course of action in the protocol.
  3. Willingness to travel to hospital for research purposes – None of the patients had any objections to travel to hospital to help with the research. There was a discussion on compensation for travel costs. While some patients did not think it was a problem, there was concern that this would be a limiting factor for other patients. It was thought that if costs of travel could be offered, that would encourage more patients to take part.
  4. Any other potential concerns or issues – There were queries about whether GPs would be aware of patients’ participation in this study. It was explained that this would be the case.
  5. Any particular requirements or support patients may need – The time in the course of patients’ management when they would be contacted about potential involvement in the study was discussed. Participants were reassured that this would be at least one year after completion of radio-iodine treatment.
  6. Personal willingness to participate in the study –All participants indicated personal willingness to participate in the study.
  7. Willingness to getting involved further in this study–Four of the five participants were willing to get involved in the design and conduct of the study, if required.

Overall, the participants appeared to have enjoyed the session and their feedback has been summarised in Table 1.

Table 1.Summary of feedback provided by participants attending the focus group discussion.

No. / Question / Number answered / Response
1 / I understood the purpose of this ‘focus group’ discussion / 5 / 4 strongly agreed and 1 agreed
2 / I received adequate information at the start of the event / 5 / 4 strongly agreed and 1 agreed
3 / I felt that my contributions were listened to and valued / 5 / All strongly agreed
4 / The quality of the venue, and arrangements were appropriate to the nature of the event / 5 / 4 strongly agreed and 1 agreed
5 / I enjoyed the experience of participating in this event / 5 / All strongly agreed
6 / Can you let us know in what ways, if any, the researcher could have improved your experience? / 4 / 1. “N/A”
2. “No”
3. “Everything was fine”
4. “The experience was good, in respect of speaking to other people who have had thyroid cancer. I don’t feel it needed improvement at all”
7 / Would you be interested in getting involved in the design and conduct of this clinical study? / 5 / 4 said ‘yes’ and one said ‘no’.
8. / Thinking about your experience, would you be willing to take part in similar activities in the future to help other researchers develop their ideas and their research proposals? / 5 / 4 said ‘yes’ and one said “would need to consider”.
9. / Name and contact details / 5 / All provided details
10. / Other comments / 0 / -

Discussion

Despite the small numbers of patients that attended, there was a good discussion of the issues involved and all participants participated enthusiastically and made useful contributions.

All participants understood the purpose of the ‘focus group’ and the need for the research study. Participants were in general very positive about the study and were generally happy to discuss their own experiences. They were willing to consider the prospect of being enrolled in the study. The majority were also keen to be further involved in the design and conduct of the study, as and when required.

The need for additional tests primarily for research purposes and the significance of any abnormal test results were discussed in detail. It was interesting to listen to patients’ views and perceptions on how test results were to be dealt with.

The limitations of this exercise was that the number of participants that attended on the day was small. Arranging the session in the holiday period probably accounted at least partly for the low attendance.

Taking PPI forward:

We intend to involve one or two of the participants from this focus group in the design of the trial; especially in the formulation of information sheets and consent forms.

Summary

The focus group was a useful experience for the authors involved. The intention is to apply to the CRUK for funding a multi-centre observational study of long term treatment morbidity in patients with differentiated thyroid cancer.

Acknowledgements

We acknowledge the following individuals for their help and support in conducting the event successfully.

  1. Sr Gill Quarrell and her colleagues Ms Judy Darwent and Ms Maxine Eades – for their help in inviting patients and help in organising the event
  2. Ms Sarah Mason – for organising the event – contacting patients, arranging venue and refreshments and distributing the vouchers
  3. Ms Deborah Reid – for taking minutes and transcribing the recordings of the meeting

Appendix

The total expenditure was £76.80.Detailed breakdown of how the funding was spent is as follows.

  1. ‘Sainsbury’s gift card’ vouchers – sent to 5 patents (£15.00 each) - £75.00
  2. Travel expense (claimed by one participant) – £1.80

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