Challenges and proposed framework for formative research to inform systematic intervention development in rare and unstudied conditions: The case example of Xeroderma Pigmentosum

Purpose: To outline the challenges of applying existing systematic intervention development approaches in rare diseases, and to propose a novel framework within which these challenges can be met. Background: A gap in the provision of self-management and psychosocial interventions to change behaviour and improve health in rare diseases exists, partly due to the difficulty of conducting formative research in such conditions. Challenges include heterogeneity within already small sample sizes, patient burden, and the absence of prior research to guide decision-making. XP is a very rare inherited disease (~100 UK patients), involving an inability to repair ultraviolet radiation (UVR)-induced damage and increased melanoma risk; the only treatment is complete photoprotection. No research in XP has been conducted outside of the genetic literature. Methods: Using XP and improved photoprotection as a case example, we highlight the necessity of departing from the steps outlined by three intervention development approaches (intervention mapping, UK MRC guidelines for complex interventions, behaviour change wheel), and outline a framework that can be applied to the conduct of formative research in rare diseases. The framework focuses on the sequential or parallel use of mixed-methods (e.g., n-of-1, interviews, reviews of comparable conditions) and the triangulation of gathered data, and provides solutions to challenges including patient burden and the inability to pre-test study materials or intervention content in members of the target population. Conclusions: The proposed framework offers an alternative that may overcome the limitations associated with intervention development in rare diseases, which will hopefully encourage much-needed work in this field

Experiences of stigma over the lifetime of people with xeroderma pigmentosum: A qualitative interview study in the United Kingdom

This study explored experiences of stigma in 25 adults with xeroderma pigmentosum. Analysis of semi-structured interviews revealed the changing nature of stigma over the lifetime. Bullying occurred in childhood, whereas adults were questioned about both their photoprotection and skin damage, often resulting in internalised feelings of stigma. Resilience and rejection of feelings of stigma increased with age and experiences of stigma differed across cultures. Findings indicate a need to develop social skills training to help people reject feelings of stigma. Future research should explore perspectives of families, friends and formal institutions and their potential to cause or reduce feelings of stigma

Ultraviolet radiation exposure to the face in patients with xeroderma pigmentosum and healthy controls:applying a novel methodology to define photoprotection behaviour*

BACKGROUND: In xeroderma pigmentosum (XP), the main means of preventing skin and eye cancers is extreme protection against ultraviolet radiation (UVR). Protection is most important for the face. OBJECTIVES: We aimed to assess how well patients with XP adhere to medical advice to protect against UVR by objectively estimating the mean daily dose of UVR to the face. METHODS: We objectively estimated the UVR dose to the face in 36 patients with XP and 25 healthy individuals over 3 weeks in the summer. We used a new methodology which combined UVR dose measurements from a wrist‐worn dosimeter with an activity diary record of face photoprotection behaviour for each 15‐min period spent outside. A protection factor was associated with each behaviour, and the data were analysed using a negative binomial mixed‐effects model. RESULTS: The mean daily UVR dose (weighted for DNA damage capacity) to the face in the patients with XP was 0·13 standard erythemal doses (SEDs) (mean in healthy individuals = 0·51 SED). There was wide variation between patients (range < 0·01–0·48 SED/day). Self‐caring adult patients had a very similar UVR dose to the face as cared‐for patients (0·13 vs. 0·12 SED/day), despite photoprotecting much more poorly when outside, because the self‐caring adults were outside in daylight much less. CONCLUSIONS: Photoprotection behaviour varies widely within the XP group indicating that nonadherence to photoprotection advice is a significant issue. The timing and duration of going outside are as important as photoprotective measures taken when outside, to determine the UVR exposure to the face. This new methodology will be of value in identifying the sources of UVR exposure in other conditions in which facial UVR exposure is a key outcome, particularly in patients with multiple nonmelanoma skin cancers

Validation of the individualised neuromuscular quality of life for the USA with comparison of the impact of muscle disease on those living in USA versus UK

<p>Abstract</p> <p>Background</p> <p>The Individualised Neuromuscular Quality of Life (INQoL) questionnaire is a published muscle disease specific measure of QoL that has been validated using both qualitative and quantitative methods in a United Kingdom population of adults with muscle disease. If INQoL is to be used in other countries it needs to be linguistically and culturally validated for those countries. It may be important to understand any cultural differences in how patients rate their QoL when applying QoL measures in multi-national clinical trials.</p> <p>Methods</p> <p>We conducted a postal survey of QoL issues in US adults with muscle disease using an agreed translation, from UK to US English, of the same questionnaire as was used in the original construction of INQoL. This questionnaire included an opportunity for free text comments on any aspects of QoL that might not have been covered by the questionnaire. We examined the responses using both quantitative and qualitative approaches. The frequency of the responses in US versus UK populations was compared using appropriate correlation tests and Rasch analysis. A phenomenological approach was used to guide the qualitative analysis and facilitate the exploration of patients' perceptions and experiences.</p> <p>Results</p> <p>The US survey received 333 responses which were compared with 251 UK survey responses.</p> <p>We found that INQoL domains covered all the issues raised by US subjects with no additional domains required. The experiences of those with muscle disease were remarkably similar in the US and UK but there were differences related to the impact of muscle disease on relationships and on employment which was greater for those living in the United States. The greater impact on employment was associated with a higher importance rating given to employment in the US. This may reflect the lower level of financial support for those who are unemployed, and the loss of employment related health benefits.</p> <p>Conclusions</p> <p>INQoL is appropriate for use in US population but there may be differences in the importance that US subject attach to certain aspects of QoL that could be the basis for further study.</p> <p>If these differences are confirmed then this may have implications for the interpretation of QoL outcomes in multi-national trials.</p