A qualitative investigation of the relevance of skin irritation and self-confidence bolt-ons and their conceptual overlap with the EQ-5D in patients with psoriasis

Objectives A number of bolt-ons have been proposed for the EQ-5D, including two psoriasis-specific bolt-ons, skin irritation and self-confidence. The study investigates and compares the relevance and comprehensiveness of these psoriasis-specific bolt-ons and the EQ-5D-5L and explores the potential conceptual overlaps between the existing five dimensions and the two bolt-ons. Methods Psoriasis patients were purposively sampled according to age and gender. Semi-structured interviews, where participants were asked to complete the EQ-5D-5L and the bolt-ons while thinking aloud, were conducted. Probes were used to investigate the thought processes of patients regarding the dimensions, wording, recall period and relevant concepts not captured by the EQ-5D-5L and bolt-ons. Data were analysed thematically. A focus group was used to confirm the findings. Results Overall, 16 patients completed the interviews. Sixteen and fifteen patients considered skin irritation and self-confidence relevant areas to describe psoriasis problems. Three patients considered itching a form of discomfort, and thus, pointed out a potential overlap between pain/discomfort and skin irritation. Twelve patients reported overall 10 general health- or psoriasis-related concepts that are not captured by the EQ-5D-5L, including itching, social relationships and sex life. Eleven patients reported that the recall period of the EQ-5D-5L might be subject to bias because of the daily or within-day fluctuations of their symptoms. Conclusions The skin irritation and self-confidence bolt-ons contribute to improve content validity of the EQ-5D-5L in patients with psoriasis. The qualitative approach taken in this study expands the existing methodological framework for the development and testing validity of bolt-ons for the EQ-5D. Supplementary Information The online version contains supplementary material available at 10.1007/s11136-022-03141-y.


Introduction
Decision makers in healthcare rely on evidence from costutility analyses to judge the value of health interventions. Such analyses require health-related quality of life (HRQoL) data that enable the estimation of quality-adjusted life years (QALYs). The EQ-5D is the most commonly used HRQoL measure in estimating QALYs, recommended by over 20 health technology assessment bodies worldwide [1][2][3]. In general, the EQ-5D exhibits good validity and responsiveness across a broad range of health conditions and settings [4,5]. However, there may be areas of HRQoL the general public or patients perceive as missing from the EQ-5D, limiting its content validity [6,7]. Adding bolt-on dimensions to the EQ-5D specific to a certain patient population or culture is considered a solution to improve content validity. A recent systematic review identified 26 different bolt-on dimensions to the EQ-5D [8]. Examples include cognition [9], sleep [10], social relationships [11], vision, hearing and energy/ tiredness [12]. Studies have used different methods to identify new bolt-on dimensions for EQ-5D including qualitative (e.g. interviews, focus group), quantitative (e.g. factor analysis, latent class analysis or pairwise choices) or mixed methods. [8,11,13,14]. However, qualitative assessment of selected bolt-on dimensions is limited [15,16].
The EQ-5D is one of the most frequently used generic measure of HRQoL in patients with psoriasis, including large observational studies and clinical trials [17][18][19]. Two psoriasis-specific bolt-ons (EQ-PSO) have been developed for the five-level EQ-5D (EQ-5D-5L), one physical (i.e. skin irritation) and one mental (i.e. self-confidence) [15]. Being among the first few bolt-ons, the EQ-PSO was primarily designed to explore methodological feasibility for the development of bolt-ons [15]. During the development of EQ-PSO, four candidate dimensions (skin irritation, skin appearance, self-confidence and social/relationship difficulties) were identified through a literature review, qualitative semi-structured interviews with patients and consultation with a clinical expert, and exploratory factor analysis was used to select the final two dimensions. Improved responsiveness of the EQ-PSO was confirmed in pooled data of three clinical trials using multiple language versions [20]. Although translations exist (n = 48), qualitative evidence documenting the content validity of the EQ-PSO in different languages and cultural contexts is only available from the development study undertaken in the UK [15]. Moreover, it is unclear if there are any conceptual overlaps between the skin irritation and selfconfidence dimensions and the existing five dimensions. An earlier study with burn patients found a moderate correlation between itching as rated on a visual analogue scale and the pain/discomfort dimension of the EQ-5D-5L [21]. It may also be assumed that self-confidence is, to some extent, captured by the dimension of anxiety/depression.
The objectives of our study were therefore to (1) investigate and compare the relevance of the content, comprehensiveness and comprehensibility of EQ-5D-5L and EQ-PSO in Hungarian patients with psoriasis; and (2) explore the potential conceptual overlaps between the existing five dimensions and the two bolt-ons.

Methods
The study design, data analysis and reporting followed the Consolidated criteria for reporting qualitative studies (COREQ) checklist [22].

Study design and participants
Qualitative one-on-one interviews and a focus group were carried out between November 2020 and June 2021 among Hungarian psoriasis patients. Patients were recruited via a local psoriasis patient association in Budapest, Hungary. Patients were sampled using a convenience sampling technique. While stringent quotas were not used, the recruitment intended to achieve heterogeneity in the patient population in terms of age, gender and clinical characteristics, e.g. disease severity and types of treatment. Interviews were conducted until data saturation, whereby additional interviews did not generate any important new themes in the qualitative analysis [23]. Study inclusion criteria were as follows: i) aged 18 years of above; ii) diagnosed with psoriasis by a dermatologist; iii) cognitive ability to read and interpret questions in Hungarian and iv) signed written informed consent. A subgroup of the interviewed patients was invited to a focus group to discuss the findings of the thematic analysis. In response to the COVID-19 pandemic, online video interviewing was offered for those patients that refused the face-to-face interaction. Face-to-face interviews and the focus group were held in an office at the Corvinus University of Budapest. Patients received a gift card of 5,000 HUF (≈14 euro) in return for participation.

Interviews
All interviews were conducted by two of the authors (F.R. and A.B.), both of whom had previous interviewing experience. The interview procedure combined elements of concurrent think aloud, where participants verbalize their thoughts while completing the questionnaire, and verbal probing [24]. We used this approach as we were interested in exploring patients' underlying thought processes rather than exact responses to the questionnaire items. [25]. A topic guide was developed by the research team that included a dermatologist with experience in treating psoriasis patients. After the pilot-test with two patients, small revisions were made to the topic guide including adding a ranking question about the most and least relevant dimensions. The final interview guide comprised of three sections. In the first section, the aims of the study and the interview process were explained to each patient. Then they were asked about their experiences with psoriasis and important aspects of health and health-related quality of life and how these were impacted by psoriasis. In the second section, patients completed the EQ-5D-5L descriptive system, followed by the EQ VAS and EQ-PSO descriptive system (i.e. five core dimensions and the two bolt-ons). The ordering of the three measures was fixed across the interviews. Patients were asked to concurrently verbalise their thoughts when completing the questionnaires and probes were only used to further investigate these. In the last section, patients were asked to directly compare the EQ-5D-5L and EQ-PSO descriptive systems. At the end of each interview, patients completed a short questionnaire about their sociodemographic and clinical background.

Focus group
A focus group was conducted to confirm the key results of the interviews and to provide an opportunity to clarify any uncertainties. Patients reporting an overlap between the boltons and the five dimensions or providing useful suggestions on the improvement of bolt-ons were selectively invited to the focus group based on their responses during the individual interviews. The focus group was led by one of the authors (F.R.) using a topic guide developed by the research team specifically for the focus group. Another researcher (A.B.) was also present as an observer to take notes. At the beginning of the group discussion, patients were asked to fill in the EQ-PSO (including EQ VAS).

Measures
The EQ-5D-5L comprises a five-dimension descriptive system and a visual analogue scale (EQ VAS) with endpoints of 0 (worst health you can imagine) and 100 (best health you can imagine) [26]. Each of the five dimensions of the descriptive system (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) have five response options: no problems, slight problems, moderate problems, severe problems and extreme problems/unable to [27]. The summary of the responses on the five dimensions give the descriptive profile that can be converted into a utility value (index score) based on societal preferences. The EQ-PSO attaches two additional dimensions to the EQ-5D-5L, skin irritation and self-confidence, both with five response options [15]. For skin irritation, itching is mentioned as a supporting example both in the dimension heading and response options ('I have no itching', 'I have slight itching', etc.). The official Hungarian versions were used for both the EQ-5D-5L and EQ-PSO.

Data analysis
All interviews as well as the focus group were audiorecorded and transcribed verbatim. Thematic analysis was carried out by three researchers with expertise in health outcomes research [28]. First, all transcripts were read by one of the authors and the initial themes were inductively derived. Categories and sub-categories were developed to describe emerging themes. A customized extraction matrix was developed in Microsoft Excel 2016 and categories and sub-categories were reported, with their associated interview IDs. Disagreements were resolved through regular discussions within the team. Quotes were selected to support the main categories and subcategories.

Ethics
The study protocol was approved by the Research Ethics Committee of the Corvinus University of Budapest (No. KRH/342/2020).

Sample characteristics
A total of 21 patients with psoriasis were recruited, three of whom withdrew. Two participants did not show up, resulting in a final sample of 16 patients. For 15 of them, we conducted the interview face-to-face. The mean interview duration was 59 min (range 41-91 min). No important new themes emerged after the eleventh interview, confirming that data saturation was attained. The sample had a good spread of age groups, was balanced in terms of gender, was well educated and had heterogeneous clinical characteristics. Detailed characteristics of the participants are presented in Table 1.

Impact of psoriasis on HRQoL
Patients reported 35 aspects on how psoriasis impacted on their lives which were grouped into six concepts: triggers, physical symptoms, mental health consequences, HRQoL consequences, searching for a cure and coping ( Fig. 1). Skin scaling was the most commonly mentioned troubling symptom of psoriasis, followed by itching and scratching. A few patients experienced painful cracking and bleeding of the skin. Among adverse physical consequences of psoriasis, patients frequently reported problems with their social relationships, leisure activities, mobility and limitations in clothing choices due to their visible skin symptoms. These were connected to mental health consequences, such as feeling unattractive, being stared at by others and having to frequently inform others that psoriasis is not contagious or caused by poor hygiene.

Comparing EQ-5D-5L and EQ-PSO
Results of the thematic analysis were summarized under the following themes: content of dimensions, overall relevance, missing concepts, ranking of dimensions, overlap of dimensions, suggested changes, response levels, EQ VAS and recall period.

Content of the EQ-5D and EQ-PSO
Generally, patients interpreted the five dimensions as intended. However, three patients (19%) interpreted 'dressing myself' not as an ability to dress but rather as psoriasis influencing the clothes they can wear, e.g. "My scalp is scaling so I cannot really wear black tops and this is very bad especially that I have to wear black at one of my workplaces and I continuously keep on shaking my top as it looks like I have dandruff". Another patient said that "I also have a problem with washing myself because I have to pay attention to what cosmetics I use". There was a considerable agreement about the meaning of skin irritation since all patients responded to this dimension taking into account their perceived level of itch. However, four patients mentioned skin irritation being independent from itch and one patient emphasized the difference between these two: "Well, it is also possible that a skin irritation hurts but does not itch. It is like all bugs are insects, but not all insects are bugs". For the majority of patients, self-confidence covered their problems with social relationships due to psoriasis and over one-third of patients interpreted this dimension as a belief in oneself or being a valued person.

Relevance of the EQ-5D-5L and the EQ-PSO
The instructions in the descriptive systems were clear and easily understandable for all patients. In total 38% of the patients considered the EQ-5D-5L covered important aspects of HRQoL: "Overall, I find the questionnaire good because this is what a human being is made of, and these are the most important ones [dimensions] in my opinion, too". Other patients expressed concerns about the questionnaire, such as irrelevance of some dimensions in the context of psoriasis: "Well, I cannot connect these first four topics to psoriasis and myself". Two patients noticed the EQ-5D-5L is relevant for detecting the impact of severe psoriasis on patients and recognized the generic nature of the questionnaire. For example, "It is much more relevant for those patients that have joint symptoms or whose condition is more severe" and "here, many of the questions are not related to psoriasis, but to the problems of an elderly person in general."  Sixteen (100%) and fifteen (94%) patients considered the skin irritation and self-confidence bolt-ons as important areas in psoriasis, respectively. All patients rated the EQ-PSO better than the EQ-5D-5L to describe their problems with health-related quality of life, e.g. "the topics of the skin irritation and self-confidence which are, can be said, the two most important aspects of this problem or disease". Figure 1 shows that the EQ-PSO was well aligned with nearly all important impacts of psoriasis raised by patients, with the exception of skin scaling and lost time due to having psoriasis.

Missing concepts
Overall, 11 (69%) patients indicated 16 missing themes for the EQ-5D-5L and 12 (75%) patients indicated 11 missing themes for the EQ-PSO. These missing concepts were summarized under three large categories: general health-related, psoriasis-related and non-health-related concepts. In the EQ-5D-5L, the most commonly reported missing concepts were social relationships (n = 8) with a number of other concepts highlighted by three or less participants. Itching as a missing concept was raised by only one patient. Limitations in clothing (i.e. preference for Fig. 1 Concept map of the impact of psoriasis on patients' lives and EQ-5D-5L and EQ-PSO content coverage. AD = anxiety/depression, CO = self-confidence, HRQoL = health-related quality of life, MO = mobility, PD = pain/discomfort, SC = self-care, SI = skin irritation, UA = usual activities. Orange dimensions refer to the EQ-5D-5L and green to the two psoriasis-specific bolt-ons covering visible skin symptoms or avoidance of wearing dark colours to hide flaking skin) was considered missing by two patients. There were fewer missing concepts identified in the EQ-PSO with social relationships identified by five participants ( Table 2). The majority of the remaining themes were suggestions for other background information to solicit in a more general questionnaire designed for psoriasis patients, e.g. presence of psoriatic arthritis,

Ranking of dimensions
In the EQ-5D-5L, over one-third of patients considered usual activities and anxiety/depression the most relevant dimensions, whereas half of the patients indicated selfcare as being the least relevant one ( Table 3). The relevance of dimensions substantially changed when the two bolt-ons were added to the EQ-5D-5L. In the EQ-PSO, skin irritation was identified as the most relevant dimension, followed by self-confidence, whereas self-care and anxiety/depression were the least relevant dimensions.

Overlap between dimensions
Several minor conceptual overlaps were identified between the seven dimensions (Table 4). Two patients described washing oneself as part of both self-care and usual activities, two patients reported a potential overlap between anxiety and discomfort and one patient reported an overlap between depression and discomfort.
For the two bolt-on dimensions, three patients considered 'itch' a form of discomfort, and thus, pointed out a potential overlap between pain/discomfort and skin irritation: "I rather have a moderate discomfort, I do not have much pain in my joints, the patches do not hurt either, they rather itch". Self-confidence showed an overlap with anxiety/depression (anxiety n = 1, depression n = 1 and both n = 1) according to three patients. n/a n/a n/a n/a 5 36 0 0 Self-confidence n/a n/a n/a n/a 4 29 1 7 All are relevant 1 7 0 0 1 7 0 0 hurt either, they rather itch Self-confidence* Anxiety 2 13 003: Anxiety could also belong to the self-confidence, because whoever does not have self-confidence they are probably anxious Depression 2 13 009: Self-confidence overlaps a bit with depression. It might be possible to rephrase 'depression' to ask if it causes lack of self-confidence P002: When I think of anxiety it reminds me something which makes me constantly anxious, some problem, something which is there all the time, but stress comes as if I may be stressed about something today but maybe I will be stressed again only on Saturday or Sunday… Well, I would not really call stress as anxiety… I would rather put 'stress' or 'everyday problems' here [instead of anxiety] 'Depression' is a too strong word, replace it with 'mood disorder' 2 13 002: Respondent: The word depression may be a bit too strong… Because of the stigma, so one knows that this is the problem but it is still quite bad to face this… Interviewer: And what would you use instead? Respondent: Let's say, mood disorder Add 'stress' 1 6 006: I think stress would be more easy to understand for people, I might write stress next to depression Skin irritation 'Skin irritation' is too narrow 1 6 006: I see this [itching] as small as walking in mobility, the other topics are much bigger and more comprehensive… it is like, let's say, a little toe hurts or the middle and I take that out of pain, so I feel that this itch is just one thing in this whole problem… Add 'skin scaling' and 'skin cracking' 3 19 004: I would add skin scaling and cracking to the irritation because, for me, when it is worse then it cracks Add 'flaking skin' 1 6 P001: Psoriasis comes together with an excessive skin production and it is extremely horrible when one sweeps 200 g of skin from everywhere, everywhere… by the morning the skin gets dry and scaly, it is like snowing. Well, this may be added to skin irritation because it is a form [of skin irritation] too Add 'skin symptoms of bad smell' 1 6 002: I have a strong sense of smell… and in connection to skin irritation that it is not only irritation, for example, itch, but I specifically feel like my skin is rotting Self-confidence

Suggested changes
Ten patients suggested changes in the EQ-5D-5L or EQ-PSO dimensions (Table 5). Changes included the use of wider descriptors for mobility so that it included other motor abilities and for skin irritation, by extending the range of symptoms described beyond itching (e.g. skin scaling, skin cracking or skin flaking). Few patients suggested adding further supporting examples to other dimensions, e.g. 'flaking skin' to usual activities, 'frustration' to pain/discomfort, 'stress' to anxiety/depression and 'self-esteem' to self-confidence. The self-care, pain/discomfort and anxiety/depression dimensions were sometimes suggested to be separated. Three wording changes were proposed, the replacement of 'washing' with 'skin care', 'anxiety' with 'stress' and 'depression' with 'mood disorder'.

Response levels
Six patients (38%) reframed the response levels when completing the EQ-5D-5L or EQ-PSO (Online Resource 1). Of these, five patients used the response levels as a 'frequency scale' and one patient considered 'level of bother' for at least one dimension. This reframing most commonly occurred for mobility, pain/discomfort and skin irritation. Five patients reported problems with the level modifiers, including difficulty differentiating between levels 1 and 2 (for mobility) and levels 4 and 5 (for pain/discomfort, anxiety/depression and skin irritation).

EQ VAS
Patients provided a wide range of interpretations of the endpoint labels 'the best health you can imagine' (= 100) and 'the worst health you can imagine' (= 0) (Online Resource 2). Most patients interpreted EQ VAS as generic and only a few patients used it as a psoriasis-specific scale. For example, when interpreting '0' two patients referred to "when one's whole body is covered with psoriasis". The instructions of EQ VAS were clear for the majority of patients; however, two patients mixed up the endpoints '0' and '100'.

Recall period
Several participants did not use the stated recall period but intended it as in general for the EQ-5D-5L (62%), EQ VAS (25%) and EQ-PSO (31%). Six participants reported that they would have provided identical answers if a different recall period had been asked: "There is no difference between today and the other days of the week or other days of the month". Eleven patients reported that the recall period of the EQ-5D-5L and EQ-PSO might be subject to bias because of the daily or within-day fluctuations of their symptoms: "in fact this is changing as dynamically if we had done this an hour ago I would have answered certain questions differently than now".

Focus group
Eight patients were invited to the focus group, five of which attended (three women and two men). The discussions lasted 94 min (excluding the introduction of each patient). Three of the five patients considered itch a form of discomfort and responded to the EQ-PSO accordingly, whereas two patients reported their level of itching only in the skin irritation dimension. Of note, during the interviews these three patients did not mention itching as discomfort. All patients agreed that skin irritation is a broader category than itching that consists of other symptoms, such as skin scaling and plaquing. Although patients welcomed the idea to add these two symptoms as supportive examples to the skin irritation dimension, two patients cautioned against creating a double-barreled question and reported that their levels of itch and scaling are often not identical (e.g. slight itch and moderate scaling). Two patients described 'skin cracking' as a form of pain/discomfort, while two other patients considered it belonging to skin irritation. One patient said she would report skin cracking both on pain/discomfort and skin irritation. Patients came to a consensus that although self-confidence and anxiety/depression are related constructs there is no overlap between these two dimensions. Of note, one patient in the focus group was among the three patients that had suggested an overlap between self-confidence and anxiety/depression in the individual interviews.

Discussion
This study used qualitative methods to investigate the EQ-5D-5L and EQ-PSO relevance among Hungarian psoriasis patients, focusing on potential conceptual overlap across dimensions. The results show that the EQ-5D-5L is Add 'self-esteem', 'self-identity', 'self-love' 1 6 006: Well, before self-confidence I would add self-esteem because this is a broad concept or I would still add self-identity and also self-love considered relevant in psoriasis, but important concepts of HRQoL may still be missing from its descriptive system. Examples of them include general physical or mental health (e.g. stress, sex life) and psoriasis-specific health (e.g. itching, social relationships, dietary awareness). These findings extend the existing literature on important aspects of health and HRQoL the EQ-5D does not adequately capture in specific populations [6,7]. Furthermore, some of the missing concepts identified by psoriasis patients are covered by already existing EQ-5D bolt-on dimensions, such as social relationships or sexual activity [11,29]. The patient sample almost unanimously confirmed the relevance of the skin irritation and self-confidence bolt-on dimensions to their experience with psoriasis. The majority of patients described these as the two most important aspects of HRQoL in psoriasis. In most cases patients interpreted the EQ-5D-5L or EQ-PSO dimensions as generic and not related to any specific condition. However, in a few instances, certain words or phrases were interpreted as being related to psoriasis. The most prominent example was seen at the selfcare dimension, whereby one-fifth of patients interpreted 'dressing myself' not as an ability to dress but rather as psoriasis influencing the clothes they can wear. Similarly, few patients used the EQ VAS as a scale that measures the proportion of body surface area affected by psoriasis. We believe that mode of administration and the context of the study may be, at least in part, responsible for this effect. Patients were aware of participating in a psoriasis-related interview and this might have led them to overly focus on their skin problems when completing the questionnaires.
A conceptual overlap was identified between the pain/ discomfort and skin irritation dimensions and some patients reported itching as relevant to both dimensions. Yet other patients thought differently and reported itch only in the skin irritation dimension. These disagreements may be attributable to the multifaceted nature of psoriasis. Given the large variability of skin and joint symptoms, including different clinical manifestations, localisations and symptoms, no two patients experience psoriasis the same way. For example, the focus group discussion highlighted that some patients experience itch, while others only report skin scaling, and for others joint symptoms are more bothersome than those of the skin. Based on our results, the skin irritation dimension seems to be a useful bolt-on in this population that might cause some (minor) overlap with pain/discomfort. Conversely, the focus group confirmed that the self-confidence bolt-on dimension is independent from the other dimensions of the EQ-5D-5L and represents a standalone value.
Although patients identified several limitations of the EQ-PSO, one should also consider that adding two conditionspecific items to the EQ-5D-5L cannot be expected to reflect all the important facets of psoriasis. Scale development and valuation implications, such as keeping the number, length and wording of the new dimensions reasonable should also be taken into account. It is possible therefore that what patients consider missing or suggest to improve may confront the researchers' aims and a judgement has to be made as to whether those limitations are sufficient to warrant changing or adding to the measure. For example, during the concept elicitation section of our study, the problems caused by skin scaling were raised by more patients than itching. In agreement with this, several patients proposed extension of this dimension by adding other frequent psoriasis skin symptoms beyond itching. However, by doing so, one may risk of creating a double-barreled question in the skin irritation dimension. Furthermore, when valuing health states, members of the general population may easily imagine itching, while imagining other skin symptoms, such as skin scaling that they most likely have never experienced, could be challenging.
Given the EQ-PSO has a value set developed in the UK [15], our findings are of direct relevance to cost-utility analyses and subsequent reimbursement decisions by providing supporting evidence on the usefulness of the two bolt-on dimensions in psoriasis. Health technology assessment bodies, such as the National Institute for Health and Care Excellence (NICE) [30] in the UK and the Canadian Agency for Drugs & Technologies in Health (CADTH), have already accepted the EQ-PSO in recent submissions for psoriasis treatments' appraisals [31].
Some limitations of the study need to be mentioned. A convenience sampling was used and the majority of patients were related to a patient association. Self-selection bias may also be present as patients voluntarily applied to the study. It is possible, for example, that willingness to participate in such an interview or being a member of a patient association are not independent from one's self-reported health or selfconfidence. Data were collected through two different modes of administration (face-to-face and video-interviewing) which could be a source of potential influence on responses but majority used one mode and there were no differences in what was reported across the modes. Another limitation is that as a substantially large pool of experimental bolt-on dimensions are available for the EQ-5D, it could have been possible to include further bolt-ons in our study, especially those that one may anticipate to be relevant for psoriasis patients (e.g. social relationships, sleep). Lastly, there may be minor differences in semantics between the Hungarian and other language versions of the EQ-5D-5L and EQ-PSO which may prevent the generalizability of these findings to other countries.
In summary, the skin irritation and self-confidence bolton dimensions are particularly pertinent and contribute to improve content validity of the EQ-5D-5L in patients with psoriasis. There is only minor conceptual overlap between the pain/discomfort and skin irritation that does not seem to detract from the added value of the bolt-on item. The qualitative approach taken in this study expands the existing methodological framework for the development and testing validity of bolt-ons for the EQ-5D.