The disease model of psoriasis developed here represents a global picture of the concepts and domains of psoriasis while providing support for patient-based assessments as endpoints in clinical trials. Itch was identified as a characteristic symptom of psoriasis in the literature review and included as one of the patient-reported symptoms of psoriasis in the disease model. The majority of physicians and patients indicated that itch was the most important symptom of psoriasis. Clinicians agreed in their interviews with the relevance of itch as an important symptom in psoriasis. Furthermore, physicians noted that itch can often be recalcitrant to traditional treatments. In assessing the three qualities of itch (importance, severity, and troublesomeness), patients with severe psoriasis rated itch as more severe on the 10-point visual analogue severity scale and were more likely to select the most severe anchor of 10 (48% with severe psoriasis compared with 0% of mild psoriasis).
Itch, or pruritus, has been shown to be one of the most embarrassing  and distressing  symptoms for patients with psoriasis. This diagnostic symptom of psoriasis has profound effects on HRQoL [2, 17–22]. The affective dimension of itch (described by patients as "unbearable," "worrisome," bothersome," and "annoying"), but not the sensory dimension of itch (described by patients as "burning," "stinging," and "crawling like ants"), is a significant predictor of depression, distress, and sleep impairment in patients with psoriasis . To date, the importance and relevance of itch as a symptom in psoriasis patients has not been systematically assessed. Itch therefore represents an important PRO in clinical trials that should be considered when assessing the efficacy of treatment. Our study was not designed to determine causality between components (eg. symptoms and HRQoL) of the disease model. Better measures of itch should provide further insight into the relationships between triggers and aggravating factors and itch, as well as the effects of itch on HRQoL.
The results of the focus groups in this study are consistent with data from other focus groups  and a questionnaire-based study  that have documented the importance of itch to patients with psoriasis. Also consistent with these previously reported studies were the patients' identification of stress as an aggravating factor for itch and the negative impact of itch on sleep [19, 22]. The results of these studies confirm the link between the impact of psoriasis symptoms and HRQoL in patients with psoriasis, as demonstrated in the disease model of psoriasis.
PROs used in clinical trials can provide fundamental information from the patients' perspective about the symptoms of psoriasis and the subsequent impacts that symptoms have on patients' lives. PROs are also fundamental in evaluating treatments in clinical trials to support approval, develop labeling, and substantiate potential advertising claims from a regulatory perspective. The results of our study demonstrate that itch matters to patients and clinicians, and assessment of itch should be included as a PRO in clinical trials of drugs used to treat psoriasis. The instrument used to assess itch should be clinically meaningful and be validated for reliability and responsiveness [23, 24]. Other components of the disease model are also important; however, many of the items related to HRQoL can be captured in existing measures, such as the DLQI, SF-36, and EQ-5D.
The disease model of psoriasis developed in this study, in addition to the data from the physician interviews and patient focus groups, establishes a framework for the use of a PRO based on itch in clinical trials of drugs to treat psoriasis, in accordance with the first component of PRO development as required by the U.S. FDA [10, 24]. Additional steps are to adjust the conceptual framework and draft the PRO instrument; confirm the measurement model and assess other measurement properties; modify the instrument; and collect, analyze, and interpret data. In accordance with FDA guidelines , the disease model was constructed using data from an extensive review of the literature. Clinician interviews confirmed essential elements of the disease model. Patient focus groups were used to prioritize aspects of psoriasis that are most relevant to patients, including the effects of itch on patients' everyday lives.
A limitation of this study was the nonrandom convenience sampling of both physicians and patients, which may not be representative of all dermatologists or patients with psoriasis. Qualitative research by its very nature requires small sample sizes, limiting the generalizability of the findings. Additionally, this study focused on symptoms of psoriasis; other domains in the disease model are equally important in understanding the impact of psoriasis on patients' lives but were outside the scope of these analyses.
Despite the small sample size, the entry criteria for participation in the study were similar to those used in clinical trials, increasing the likelihood of generalizability of our findings to other patients with psoriasis. All of the patients had physician-confirmed disease and represented the spectrum of disease severity in clinical practice. Because saturation was reached in the grid analysis, the sample size was adequate to meet our objective of achieving a better understanding of the impact of psoriasis on patients' lives.
Our results suggest that improvements in itch will result in improvements in patients' HRQoL. An anti-psoriatic drug that improves the symptoms of itch could therefore support a claim that the drug also improves HRQoL. The disease model reinforces the importance of measuring the components of disease as well as the patients' perspective within the clinical trial setting. In addition to the visual analog scale of itch severity frequently used in clinical trials, our study supports the development of itch questionnaires, such as the one developed by Yosipovitch et al , to fully assess the impact of itch on HRQoL in patients with psoriasis.