Aim

To summarize the validity of the following outcome measures:

• Dermatology Life Quality Index (DLQI)
• Short Form (36) Health Survey (SF-36)
• Physician Global Assessment (PGA)
• Psoriasis Area Severity Index (PASI)
• Psoriasis Symptom Diary.

Findings

Dermatology Life Quality Index

The DLQI is a widely used dermatology-specific quality-of-life instrument. It is a 10-item questionnaire that assesses six different aspects that may affect quality of life.^24,35 These aspects are symptoms and feelings, daily activities, leisure, work and school performance, personal relationships, and treatment.^24,35 The maximum score per aspect is either 3 or 6, and the scores for each can be expressed as a percentage of either 3 or 6. Each of the 10 questions is scored from 0 (not at all) to 3 (very much), and the overall DLQI is calculated by summing the score of each question resulting in a numeric score between 0 and 30 (or a percentage of 30).^24,35 The higher the score, the more quality of life is impaired. In terms of the effect on a patient’s life, the meaning of the DLQI scores is as follows:³⁶

• 0 to 1 = no effect
• 2 to 5 = small effect
• 6 to 10 = moderate effect
• 11 to 20 = very large effect
• 21 to 30 = extremely large effect.

The limitations associated with the DLQI are as follows:

• Concerns have been identified regarding unidimensionality and the behaviour of items of the DLQI in different psoriatic patient populations with respect to their age, gender, culture, etc.³⁶
• The patient’s emotional aspects may be under-represented and this may be one reason for unexpectedly low DLQI scores in patients with more emotionally disabling diseases such as vitiligo. To overcome this, it is suggested that the DLQI be combined with more emotionally oriented measures such as the mental component of the SF-36 scales, or the Hospital Anxiety and Depression Scale.³⁶
• The non-availability of benchmarks for the MCID of DLQI scores in general dermatological conditions is also a limitation, although there have been some attempts to determine these differences for specific conditions such as psoriasis.³⁶
• The DLQI may lack sensitivity in detecting change from mild to severe psoriasis.³⁷

Medical Outcomes Study (Short Form [36] Health Survey)

The SF-36 is a general health status instrument that has been used extensively in clinical trials in many disease areas.¹⁷ The SF-36 consists of eight health domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health.¹⁸ For each of the eight categories, a subscale score can be calculated. The SF-36 also provides two component summaries: the physical component summary (PCS) and the mental component summary (MCS), which are derived from aggregating the eight domains according to a scoring algorithm. The PCS and MCS scores range from 0 to 100, with higher scores indicating better health status. The summary scales are scored using norm-based methods, with regression weights and constants derived from the general US population. Both the PCS and MCS scales are transformed to have a mean of 50 and a standard deviation of 10 in the general US population,¹⁸ enabling scores to be meaningfully compared across different studies.²² Therefore, all scores above or below 50 are considered above or below average for the general US population.^18,22

Validity and reliability of the SF-36 in patients with psoriasis is lacking; however, in one systematic review by Frendl and Ware³⁴ that observed SF-36 concordance and its MCID across many different indications in studies that looked at drug therapy effectiveness, the SF-36 was observed to be responsive (when compared with primary clinical measures) in patients with psoriasis. In addition, of the 10 psoriasis studies identified, net PCS or MCS improvement of at least 3 points was observed in 70% of these studies.

The MCID for either the PCS or MCS of the SF-36 is typically between 2.5 and 5 points,^19-21 with the developer of the SF-36 suggesting a threshold of 3 points for the MCID with a corresponding standard deviation of 0.3.²²

Physician Global Assessment

The PGA is used to determine a single estimate of the patient’s overall severity of disease at a given point in time. Various PGAs have been used in psoriasis with different descriptions and scores.³⁸

Psoriatic lesions are graded for induration, erythema, and scaling based on scales of 0 to 4, which are then averaged over all lesions.³⁹ The Table 13 highlights the scoring for induration, erythema, and scaling:

The sum of the three scales are added and then divided by three (I + E + S ÷ 3) to obtain a final PGA score, as follows:

• 0 = cleared, except for residual discolouration
• 1 = minimal—majority of lesions have individual scores for I + E + S ÷ 3 that average 1
• 2 = mild—majority of lesions had have individual scores that average 2
• 3 = moderate—majority of lesions have individual scores that average 3
• 4 = severe—majority of lesions have individual scores that average 4.

The PGA is more subjective than the PASI in that there is no attempt to quantify the individual elements of plaque morphology or body surface area (BSA) involvement.^26,27 There have also been fewer studies using PGA than PASI. This outcome is considered reliable using test–retest data and internal consistency.²⁷ However, inter-rater reliability due to variability, especially in untrained observers, is poor.²⁷ Many studies now employ only the final value of clear or almost clear as treatment success. Although it would seem the PGA may be less likely to be open to interpretation, different studies have used different definitions of clear or almost clear, making comparisons between treatments difficult.²⁷ Construct and content validity are considered strong within a study, but comparison with other studies, as well as relationship to other methods, are problematic due to the variability in data collection, analysis, and reporting method.²⁷

Psoriasis Area and Severity Index

The PASI is a widely used instrument in psoriasis trials that assesses and grades the severity of psoriatic lesions and the patient’s response to treatment. It produces a numeric score ranging from 0 to 72. In general, a PASI score of 5 to 10 is considered moderate disease and a score higher than 10 is considered severe. A 75% reduction in the PASI score (PASI 75) is the current benchmark for most clinical trials in psoriasis and the criterion for efficacy of new psoriasis treatments approved by the FDA.²⁹

In calculating the PASI, severity is determined by dividing the body into four regions: head, upper extremities, trunk and lower extremities that account for 10%, 20%, 30%, and 40% of the total BSA, respectively.⁴⁰ Each of these areas is assessed separately for erythema, induration, and scaling, which is rated on a scale of 0 (none) to 4 (very severe). Extent of psoriatic involvement is graded as follows:

• 0 = no involvement
• 1 = 1% to 9%
• 2 = 10% to 29%
• 3 = 30% to 49%
• 4 = 50% to 69%
• 5 = 70% to 89%
• 6 = 90% to 100%.

The following formula is used to calculate the PASI score:

PASI = 0.1 (E_n + I_n + S_n) A_n + 0.2 (E_u + l_u + S_u)A_u + 0.3 (E_t + l_t + S_t)A_t + 0.4(E_l + l_l + S_l)A_l where E = erythema, I = induration, S = scaling, A = area, h = head score, t = trunk score, u = upper extremities, and l = lower extremities score.⁴⁰ PASI 75 is a dichotomous scale (Yes/No); PASI 75 means the patient achieved ≥ 75% improvement from baseline PASI score.

A number of limitations of the PASI have been identified and include the following:

• The PASI has been criticized as not correlating the clinical extent of the disease with quality of life and the psychological stress caused by psoriasis. The patient’s measure of quality of life is often worse than the physician’s-rated clinical severity.⁴¹
• There are significant inter-rater reliability issues regarding the measurement of BSA.^26,28 There has been some work regarding the development of imaging and analysis systems to objectively measure BSA.⁴²
• PASI scores can vary substantially between experienced and inexperienced physicians, raising concerns for inter-rater reliability.³⁸
• Improvements in PASI score are not linearly related to severity or improvements in psoriasis.^26,29 The extent of psoriatic involvement is measured using a scale of one to six and the areas corresponding to each score are non-linear.
• Some severe disease (clinically) may be scored low. For example, scores as low as 3 (on palms and soles) may represent psoriasis that disables a patient from work and other life activities.
• Most patients fall into a narrow band of scores, thereby decreasing the usefulness of the full range of scores (i.e., scores above 40 are rare).²⁸ The validity of this scale may be overrated, in part because of the skew toward lower scores.³⁰
• There is little research on the reliability of the assessments for erythema,, and induration, together with overall PASI scores.²⁸
• Criterion validity is restricted by the lack of a “gold standard” measure of psoriatic severity.⁴³
• The PASI lacks sensitivity as erythema, scaling, and induration are scored with equal weight within each of the four body regions. Thus, a reduction in scaling with a concomitant increase in skin erythema could be recorded with the same PASI score.
• Improvement of the histological phenotype of psoriasis can be underestimated by the percentage improvement in PASI (e.g., reduction of T cells, loss of K16 expression and reduction in epidermal thickness).²⁹
• Little work has been done to determine the clinical relevance of derived PASI scores.²⁸

Psoriasis Symptom Diary

The Psoriasis Symptom Diary is a 20-item, psoriasis-specific, electronic diary to assess symptom severity, symptom bother, and disease impact.^31,32 Patients are asked to recall their disease experience over the preceding 24 hours.^31,32 The severity and bother of the following symptoms are assessed: itching, stinging, burning, pain, scaling, and skin colour.^31,32,44 Impact items ask about patient embarrassment, restricted movement due to psoriasis, and avoidance of activities requiring interaction with other people.^31,32 A 0 to 10 numeric scale is used to assess impact, symptom severity, and symptom bother; higher scores indicate more severe impact, bother, or severity (0 = symptom not experienced, 10 = symptom “as bad as you can imagine”).^31,32 Patients are prompted to respond to questions about bother only when they have indicated a score greater than 0 for the severity questions.³² For example, if a patient indicates a score greater than 0 for skin cracking, they are then asked how bothered they are by their skin cracking. Responses for skin colour are categorical and include: pink; light red or brown; bright red or purple; deep, dark red, purple or brown; grey, white, or silver.^31,32 The Psoriasis Symptom Diary was developed in accordance with the US Food and Drug Administration’s guidelines for development of new patient-reported outcome instruments, which require patient input in the instrument development.^31,44

The MCIDs for Psoriasis Symptom Diary severity items (itching, burning, stinging, cracking, pain, and scaling) and change in skin colour are estimated to be 2.0 to 3.0.³² An anchor-based approach was used to determine the MCID; means and standard deviations for Psoriasis Symptom Diary item scores were calculated and compared with levels of change on the Patient Global Impression of Change.³² The Psoriasis Symptom Diary has shown good construct validity; symptom severity items were associated with the Investigator’s Global Assessment (IGA) and PASI, while other items are associated with the DLQI.^32,44 Items on itching for the Psoriasis Symptom Diary are associated with the Pruritus Visual Analogue Scale, DLQI, IGA, and PASI.^32,44 The Psoriasis Symptom Diary has also shown good discriminant validity, sensitivity to patient change,³² and treatment benefit.⁴⁴

The Psoriasis Symptom Diary has several limitations. The tool was developed using a small sample of patients.³¹ Additionally, its validity was assessed using a predominantly Caucasian patient population (96% Caucasian), and it may not be generalizable to other populations; this is especially a consideration for items such as skin colour.³² As a daily diary, compliance with the tool outside of the clinical trial environment is yet to be examined.³²

Conclusion

Several instruments are used when assessing psoriasis disease severity. The PASI is one of the most widely used tools. While it has some noted limitations, the PASI is considered the gold standard for measuring severity of psoriasis.⁴² The Psoriasis Symptom Diary is used to assess a patient’s symptom experience.³¹

Quality of life measures are also important in the assessment of psoriasis severity. The DLQI is a dermatology-specific quality of life measure. DLQI has been validated for use in the psoriasis patient population, with an estimated MCID of 3.2.²³ The EuroQol 5-Dimensions Health-Related Quality of Life Questionnaire (EQ-5D) is a general health–specific quality-of-life measure. There is evidence for the concurrent validity of the EQ-5D in the psoriasis patient population, as it correlates well with DLQI and PASI.⁴⁵ Quality of life remains an important consideration for assessing severity of disease for patients with psoriasis.