Methods

This was a single‐centre, parallel‐group, active‐controlled, randomised trial

Participants

Inclusion criteria of the trial

• Scalp psoriasis involving at least 25% of the scalp

• Dermatologic sum score (DSS) of at least 3

Exclusion criteria of the trial

• Pregnant or breastfeeding women

• Women at risk of pregnancy

• Subject with ophthalmologic disorders or wearing contact lenses

Washout period

• Specific washout period if concomitant treatment that interferes with psoriasis status or hypothalamic‐pituitary‐adrenal axis function

Baseline characteristics

• Age (years, mean ± SD): A: 38 ± 9; B: 30 ± 10

• Females N (%): A: 3 (21); B: 8 (67)

• DSS (mean ± SD): A: 5.8 ± 1.5; B: 4.7 ± 0.9 ⇒ matched with Total Sign Score (TSS)

• Percent of scalp area affected (mean ± SD): A: 73 ± 28; B: 53 ± 21

Interventions

A: clobetasol propionate 0.05% shampoo, once daily for 4 weeks on dry scalp (N = 14 participants)

B: clobetasol propionate 0.05% gel, once daily for 4 weeks on dry scalp and rinsed off after 15 minutes (N = 12 participants)

Outcomes

1. HPA axis suppression (week 1, 2, 3, and 4)

2. Atrophogenicity (week 4)

3. Ocular tolerability (week 4)

4. Overall safety (week 4)

5. DSS (week 1, 2, 3 and 4) ⇒ matched with total sign score (TSS)

Definition:

HPA axis suppression: pre‐stimulation values of serum‐cortisol below 7 µg/dl, and/or post‐stimulation values lower than 20 µg/dl after 60 minutes of intravenous injection of 0.25 mg cosyntropin

Ocular tolerability: intraocular pressure, results of slit lamp examination, visual acuity assessment, patient rating of burning or sting sensation on a scale from 0 (absent) to 3 (severe)

Overall safety: adverse events probably related to treatment

DSS (0‐9): sum of erythema, adherent desquamation and plaque thickening on score from 0 (none) to 3 (severe)

Visits: baseline, week 1, 2, 3 and 4

Notes

Galderma Laboratories supported the study and employed all authors

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote (page 328): "computer generated randomization list"
Comment: probably sufficient

Allocation concealment (selection bias)

Unclear risk

This was not stated

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Quote (page 330): "Twenty‐five of the 26 enrolled subjects completed the study."
Comment: insufficient reporting of attrition or exclusion, no imputation method reported, but one drop‐out not considered enough to introduce bias

Selective reporting (reporting bias)

Low risk

All reported results were pre‐specified outcomes in the methods section

Other bias

High risk

Quote (page 330): "more females in the clobetasol propionate shampoo group [...] symptom severity and extend of involvement at baseline were worse in the clobetasol propionate shampoo group [...]"

Comment: imbalance of baseline characteristics likely to bias outcome

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Quote (page 328): "due to the different formulations and ways of administration, it was not possible to mask the identity of the treatment from the subjects"

Comment: no blinding of participants performed

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Quote (page 328): "Investigators did not know the treatment provided to the subjects."
Comment: insufficient information about method used to blind investigators

Methods

This was a multicentre, open‐label, parallel‐group, randomised trial

Participants

Inclusion criteria of the trial

• Diagnosis of mild to moderate scalp psoriasis

Exclusion criteria of the trial

This was not stated

Washout period

This was not stated

Baseline characteristics

This was not stated

Interventions

A: calcipotriol solution + tar‐based shampoo, for 8 weeks

B: calcipotriol + non‐medicated shampoo, for 8 weeks

Outcomes

1. 'Marked improvement' (week 8)

2. 'Clearance' (week 8)

3. Mean total sign score (TSS)

4. Investigator assessments of time to achieve treatment success or extent of scalp psoriasis

5. Patient assessments of severity, skin flaking, overall response or acceptability

6. Patient assessment of itching

7. Dermatology Life Quality Index

8. Adverse events

9. Laboratory test parameters

Definition:

TSS: composite score for redness, thickness and scaliness

Visits: baseline, week 8

Notes

This study was published as a letter

Number of participants not stated

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote (page 175): "randomised"

Comment: insufficient detail was reported about the method used to generate the allocation sequence

Allocation concealment (selection bias)

Unclear risk

This was not stated

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

This was not stated

Selective reporting (reporting bias)

High risk

Quote: "A greater reduction in the ‘mean total sign score’ (...) was found for calcipotriol + tar‐based shampoo than calcipotriol + non‐medicated shampoo (p=0.040)."

Quote: "A significant difference in patient assessment of itching in favour of calcipotriol + tar‐based shampoo was found (p=0.032)."

Comment: not all results were reported in sufficient detail. No baseline data for each specific group reported. Study published as letter only.

Other bias

Low risk

No other source of bias identified

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Quote (page 175): "open‐label"

Comment: no blinding performed

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Quote (page 175): "open‐label"

Comment: no blinding performed

Methods

This was a randomised, single‐blind, parallel‐group trial

Participants

Inclusion criteria of the trial

• Older than 18 years

• Stable or worsening psoriasis covering at least 3% of the body surface area (BSA) including skin and scalp

Exclusion criteria of the trial

This was not stated

Washout period

• 2 weeks for topical treatment

• 4 weeks for oral treatment

Baseline characteristics

• Age, mean (years): 49

• Females N (%): 7 (22)

• Psoriasis Area and Severity Index (PASI), mean (SD): A: 12.3 (8.0), B: 9.6 (4.8)

Interventions

A: clobetasol foam, for 2 weeks (N of participants unknown)

B: clobetasol cream (0.05%) plus clobetasol solution (0.05%) regimen, for 2 weeks (N of participants unknown)

Application frequency varied individually according to patients' decision

The study size was 32 participants

Outcomes

1. PASI (week 2)

2. Self administered PASI (SAPASI) (week 2)

3. Quality of life (QOL) (week 2)

4. Patients' compliance (week 2)

5. Patients' satisfaction (week 2)

6. Patients' assessment of ease of medication use (week 2)

7. Cost of treatment (week 2)

Definition:

SAPASI: Assessment according to the PASI performed by the patient

QOL: assessment according to 2 established tools: DLQI and EQ‐5D

Cost of treatment: to find the cost of treating 1% BSA: amount of medication used (in grams) divided by the total percentage BSA treated

Visits: baseline and week 2

Notes

—

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote (page 408): "patients were randomized into 2 treatment groups"

Comment: insufficient detail was reported about the method used to generate the allocation sequence

Allocation concealment (selection bias)

Unclear risk

This was not stated

Incomplete outcome data (attrition bias)
All outcomes

High risk

Quote (page 408): "3 were excluded because of noncompliance: 1 did not return for a second visit, 1 misapplied the foam, and 1 applied the medication intermittently over a 3‐week period."

Comment: per‐protocol analysis performed. Unclear if all drop‐outs belonged to one group. In this case drop‐out rate may be > 10% per group and would introduce relevant bias.

Selective reporting (reporting bias)

High risk

Quote (page 409): "The cost per change of one unit in PASI score was $21.60 for patients using foam and $16.42 for those using cream/solution; the difference was not statistically significant"

Comment: this outcome was not pre‐specified in the method section

Other bias

Low risk

No other potential source of bias identified

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Quote (page 408): "single‐blind design"

Comment: unclear which side was blinded

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Quote (page 408): "single‐blind design"

Comment: unclear which side was blinded

Methods

This was a multicentre, randomised, double‐blind, parallel‐group trial

Participants

Inclusion criteria of the trial

• Age was at least 12 years

• At least 20% psoriatic scalp involvement

• Scalp target area rating of 3 for scaling according to the following scale: 0 (absent), 1 (slight or mild, minimal), 2 (moderate or average, easily discernible), 3 (severe or extensive, markedly evident)

Exclusion criteria of the trial

This was not stated

Washout period

This was not stated

Baseline characteristics

• Total sign score (TSS): A: 8.8, B: 9.5

Interventions

A: augmented betamethasone dipropionate 0.05% propylene glycol lotion twice daily for 3 weeks (N = 84 participants)

B: fluocinonide 0.05% solution twice daily for 3 weeks (N = 85 participants)

Outcomes

1. Total sign score (day 4, 8, 15 and 22)

2. Induration score (day 4, 8, 15 and 22)

3. Scaling score (day 4, 8, 15 and 22)

4. Pruritus score (day 4, 8, 15and 22)

5. Erythema score (day 4, 8, 15 and 22)

6. Global improvement score (day 4, 8, 15 and 22)

7. Clearance of scaling (day 22)

8. Adverse events (drug‐related) (day 22)

9. Withdrawals due to adverse events (day 22)

Definition:

TSS (0 to 12): sum of the scores of the 4 disease parameters

Disease parameter: induration (0 to 3), scaling (0 to 3), pruritus (0 to 3), erythema (0 to 3)

Global Improvement Score: 1 (cleared), 2 (marked improvement), 3 (moderate improvement), 4 (slight improvement), 5 (no change), 6 (exacerbation)

Visits: baseline, day 4, 8, 15 and 22

Notes

—

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote (page 19): "randomized"

Comment: insufficient detail was reported about the method used to generate the allocation sequence

Allocation concealment (selection bias)

Unclear risk

This was not stated

Incomplete outcome data (attrition bias)
All outcomes

High risk

Quote (page 19‐20): "12 patients [...] were excluded from efficacy analysis because baseline entrance criteria for disease severity were not met"

Comment: no intention‐to‐treat analysis performed. Reason for exclusion considered to introduce bias.

Selective reporting (reporting bias)

Low risk

All reported results were pre‐specified outcomes in the methods section

Other bias

High risk

Quote (page 19‐20): "An additional 12 patients [...] were excluded from efficacy analysis because baseline entrance criteria for disease severity were not met."

Comment: these 12 patients with low disease severity were excluded for efficacy evaluations, but included in safety evaluations

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Quote (page 19): "double‐blind"

Comment: insufficient detail was reported about the method used to blind study participants or personnel from the intervention a participant received

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Quote (page 19): "double‐blind"

Comment: insufficient detail was reported about the method used to blind the outcome assessor from the intervention a participant received

Methods

This was a multicentre, prospective, randomised, active‐controlled, double‐blind, parallel‐group trial

Participants

Inclusion criteria of the trial

• Age at least 18 years

• At least 10% psoriatic scalp involvement

• Amenable to topical treatment with a maximum of 100 g of medication per week

• Total sign score (TSS) at least 4 (each subscore at least 1)

• Investigator global assessment (IGA) of at least 3

Exclusion criteria of the trial

• Patients with erythrodermic or pustular psoriasis

• Patients with known or suspected severe renal insufficiency or severe hepatic disorder

Washout period

• 4 weeks for systemic treatment with a potential effect on psoriasis vulgaris (e.g. corticosteroids or immunosuppressants) or PUVA therapy on the scalp

• 2 weeks for UVB or grenz‐ray therapy on the scalp or topical treatment of scalp psoriasis

Baseline characteristics

• Age (years, mean ± SD): A: 48.4 ± 16.5, B: 48.4 ± 14.4

• Females N (%): A: 61 (56.5), B: 59 (53.6)

• TSS (mean ± SD): A: 6.79 ± 1.53, B: 6.81 ± 1.63

Interventions

A: calcipotriol 50 µg/g plus betamethasone dipropionate 0.5 mg/g scalp formulation, once daily for 8 weeks (N = 108 participants)

B: betamethasone dipropionate 0.5 mg/g (same vehicle), once daily for 8 weeks (N = 110 participants)

Patients having 'absence of disease' according to the IGA of disease severity at visits 2 to 5 were allowed to withdraw from the study

Outcomes

Primary outcomes of the trial

1. Total sign score (TSS): absolute change from baseline (week 8)

Secondary outcomes of the trial

1. TSS: percentage change from baseline (week 8)

2. TSS: absolute change from baseline (week 1, 2, 4 and 6)

3. Absolute change in the individual signs of the TSS (week 1, 2, 4, 6 and 8)

4. Absolute change in score for the extent of scalp psoriasis from baseline (week 1, 2, 4, 6 and 8)

5. Investigator's global assessment (IGA) (week 1, 2, 4, 6 and 8)

6. Patient's assessment of treatment success (week 8)

7. Adverse events (AE) (week 8)

8. Serious AE (week 8)

9. Number of patients with at least 1 AE (week 8)

10. Withdrawals due to AE (week 8)

11. Treatment duration (week 8)

12. Treatment compliance (week 8)

Definition:

TSS: sum of the score for each disease parameters ranging from 0 to 12

Disease parameter (0 (no symptoms) ‐ 4 (very severe symptoms)): redness, thickness, scaliness

Patient assessment: 7‐category scale: 0 = worse to 6 = cleared, treatment success: patient rated as 'marked improvement', 'almost clear' or 'cleared'

IGA (6‐point scale): 'absence of', 'very mild', 'mild', 'moderate', 'severe', 'very severe'

Extend of scalp psoriasis: score of 3 = 30% to 49% involvement of the scalp

Visits: baseline, week 1, 2, 4, 6 and 8

Notes

The study was sponsored by LEO Pharma A/S, Ballerup, Denmark

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote (page 108): "randomized"

Comment: insufficient detail was reported about the method used to generate the allocation sequence

Allocation concealment (selection bias)

Unclear risk

This was not stated

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Quote (page 109): "All patients who had received any trial medication and from whom the presence or confirmed absence of adverse events was available were included in the safety analysis set.[...] The primary efficacy criterion was analysed for the intention‐to‐treat (ITT) population [...] a last observation carried forward approach was used."

Comment: missing data have been imputed using appropriate methods. Incomplete outcome data sufficiently reported.

Selective reporting (reporting bias)

Low risk

All reported results were pre‐specified outcomes in the methods section

Other bias

Low risk

No other source of bias identified

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quote (page 108): "double blind [...] same vehicle"

Comment: blinding probably sufficient

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Quote (page 108): "double blind [...] same vehicle"

Comment: insufficient information about method used to ensure blinding of outcome assessor throughout the study

Methods

This was a double‐blind, randomised, active‐controlled trial

Participants

Inclusion criteria of the trial

• Patient with dry scalp psoriasis

Exclusion criteria of the trial

• Patients with skin infection

• Pregnant or breastfeeding women

• Patients with moist lesions

• Concomitant treatment that could affect the course of the disease (e.g. other anti‐inflammatory treatment)

Washout period

• 4 weeks prior to beginning of study for topical corticosteroid treatment

Baseline characteristics

• Scaling: A: 16 (severe), 6 (moderate); B: 13 (severe), 4 (moderate)

Interventions

A: betamethasone dipropionate 0.05% with salicylic acid 2% lotion, twice daily for 3 weeks (N = 22 participants)

B: betamethasone valerate 0.1% lotion, twice daily for 3 weeks (N = 17 participants)

Outcomes

1. Induration (day 7, 14 and 21)

2. Lichenification (day 7, 14 and 21)

3. Excoriation (day 7, 14 and 21)

4. Erythema (day 7, 14 and 21)

5. Crusting (day 7, 14 and 21)

6. Scaling (day 7, 14 and 21)

7. Pruritus (day 7, 14 and 21)

8. Pain (day 7, 14 and 21)

9. Exudation (day 7, 14 and 21)

10. Percentage area of involvement of the lesion (day 7, 14 and 21)

11. Overall evaluation (day 21) ⇒ matched with IGA = "cleared"

12. Number of patients with at least 1 adverse event (AE) (day 21)

13. Withdrawals due to AE (day 21)

14. Withdrawals due to loss to follow‐up (day 21)

15. Withdrawals due to treatment failure (day 21)

16. Time point of first notable improvement

17. Cosmetic acceptability (day 21)

Definition:

Outcome 1 to 9: severity graded on a 4‐point scale 'none', 'slight', 'moderate', 'severe'

Overall evaluation: graded on a 5‐point scale from 'cured' to 'worse'

Percentage area of involvement: estimated approximately

Outcome 16 to 17 : assessed by patient

Visits: baseline, day 7, 14 and 21

Notes

This study was supported by a grant from Schering‐Plough Ltd.

56 participants: 39 psoriasis, 17 eczema

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote (page 203): "Patients were allocated at random"

Comment: insufficient detail was reported about the method used to generate the allocation sequence

Allocation concealment (selection bias)

Unclear risk

This was not stated

Incomplete outcome data (attrition bias)
All outcomes

High risk

Quote (page 203): "Of the 59 patients who entered the trial, 3 were excluded from the analysis because of protocol violations."

Quote (page 205): "Of the 56 patients included in the study, 47 completed the 3‐week treatment regime, and nine were regarded as treatment failures."

Comment: no ITT analysis performed. Unclear if 'treatment failures' (N = 9 participants) were included in overall evaluation or if any imputation method was used

Selective reporting (reporting bias)

High risk

Quote (page 203): "The other symptoms of crusting, induration, lichenification and exudation were not widespread enough at baseline to warrant evaluation."

Comment: not all pre‐specified outcomes reported

Other bias

High risk

Number of participants listed in diagram of overall evaluation (Fig. 3) not consistent with number of participants reported in the text

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Quote (page 203): "treatments were applied in a double‐blind manner"

Comment: insufficient detail was reported about the method used to blind study participants or personnel from the intervention a participant received

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Quote (page 203): "treatments were applied in a double‐blind manner"

Comment: insufficient detail was reported about the method used to blind the outcome assessor from the intervention a participant received

Methods

This was a randomised, single‐blind, active‐controlled trial

Participants

Inclusion criteria of the trial

This was not stated

Exclusion criteria of the trial

This was not stated

Washout period

This was not stated

Baseline characteristics

This was not stated

Interventions

A: hydrocortisone 17‐butyrate 0.1% emulsion, twice daily for 4 weeks (N = 74 participants)

B: betamethasone 17,21 dipropionate 0.05% lotion, twice daily for 4 weeks (N = 76 participants)

Patients could withdraw if healing occurred prior to week 4

Outcomes

1. Erythema (week 2 and 4)

2. Induration (week 2 and 4)

3. Scaling (week 2 and 4)

4. Pruritus (week 2 and 4)

5. Overall severity (week 2 and 4)

6. Clearance (week 4) ⇒ matched with IGA = 'cleared'

7. Adverse events (week 4)

Visits: baseline, week 2 and 4

Notes

This study was published as a conference abstract

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote (page S104): "randomized"

Comment: insufficient detail was reported about the method used to generate the allocation sequence

Allocation concealment (selection bias)

Unclear risk

This was not stated

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No ITT analyses for safety data used: 71 out of 76 (betamethasone group) and 70 out 74 (hydrocortisone group) reported. However, number of missing data not considered as likely to introduce bias significantly.

Selective reporting (reporting bias)

High risk

Only data about clearance reported

Data available for only 1 adverse event

Insufficient reporting about other outcomes assessed

Other bias

Low risk

No other source of bias identified

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Quote (page S104): "single‐blind study"

Comment: insufficient information about which side was blinded

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Quote (page S104): "single‐blind study"

Comment: insufficient information about which side was blinded

Methods

This was a randomised, active‐controlled, parallel‐group trial

Participants

Inclusion criteria of the trial

• Scalp psoriasis

Exclusion criteria of the trial

This was not stated

Washout period

• 2 weeks (no detailed information respecting systemic or topical treatment)

Baseline characteristics

• Age (years, mean (range)): 33.5 (6 to 61)

• Females N (%): 15 (36)

• Total sign score (TSS), mean: A: 5.1, B: 5.4

Interventions

A: calcipotriol 50 µg/ml solution, twice daily for 6 weeks (N = 24 participants)

B: betamethasone valerate 1% lotion, twice daily for 6 weeks (N = 18 participants)

Outcomes

1. TSS (week 2, 4 and 6)

2. Erythema (week 2, 4 and 6)

3. Thickness (week 2, 4 and 6)

4. Scaling (week 2, 4 and 6)

5. Percentage of response to treatment (week 6) ⇒ matched with IGA

6. Recurrences

7. Number of patients with at least 1 adverse event (AE) (week 6)

Definition:

TSS (0 to 12): sum of erythema, thickness and scaling score

Erythema/scaling/thickness score (0 to 4): 0 = absent to 4 = severe

Percentage of response to treatment: percentage of patients categorised into 'worse', 'no change', 'mild', 'marked' (IGA = 'very mild'), 'cleared' (IGA = 'clear')

Visits: baseline, week 2, 4 and 6

Notes

TSS was calculated with sign scores reported in figures 2 to 4 by review author

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote (page 65): "randomized"

Comment: insufficient detail was reported about the method used to generate the allocation sequence

Allocation concealment (selection bias)

Unclear risk

This was not stated

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Data for all randomised patients reported

Selective reporting (reporting bias)

High risk

The pre‐specified outcome of recurrences was not reported in the results section

Other bias

Low risk

No other potential source of bias identified

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

This was not stated

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

This was not stated

Methods

This was a randomised, double‐blind, placebo‐controlled, parallel‐group, multicentre trial

Participants

Inclusion criteria of the trial

• Age of at least 18 years

• Psoriasis of the scalp and/or other hairy areas

• Psoriasis lesions on other areas of the body

• Baseline score (sum of erythema, excoriation, scaling, induration) of at least 6

Exclusion criteria of the trial

• Intolerance of or hypersensitivity to topical corticosteroids

• Pregnant or breastfeeding women

• Acute systemic illness

• Infection of the skin

• Concomitant topical, systemic treatment or PUVA therapy

• Patients with pustular (recalcitrant) psoriasis

Washout period

• 2 weeks for topical corticosteroids

• 4 weeks for systemic, intralesional or inhaled corticosteroids and for PUVA therapy

Baseline characteristics

• Age (years, mean ± SD): A: 49.7 ± 16.9, B: 48.5 ± 16.5

• Females N (%): A: 39 (51), B: 37 (46)

• Disease status: stable N (%): A: 46 (60), B: 46 (58)

Interventions

A: amcinonide lotion 0.1%, twice daily for 3 weeks (N = 83 participants)

B: placebo (vehicle), twice daily for 3 weeks (N = 82 participants)

Patients were allowed to withdraw, if complete clearance occurred prior to week 3

Outcomes

1. Investigator overall evaluation (week 1, 2 and 3) ⇒ matched with IGA

2. Erythema (week 1, 2 and 3)

3. Induration (week 1, 2 and 3)

4. Scaling (week 1, 2 and 3)

5. Excoriation (week 1, 2 and 3)

6. Pruritus (week 1, 2 and 3)

7. Patient's overall evaluation (week 1, 2 and 3) ⇒ matched with PGA

8. Patient acceptability evaluation (week 1, 2 and 3)

9. Adverse events (AE) (week 1, 2 and 3)

10. Number of patients with at least 1 AE (week 3)

11. Compliance (week 1, 2 and 3)

12. Withdrawal due to AE (week 3)

13. Investigator overall evaluation: clearance (week 3) ⇒ matched with IGA = 'cleared'

14. Investigator overall evaluation: excellent (week 3) ⇒ matched with IGA = 'very mild'

Definition:

Overall therapeutic efficacy assessed by investigator (1 to 7): 1 = cleared (complete clearing), 2 = excellent (> 75% improvement), 3 = good (> 50% improvement), 4 = fair (> 25% improvement), 5 = poor (< 25% improvement), 6 = no effect, 7 = exacerbation (clinical signs and symptoms worse)

Outcomes 2 to 6.: rated by investigator on a scale from 0 to 3, 0 = absent, 0.5 to 1.0 = mild, 1.5 to 2.0 = moderate, 2.5 to 3.0 = severe

Patient's overall evaluation (0 to 3): 0 = poor, 1 = fair, 2 = good and 3 = excellent

Patient acceptability evaluation: form with 11 questions

Compliance: count of the returned medication bottles

Visits: baseline, week 1, 2 and 3

Notes

—

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote (page 316): "computer‐generated randomization list designed to produce approximately equal numbers of patients in each study arm"

Comment: probably sufficient

Allocation concealment (selection bias)

Unclear risk

This was not stated

Incomplete outcome data (attrition bias)
All outcomes

High risk

Quote (page 317): "Those patients who met the protocol requirements and had at least one follow‐up visit were included in the analyses of efficacy."

Quote (page 323): "For the evaluable patients, the endpoint evaluation was defined as the patient's last valid evaluation."

Comment: no ITT analysis, but per protocol analysis performed

Selective reporting (reporting bias)

High risk

Quote (page 323): "Both test formulations were cosmetically acceptable to patients."

Quote (page 317): "no formal analysis was performed because there were few adverse events"

Comment: insufficient data about prespecified outcome (patient acceptability, compliance) reported

Other bias

Low risk

No other source of bias identified

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quote (page 314): "double‐blind"

Comment: vehicle‐controlled trial. Blinding probably sufficient.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Quote (page 314): "double‐blind"

Comment: insufficient information about how blinding of assessor was ensured throughout the study

Methods

This was a randomised, blinded, active‐controlled trial

Participants

Inclusion criteria of the trial

• Adult patients

• Psoriasis of the scalp and/or other hairy areas

• Pre‐therapy (symptom) score of at least 6

Exclusion criteria of the trial

• Intolerance or hypersensitivity to topical corticosteroids

• Pregnant or breastfeeding women

• Acute/active systemic illness

• Tuberculosis of the skin

• Systemic fungal or viral diseases of the skin

• Underlying disease that would contraindicate the use of steroids

• Skin disease that was refractory to previous corticosteroid therapy

• Concomitant topical, systemic treatment or PUVA therapy

• Recalcitrant psoriasis not suitable for topical corticosteroid therapy (e.g. acute pustular psoriasis)

Washout period

• 2 weeks for topical corticosteroids

• 4 weeks for systemic, intralesional or repository corticosteroids, antimetabolites and for PUVA therapy

Baseline characteristics

• Age (years, mean (range)): A: 42 (19 to 74), B: 47 (19 to 78)

• Females N (%): A: 14 (48), B: 9 (33)

• Weight (kg, mean (range)): A: 71.7 (39 to 143), B: 85.9 (52 to 143)

• Stable disease status N (%): A: 14 (48.3), B: 16 (59.3)

Interventions

A: amcinonide lotion 0.1%, twice daily for 3 weeks (N = 29 participants)

B: fluocinonide solution 0.05%, twice daily for 3 weeks (N = 30 participants)

Outcomes

1. Investigator overall evaluation (week 1, 2 and 3) ⇒ matched with IGA

2. Erythema (week 1, 2 and 3)

3. Induration (week 1, 2 and 3)

4. Scaling (week 1, 2 and 3)

5. Excoriation (week 1, 2 and 3)

6. Pruritus (week 1, 2 and 3)

7. Patient's overall evaluation (week 1, 2 and 3) ⇒ matched with PGA

8. Patient cosmetic acceptability evaluation (week 3)

9. Adverse events (AE) (week 1, 2 and 3)

10. Number of patients with at least 1 AE (week 3)

11. Withdrawals due to AE (week 3)

Definition:

Overall therapeutic efficacy (1 to 7): 1 = cleared (complete clearing), 2 = excellent (> 75% improvement), 3 = good (> 50% improvement), 4 = fair (> 25% improvement), 5 = poor (25% improvement), 6 = no effect, 7 = exacerbation (clinical signs and symptoms worse)

Outcomes 2 to 6: rated by investigator on a scale from 0 to 3, 0 = absent, 0.5 to 1.0 = mild, 1.5 to 2.0 = moderate, 2.5 to 3.0 = severe

Disease symptoms score (0 to 12): sum of erythema, induration, excoriation, scaling

Patient's overall evaluation (0 to 3): 0 = poor, 1 = fair, 2 = good and 3 = excellent

Patient cosmetic acceptability evaluation: form with 11 questions completed by patient

Visits: baseline, week 1, 2 and 3

Notes

—

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote (page 472): "patients were sequentially assigned to one of the two treatment groups by means of a computer‐generated randomization list"

Comment: probably sufficient

Allocation concealment (selection bias)

Unclear risk

This was not stated

Incomplete outcome data (attrition bias)
All outcomes

High risk

No intention‐to‐treat analysis

Withdrawal due to adverse events: A: 0, B: 1

Patients excluded from efficacy analysis: A: 0, B: 3

Selective reporting (reporting bias)

Low risk

All reported results were pre‐specified outcomes in the methods section

Other bias

Low risk

No other source of bias identified

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Quote (page 471): "blinded comparison"

Comment: insufficient detail was reported about the method used to blind study participants and personnel from the intervention a participant received

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Quote (page 471): "blinded comparison"

Comment: insufficient detail was reported about the method used to blind the outcome assessors from the intervention a participant received

Methods

This was a multicentre, randomised, single‐blind trial

Participants

Inclusion criteria of the trial

• Older than 18 years of age

• History of stable or worsening scalp psoriasis

• Psoriasis involving at least 10% of the scalp

• Baseline score of at least 6

Exclusion criteria of the trial

• Intolerance of or hypersensitivity to topical corticosteroids

• Pregnant women

• Use of topical corticosteroids

• PUVA or UVB therapy within 2 weeks prior to the trial

• Known allergy to topical corticosteroids

• Conditions on the scalp other than psoriasis

• Severe and uncontrolled manifestations of any disease (including psoriasis)

• Concomitant systemic corticosteroids or retinoids

• Known failure to respond to topical corticosteroids within 1 year prior to the study

Washout period

• 2 weeks for PUVA, UVB therapy and topical corticosteroids

• 6 weeks for systemic corticosteroids

• 8 weeks for systemic and topical retinoids

Baseline characteristics

• Age (years, mean (range)): 50 (17 to 90)

• Females N (%): 43 (54)

• Global Severity Score (GSS), mean ± SD: A: 8.1 ± 2.2, B: 7.7 ± 2.1 ⇒ matched with TSS

Interventions

A: betamethasone valerate 0.12%, once daily for 4 weeks (N = 46 participants)

B: betamethasone valerate 0.12%, twice daily for 4 weeks (N = 33 participants)

Outcomes

1. GSS (week 4)

2. Investigator's global assessment of response (week 4) ⇒ matched with IGA

3. Patient's global assessment of response (week 4) ⇒ matched with PGA

4. Erythema (week 4)

5. Thickness (week 4)

6. Scaling (week 4)

Definition:

Investigator’s and patients’ global assessment of response (0 to 6): 0 = completely clear, 1= almost clear, 2 = marked improvement, 3 = moderate improvement, 4 = slight improvement, 5 = no change, 6 = worse

GSS (0 to 12): sum of scores of erythema, thickness and scaling

Erythema (0 to 4): 0 = no erythema, 1 = faint erythema, pink to very light red, 2 = definite light red erythema, 3 = dark red erythema, 4 = very dark red “beefy” erythema

Thickness (0 to 4): 0 = no plaque elevation, 1 = slight, barely perceptible elevation, 2 = definite elevation but not thick, 3 = definite elevation, thick plaque with sharp edge, 4 = very thick plaque with sharp edge

Scaling (0 to 4): 0 = no scaling, 1 = sparse fine scale lesions, 2 = coarser scales, most of lesions covered, 3 = entire lesion covered with coarse scales, 4 = very thick coarse scales, possibly fissured

Visits: baseline and week 4

Notes

—

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote (page 387): "Subjects were randomly assigned to either the qd or the bid dosing group by the study coordinator at each site [...]"

Comment: insufficient detail was reported about the method used to generate the allocation sequence

Allocation concealment (selection bias)

Unclear risk

This was not stated

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Quote (page 388): "The results were analysed on the basis of intention‐to‐treat [...]"

Comment: no information about imputation method used (6 drop‐outs). No information about the distribution of the drop‐outs across groups. However, all randomised patients included for analysis.

Selective reporting (reporting bias)

Low risk

All reported results were pre‐specified outcomes in the methods section

Other bias

High risk

Slightly different values for erythema and plaque thickness scores reported in text and table 3 (i.e. erythema score: initial mean: 2.7 ± 0.8 (text) versus 2.7 ± 0.7 (table 3))

Inclusion criteria: at least 18 years, but age at baseline ranged from 17 to 90 years

Comment: these findings are not considered to have a significant impact on outcomes

Quote (page 388): "The subject and the investigator graded the global response at the follow up visit."

Comment: no baseline IGA and PGA assessed, thus change in these scores not evaluable

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Quote (page 387): "single‐blind study"

Quote (page 388): "The subjects self‐administered the treatment to the entire scalp under the instruction of the study personnel [...]"

Comment: insufficient information about which side was blinded

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Quote (page 387): "single‐blind study"

Quote (page 387): "The physician‐grader performing the evaluations was blinded to the assignment."

Comment: insufficient information about method used to ensure blinding of outcome assessor

Methods

This was a multicentre, randomised, double‐blind, vehicle‐controlled, parallel‐group trial

Participants

Inclusion criteria of the trial

• At least 12 years of age

• Plaque‐type psoriasis involving 3% to 10% of total body surface area (BSA), (excluding the scalp) with Investigator's Static Global Assessment (ISGA) of at least 3

• Target lesion of greater than 2 cm² on trunk or extremities with a score of at least 2 on the psoriasis grading scale

• Psoriasis involving at least 10% of the scalp and ISGA of at least 3

• Negative urine pregnancy test and adequate contraception for female participants

Exclusion criteria of the trial

• Participation in a previous study regarding calcipotriene foam

• Concomitant non‐biologic, antipsoriatic treatment

• Recent treatment with topicals with beneficial effect on psoriasis (including biologics)

• History of immunocompromising disease

Washout period

This was not stated

Baseline characteristics

• Age (years, mean ± SD): A: 45.9 ± 15.3, B: 44.4 ± 15.5

• Females N (%): A: 69 (38), B: 76 (42)

• Scalp area affected (%, mean ± SD): A: 34.2 ± 25.6, B: 32.0 ± 25.7

Interventions

A: calcipotriene foam 0.005%, twice daily for 8 weeks (N = 181 participants)

B: placebo vehicle foam, twice daily for 8 weeks (N = 182 participants)

Outcomes

Primary outcome

1. Scalp ISGA of 0 to 1 (week 8) ⇒ matched with IGA

Secondary outcomes

1. Body ISGA of 0 to 1 (week 2, 4 and 8)

2. Scalp ISGA of 0 to 1 (week 2 and 4) ⇒ matched with IGA

3. Erythema score of 0 to 1 (week 2, 4 and 8)

4. Scaling score of 0 to 1 (week 2, 4 and 8)

5. Thickness score of 0 to 1 (week 2, 4 and 8)

6. Mean percent reductions in percent BSA of body (week 2, 4 and 8)

7. Mean percent reductions in percent BSA of scalp (week 2, 4 and 8)

8. Adverse events (AE) (week 8)

9. Number of patients with at least 1 AE (week 8)

10. Withdrawal due to AE (week 8)

11. Target lesion score (weeks 2 and 4)

Definition:

Scalp ISGA (0 to 5): 0 = clear, 5 = very severe

Erythema, thickness, scaling score (0 to 5, respectively): 0 = clear, 5 = very severe

Target lesion score: sum of erythema, thickness, scaling scores

Visits: baseline, week 1, 2, 4 and 8

Notes

This trial was supported by Stiefel, a GSK company, Research Triangle Park, NC

NCT01139580

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote (page 301): " Subjects were allocated [...] using a 1:1 randomization schedule generated before the study."

Comment: insufficient detail was reported about the method used to generate the allocation sequence

Allocation concealment (selection bias)

Unclear risk

This was not stated

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Quote (page 301): "All analysis were on the ITT population [...] a last‐observation‐carried‐forward (LOCF) method was used"

Comment: missing data sufficiently addressed

Selective reporting (reporting bias)

Low risk

All results were pre‐specified outcomes in the methods section

Other bias

Low risk

No other source of bias identified

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quote (page 301): "Canister were labelled identically", "Study group allocation was unblinded to study personnel after all data were collected and validated [...]"

Comment: probably sufficient

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Quote (page 301): "Canister were labelled identically", "Study group allocation was unblinded to study personnel after all data were collected and validated [...]"

Comment: probably sufficient

Methods

This was a multicentre, randomised, double‐blind, active‐ and vehicle‐controlled trial

Participants

Inclusion criteria of the trial

• Adult patients

• At least 10% of scalp surface involved

• Psoriasis sign score of at least 6 (at least 2 points for erythema, thickness, scaling, respectively)

Exclusion criteria of the trial

• Systemic antipsoriatic therapy within 4 weeks prior to the trial

• Topical therapy on the scalp within 2 weeks prior to the trial

Washout period

This was not stated

Baseline characteristics

• Age (years, mean): A: 46.6, B: 48.6, C: 50.8, D: 48.5

• Females N (%): A: 32 (56), B: 26 (45), C: 14 (50), D: 15 (52)

• Total sign score (TSS) (mean): A: 7.87, B: 7.7, C: 8.33, D: 8.08 ⇒ calculated by review author

Interventions

A: betamethasone valerate foam 0.1%, twice daily for 4 weeks (N = 57 participants)

B: betamethasone valerate lotion 0.1%, twice daily for 4 weeks (N = 58 participants)

C: placebo foam, twice daily for 4 weeks (N = 28 participants)

D: placebo lotion, twice daily for 4 weeks (N = 29 participants)

Outcomes

1. Scaling (week 2 and 4)

2. Erythema (week 2 and 4)

3. Thickness (week 2 and 4)

4. Pruritus (week 2 and 4)

5. TSS (week 2 and 4) ⇒ calculated by review author

6. Investigator's Global Assessment (IGA) (week 4)

7. Patient's Global Assessment (PGA) (week 4)

8. Adverse events (AE) (week 4)

9. Withdrawal due to AE (week 4)

Definition:

IGA /PGA (7‐point scale): lesions rated as completely clear, almost clear (= 'very mild'), marked improvement, moderate improvement, slight improvement, no change, worse

Erythema, thickness, pruritus and scaling score (0 to 4, respectively): 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe

Visits: baseline, week 2 and 4

Notes

This trial was funded by Connetics Corporation, Palo Alto, California

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote (page 629): "[...] randomly assigned to one of four treatment groups in a 2 : 1 : 2 : 1 ratio [...]"

Comment: insufficient detail was reported about the method used to generate the allocation sequence

Allocation concealment (selection bias)

Unclear risk

This was not stated

Incomplete outcome data (attrition bias)
All outcomes

High risk

Quote (page 631): "One hundred and seventy‐two patients (85 men, 87 women), from a total of 190 enrolled, completed the safety and efficacy study."

Comment: insufficient reporting of reasons for attrition or exclusions

Selective reporting (reporting bias)

Low risk

All reported results were pre‐specified outcomes in the methods section

Other bias

Low risk

No other source of bias identified

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Quote (page 629): "double‐blind study"

Comment: insufficient information about how participants and personnel were blinded regarding difference between the 2 vehicles used

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Quote (page 629): "double‐blind study"

Comment: insufficient information about how blinding of outcome assessors was ensured throughout the study

Methods

This was a multicentre, randomised, double‐blind, active‐ and vehicle‐controlled trial

Participants

Inclusion criteria of the trial

• Adult patients

• At least 10% of scalp surface involved

• Psoriasis sign score of at least 6 (at least 2 points for erythema, thickness, scaling, respectively)

Exclusion criteria of the trial

• Other treatment

Washout period

This was not stated

Baseline characteristics

• Females N (%): 95 (50.5)

• Total sign score (TSS): A: 7.28, B: 7.43, C: 9.94, D: 7.00 ⇒ calculated by review authors

Interventions

A: clobetasol propionate (CP) foam 0.05%, twice daily for 14 days (N = 62 participants)

B: CP solution 0.05%, twice daily for 14 days (N = 63 participants)

C: placebo foam, twice daily for 14 days (N = 31 participants)

D: placebo solution, twice daily for 14 days (N = 32 participants)

Assignment in a 2:1:2:1 ratio: CP foam:placebo foam:CP solution:placebo solution

Outcomes

1. Scaling (week 1, 2 and 4)

2. Erythema (week 1, 2 and 4)

3. Plaque thickness (week 1, 2 and 4)

4. Pruritus (week 1, 2 and 4)

5. Investigator's Global Assessment (IGA) (week 2 and 4)

6. Patient's Global Assessment (PGA) (week 2 and 4)

7. Adverse events (AE) (week 4)

Definition:

IGA/PGA (7‐point scale): lesions rated as completely clear, almost clear (= 'very mild'), marked improvement, moderate improvement, slight improvement, no change, or worse

Erythema, thickness, pruritus and scaling score (0 to 4, respectively): 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe

Visits: baseline, week 1, 2 and 4 (follow‐up)

Notes

Funded by Connetics Corporation, Palo Alto, CA, USA

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Insufficient detail was reported about the method used to generate the allocation sequence

Allocation concealment (selection bias)

Unclear risk

This was not stated

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Quote (page 536): "All enrolled subjects [...] successfully completed the study."

Comment: no missing outcome data

Selective reporting (reporting bias)

High risk

Quote (page 537): "The percentage of patients reporting adverse events and the incidence of adverse events judged as being related to study medication did not differ significantly among the treatment groups."

Comment: insufficient data regarding the incidence or characteristics of adverse events reported

Other bias

High risk

Baseline characteristics (TSS, calculated by review authors) not balanced between groups

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Quote (page 535): "double‐blind"

Comment: insufficient information about how participants and personnel were blinded regarding difference between the 2 vehicles used

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Quote (page 535): "double‐blind"

Comment: insufficient information about how blinding of outcome assessors was ensured throughout the study

Methods

This was a randomised, double‐blind, active‐controlled trial

Participants

Inclusion criteria of the trial

• Patients with psoriasis of the scalp

Exclusion criteria of the trial

• Tuberculosis of the skin

• Viral infections with skin lesions

• Pregnant or breastfeeding women

• No dressings were allowed and no concomitant treatment with topical or systemic corticosteroids, antihistamines or vasoconstrictor

Washout period

This was not stated

Baseline characteristics

• Age (years, range): 18 to 64

• Females N (%): 33 (37)

Interventions

A: betamethasone 17,21‐dipropionate 0.05% in alcoholic solution, twice daily for 4 weeks (N = 29 participants)

B: betamethasone 17,21‐dipropionate 0.05% plus salicylic acid 2.0% in alcoholic solution, twice daily for 4 weeks (N = 30 participants)

C: triamcinolone acetonide 0.2% plus salicylic acid 2.0% in alcoholic solution, twice daily for 4 weeks (N = 31 participants)

Outcomes

1. Induration (week 2 and 4)

2. Lichenification (week 2 and 4)

3. Excoriation (week 2 and 4)

4. Inflammation (week 2 and 4)

5. Crusting (week 2 and 4)

6. Scaling (week 2 and 4)

7. Pruritus (week 2 and 4)

8. Pain (week 2 and 4)

9. Physician's overall evaluation (week 2 and 4) ⇒ 'cured' matched with IGA = 'clear'

Definition:

Outcomes 1 to 8: each rated on a score from 0 to 3: 0 = absence, 1 = mild, 2 = moderate, 3 = severe

Physician's overall evaluation: clinical cure = complete remission, clinical improvement = marked (> 70% but < 100%), moderate (>30% but < 70%), slight (< 30%), treatment failure = no change or worsening

Visits: baseline, week 2 and 4

Notes

—

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote (page 253): "patients were allocated one of the preparations at random"

Comment: insufficient detail was reported about the method used to generate the allocation sequence

Allocation concealment (selection bias)

Unclear risk

This was not stated

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Quote (page 253): "All patients completed the trial period."

Comment: data for each outcome completely addressed

Selective reporting (reporting bias)

High risk

Quote (page 253): "There was no statistically significant difference regarding the variables lichenification, excoriation, crusting, scaling, pruritus and pain [...] were present to too small a degree to make an analysis meaningful"

Comment: some results were not reported. No baseline data for each specific group reported. No baseline severity as inclusion criteria defined.

Other bias

Low risk

No other source of bias identified

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quote (page 253): "identical plastic bottles bearing only a patient number [...] choice remaining unknown to the investigator and to the patient until the code was broken at the end of the trial"

Comment: probably sufficient

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Quote (page 253): "identical plastic bottles bearing only a patient number [...] choice remaining unknown to the investigator and to the patient until the code was broken at the end of the trial"

Comment: probably sufficient

Methods

This was a randomised, double‐blind, active‐controlled, parallel‐group trial

Participants

Inclusion criteria of the trial

• Patients with psoriasis of the scalp

Exclusion criteria of the trial

This was not stated

Washout period

This was not stated

Baseline characteristics

• Females N (%): A: 11 (55), B: 16 (80)

• Age (years, mean ± SD): A: 41.0 ± 18.1, B: 40.7 ± 16.5

• Desquamation score (mean): A: 4.1, B: 4.1

• Excoriation (mean): A: 2.7, B: 2.8

• Infiltration (mean): A: 4.1, B: 4.0

Interventions

A: hydrocortisone 17‐butyrate 0.1% cream, once daily for 4 weeks (N = 20 participants)

B: fluocinolone acetonide 0.025% cream, once daily for 4 weeks (N = 20 participants)

Outcomes

1. Desquamation (week 1, 2, 3 and 4)

2. Excoriation (week 1, 2, 3 and 4)

3. Infiltration (week 1, 2, 3 and 4)

4. Clearance (week 1, 2, 3 and 4) ⇒ matched with IGA: 'clear'

5. Number of patients with at least one adverse event (AE) (week 4)

Definition:

Desquamation, excoriation score (1 to 5, respectively): 1 = none, 5 = very severe

Infiltration score: 5 = severe, 4 = moderate, 3 = slight, 2 = erythema only, 1 = normal skin alone

Visits: baseline, week 1, 2, 3 and 4

Notes

—

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote (page 198): "[...] 40 patients with psoriasis of the scalp were randomly allocated to one of 2 groups."

Comment: insufficient detail was reported about the method used to generate the allocation sequence

Allocation concealment (selection bias)

Unclear risk

This was not stated

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All outcome data complete

Selective reporting (reporting bias)

Low risk

All reported results were pre‐specified outcomes in the methods section

Other bias

Low risk

No other source of bias identified

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Quote (page 198): "double‐blind study"

Comment: insufficient detail was reported about the method used to blind study participants or personnel from the intervention a participant received

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Quote (page 198): "double‐blind study"

Comment: insufficient detail was reported about the method used to blind assessor from the intervention a participant received

Methods

This was a multicentre, prospective, randomised, double‐blind, placebo‐controlled, parallel‐group trial

Participants

Inclusion criteria of the trial

• Adults with diagnosis of mild to moderate scalp psoriasis

Exclusion criteria of the trial

• Excessively thick scalp psoriasis

• Other dermatological disease of the scalp

• Marked deterioration of scalp psoriasis at study entry

• Concomitant therapy with potent topical corticosteroids, vitamin D or calcium supplements

• Other medication (including lithium and beta‐blockers) that could interfere with the course of the disease

• Conditions such as hypercalcaemia, hepatic or renal disease at entry of study

• Women with child‐bearing potential with inappropriate contraception

Washout period

• 2 weeks: only non‐medicated shampoo was allowed

• 2 months: systemic antipsoriatic therapy (including phototherapy)

Baseline characteristics

• Total sign score (TSS), mean: A: 6.75, B: 6.55 (data out of graph)

Interventions

A: calcipotriol solution 50 µg/ml, twice daily for 4 weeks (N = 25 participants)

B: placebo vehicle, twice daily for 4 weeks (N = 24 participants)

Outcomes

1. TSS (week 1, 2 and 4)

2. Extent of scalp psoriasis (week 1, 2 and 4)

3. Redness (week 1, 2 and 4)

4. Thickness (week 1, 2 and 4)

5. Scaliness (week 1, 2 and 4)

6. Flaking (weeks 1, 2 and 4)

7. Pruritus (weeks 1, 2 and 4)

8. Patient's overall assessment of treatment response (POA) (weeks 1, 2 and 4)

9. Investigator's overall assessment of treatment response (IOA) (weeks 1, 2 and 4)

10. Patient assessment of flaking and itching (weeks 1, 2 and 4)

11. Number of patients with at least one adverse event (AE) (week 4)

12. Withdrawal due to AE (week 4)

13. Compliance (week 4)

14. Withdrawal due to treatment failure (week 4)

15. Changes in blood work (week 4)

Definition:

Redness, scaliness and thickness, pruritus, flaking score (0 to 4): 0 = absent, 1 = slight, 2 = moderate, 3 = severe, 4 = severest possible

Extent of scalp psoriasis (0 to 5): 0 = no involvement, 1 = < 20%, 2 = 20% to 39%, 3 = 40% to 59%, 4 = 60% to 79%, 5 = 80% to 100%

IOA/POA (‐1 to 3): ‐1 = worse, 0 = no change, 1 = slight improvement, 2 = marked improvement, 3 = cleared (matched with IGA/PGA = clear)

Blood work: haematology and biochemistry (including serum total calcium, hepatic and renal parameters)

TSS (0 to 12): sum of the 3 parameters thickness, redness and scaliness

Visits: baseline, week 1, 2 and 4

Notes

This study was sponsored by Leo Pharmaceutical Products, Ballerup, Denmark

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote (page 483): "[...] patients were randomly allocated to receive either calcipotriol solution (50 /ig/ml) or placebo [...]"

Comment: insufficient detail was reported about the method used to generate the allocation sequence

Allocation concealment (selection bias)

Unclear risk

This was not stated

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Quote (page 486): "Forty‐six of the 49 patients completed the study‐one in the active group withdrew because of local side‐effects [...] two in the placebo group withdrew because of an inadequate treatment response."

Comment: no ITT analysis used, but all outcomes except for TSS with ITT population reported. No imputation method reported.

Selective reporting (reporting bias)

Low risk

All results were pre‐specified outcomes in the methods section

Other bias

Low risk

No other source of bias identified

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quote (page 483‐4): "The active and placebo preparations [...] were similar in appearance, smell, and texture, and supplied in identical packaging."

Comment: blinding probably sufficient

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Quote (page 483‐4): "The active and placebo preparations [...] were similar in appearance, smell, and texture, and supplied in identical packaging."

Comment: blinding probably sufficient

Methods

This was a 4‐week, multicentre, randomised, parallel‐group, investigator‐masked trial

Participants

Inclusion criteria of the trial

• Adults (at least 18 years) with diagnosis of mild to moderate scalp psoriasis

• At least 15% psoriatic scalp involvement

Exclusion criteria of the trial

• Pregnant or breastfeeding women

• Immunocompromised patients

• Patients with known allergy or contraindications to the studied medications

• Concomitant systemic anti‐psoriatic medications

• Concomitant medication with potential to aggravate the course of the disease

Washout period

• Quote (page 91): "[...] specified washout periods for systemic therapies [...]"

Baseline characteristics

• Total sign score (TSS), mean: A: 6.1, B: 6.2 (data out of graph)

• Age (years, mean ± SD): A: 46 ± 14.9, B: 45.4 ± 13.2

• Females N (%): A: 62 (51.2), B: 14 (34.1)

Interventions

A: clobetasol propionate 0.05% shampoo, once daily for 4 weeks (N = 121 participants)

B: tar blend 1% shampoo, twice daily for 4 weeks (N = 41 participants)

Allocation was done in a 3:1 (A:B) ratio

Outcomes

Primary outcomes of the trial

1. Total severity score (TSS) (week 2 and 4)

2. Global severity score (GSS) (week 2 and 4)

Secondary outcomes of the trial

1. Erythema (week 2 and 4)

2. Thickness (week 2 and 4)

3. Desquamation (week 2 and 4)

4. Pruritus (week 2 and 4)

5. Participants' global assessment of improvement (week 2 and 4) ⇒ matched with PGA

6. Percentage of scalp involvement (week 2 and 4)

7. Cutaneous safety (week 2 and 4)

8. Number of patients with at least 1 adverse event (AE) (week 4)

9. Withdrawal due to AE (week 4)

10. Ocular safety (week 2 and 4)

11. Cosmetic acceptability (week 4)

Definition:

TSS (0 to 9): sum of scores for erythema, desquamation and plaque thickening

GSS (0 to 5): 0 = none ‐ 5 = very severe

Erythema, desquamation and thickness, pruritus score (0 to 3): 0 = absent ‐ 3 = severe

Subject's global assessment of improvement: (‐1 to 5): ‐1 = worse to 5 = clear

Cutaneous safety: 0 = none to 3 = severe for telangiectasia, skin atrophy and burning, respectively

Ocular safety: 0 = none to 3 = severe

Cosmetic acceptability: questionnaire at the end of the trial with 12 items

Visits: baseline, week 2 and 4

Notes

Galderma Medical Affairs assisted in writing the article

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote (page 91): "Subjects were randomized at baseline to either clobetasol propionate 0.05% shampoo or to tar blend 1% shampoo in a ratio of 3:1."

Comment: insufficient detail was reported about the method used to generate the allocation sequence

Allocation concealment (selection bias)

Unclear risk

This was not stated

Incomplete outcome data (attrition bias)
All outcomes

Low risk

"All efficacy parameters, with the exception of the subject’s assessment of global improvement, were analysed at the last visit (ITT analysis) or at the week visit (PP analysis) using an analysis of covariance (ANCOVA), using the baseline variable as a covariate and centre and treatment as factors."

Comment: incomplete outcome data sufficiently addressed

Selective reporting (reporting bias)

Low risk

All reported results were pre‐specified outcomes in the methods section

Other bias

Low risk

No other source of bias identified

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Quote (91): "[...] investigator‐masked [...]"

Comment: no blinding of participants or personnel done

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Quote (page 91): "The investigator was masked to the treatment allocation."

Comment: blinding of outcome assessment insufficiently reported

Methods

This was a multicentre, randomised, parallel‐group, double‐blind trial

Participants

Inclusion criteria of the trial

• Patients with diagnosis of scalp psoriasis

Exclusion criteria of the trial

• Concomitant treatment with any other topical or systemic corticosteroid, antibiotic or antihistamine

Washout period

This was not stated

Baseline characteristics

• Females N (%): 36 (46)

• Number of patients (%) with severe scaling: A: 23 (62), B: 19 (58)

Interventions

A: micronized betamethasone 17‐valerate 0.1% in isopropyl alcohol lotion, twice daily for 2 weeks (N = 45 participants)

B: vehicle, twice daily for 2 weeks (N = 33 participants)

Outcomes

1. Clinical response (day 5, 8, 14)

2. Lichenification (day 14)

3. Excoriation (day 14)

4. Inflammation (including degree of inflammation) (day 14)

5. Crusting (day 14)

6. Scaling (day 14)

7. Vesiculation (day 14)

8. Exudation (day 14)

9. Fissures (day 14)

10. Maceration (day 14)

11. Pruritus (day 14)

12. Burning (day 14)

13. Pain (day 14)

14. Secondary bacterial infection (day 14)

15. Adverse events (AE) (day 14)

16. Withdrawal due to treatment failure (day 14)

Definition:

Patient's clinical response: rated on a score from 1 to 6: 1 = no evaluation, 2 = exacerbation, 3 = poor or no effect, 4 = fair, partial clinical control of condition (less than 50%), 5 = good, moderate clinical control of condition (50% to 75%), 6 = excellent, complete clinical control of condition (75% or more) (matched with IGA = responder)

Outcomes 2 to 14: graded on a score from 1 to 4: 1 = none, 2 = slight, 3 = moderate, 4 = severe

Visits: baseline, day 5, 8 and 14

Notes

The study investigated 2 groups separately: patients with seborrhoeic dermatitis and patients with psoriasis of the scalp

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote (page 640): "[...] according to a randomized code."

Comment: insufficient detail was reported about the method used to generate the allocation sequence

Allocation concealment (selection bias)

Low risk

Quote (page 393): "The test preparations ware supplied to each investigator in identical packages, code labelled for blind randomized assignment to patients. [...] Master codes for each study were maintained separately from the investigators"

Comment: probably sufficient

Incomplete outcome data (attrition bias)
All outcomes

High risk

Quote (page 642): "Of the 95 psoriasis patients entered into the eleven studies, 5 did not return for further follow‐up after the initial visit, and 12 were excluded for the following reasons: 9 used a concomitant medicated shampoo and 3 used a concomitant corticosteroid."

Comment: no ITT, but per‐protocol analysis performed

Selective reporting (reporting bias)

Low risk

All reported results were pre‐specified outcomes in the methods section

Other bias

High risk

Quote (page 340): "The majority of the patients were placed on a bid basis."

Comment: insufficient information about how many and why participants were placed on bid or opd basis. Performance bias possible.

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quote (page 639): "They compared a betamethasone valerate lotion and a placebo (the lotion vehicle) [...]"

Quote (page 640): "Neither patient nor physician was aware of which of the two was being used."

Comment: probably sufficient blinding performed

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Quote (page 639‐40): "The test preparations ware supplied to each investigator in identical packages, code labelled for blind randomized assignment to patients [...] "

Quote (page 639): "They compared a betamethasone valerate lotion and a placebo (the lotion vehicle) [...]"

Quote (page 640): "Neither patient nor physician was aware of which of the two was being used."

Comment: probably sufficient blinding performed

Methods

This was a randomised, parallel‐group trial

Participants

Inclusion criteria of the trial

• Plaque psoriasis of the head and face

Exclusion criteria of the trial

• Need for systematic antipsoriatic treatment

• Any other skin disease in the region of psoriasis lesions

• Pregnant or breastfeeding women

• Severe conditions of the heart, liver or kidney

• Weakened immune system

Washout period

• Within 2 weeks to randomisation: glucocorticoids or other topical treatment

• Within 4 weeks to randomisation: any therapy for psoriasis or immunosuppressants

Baseline characteristics

• Females N (%): 19 (47.5)

• Age (years, mean (range)): 41.5 (18 to 65)

• Total sign score (TSS): A: 8.90, B: 9.56 ⇒ TSS was calculated by the review author

Interventions

A: tacrolimus 0.1% ointment, twice daily for 8 weeks (N = 20 participants)

B: pine tar 5% ointment, twice daily for 8 weeks (N = 20 participants)

Outcomes

1. Dander (week 2, 4, 6 and 8)

2. Erythema (week 2, 4, 6 and 8)

3. Pruritus (week 2, 4, 6 and 8)

4. Thickness/infiltration (week 2, 4, 6 and 8)

5. Severity score of sign symptoms ⇒ matched with TSS

6. Area score (week 2, 4, 6 and 8)

7. Cure rate (week 2, 4, 6 and 8) ⇒ matched with IGA = 'clear'

8. Response rate (week 2, 4, 6 and 8)

9. Adverse events (AE) (week 8)

Definition:

Cure rate: percent of patients with the change ratio of an area score of 100%

Response rate: percent of patients with the change ratio of an area score of 75%

Area score: 5‐point score: 0 = psoriasis completely improved, 1 = 75% to 90% improvement, 2 = 50% to 74% improvement, 3 = 25% to 49% improvement, 4 = < 25% improvement

Severity score of sign symptoms (0 to 16): sum of dander, erythema, pruritus, thickness/infiltration scores

Dander, erythema, pruritus, thickness/infiltration scores: each rated on a scale from 0 = none to 4 = very severe

Visits: baseline, week 2, 4, 6 and 8

Notes

This article was translated by Mrs. Sai Zhao of Systematic Review Solutions Ltd, China

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote (page 254, abstract): "patients were randomly assigned"

Comment: insufficient detail was reported about the method used to generate the allocation sequence. No further information in the article found by the translator.

Allocation concealment (selection bias)

Unclear risk

This was not stated

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No ITT analysis reported, but data for all randomised participants provided

Selective reporting (reporting bias)

Low risk

All reported results were pre‐specified outcomes in the methods section

Other bias

Low risk

No other source of bias identified

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

This was not stated

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

This was not stated

Methods

This was a randomised, double‐blind, parallel‐group trial

Participants

Inclusion criteria of the trial

• Patients with diagnosis of scalp psoriasis

Exclusion criteria of the trial

• Infection (viral or microbial) of the skin

• Pregnant or breastfeeding women

• Concomitant medication with interfering potential to the course of disease

Washout period

This was not stated

Baseline characteristics

This was not stated

Interventions

A: betamethasone 17,21‐dipropionate solution plus salicylic acid in 2% alcoholic solution, twice daily for 3 weeks (N = 39 participants)

B: betamethasone valerate solution, twice daily for 3 weeks (N = 39 participants)

Outcomes

1. Overall treatment response (week 1, 2 and 3) ⇒ matched with IGA: 'clear'

2. Adverse events (AE) (week 3)

3. Number of patients with at least 1 AE (week 3)

4. Cosmetic acceptability (week 3)

Definition:

Overall treatment response (6‐point scale): graded as 'cure', 'marked improvement' (> 70%), 'moderate improvement' (30% to 70%), 'slight improvement' (≤ 30%), 'no change' or 'worse'

Visits: baseline, week 1, 2 and 3

Notes

—

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote (page 48): "The patients were randomly allocated to one of the two groups [...]"

Comment: insufficient detail was reported about the method used to generate the allocation sequence

Allocation concealment (selection bias)

Unclear risk

This was not stated

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Quote (page 49, Table III): "*patient No. 8 not evaluated" (for week 2), "**patient No. 72 not evaluated" (for week 3)

No ITT analysis performed, but influence on outcome data not considered as significant

Selective reporting (reporting bias)

Low risk

All results were pre‐specified outcomes in the methods section

Other bias

Low risk

No other source of bias identified

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quote (page 48): "The bottles looked identical. Neither staff nor patients knew who received which treatment until the trial was finished."

Comment: blinding probably sufficient

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Quote (page 48): "The bottles looked identical. Neither staff nor patients knew who received which treatment until the trial was finished."

Comment: blinding probably sufficient

Methods

This was a randomised, double‐blind, parallel‐group trial

Participants

Inclusion criteria of the trial

• Patients with diagnosis of scalp psoriasis

Exclusion criteria of the trial

• Infection of the skin (microbial or viral)

• Pregnant women

• Concomitant medication with interfering potential

Washout period

This was not stated

Baseline characteristics

• Data only for 51/53 randomised patients reported

• Age (years, mean): 36

• Females N (%): 28 (54.9)

Interventions

A: betamethasone 17, 21‐dipropionate plus salicylic acid 2% alcoholic solution, twice daily for 3 weeks (N = 25 participants)

B: clobetasol propionate lotion, twice daily for 3 weeks (N = 25 participants)

Participants could withdraw prior to week 3 if healing occurred

Outcomes

1. Induration (week 1, 2 and 3)

2. Lichenification (week 1, 2 and 3)

3. Crusting (week 1, 2 and 3)

4. Pruritus (week 1, 2 and 3)

5. Scaling (week 1, 2 and 3)

6. Pain (week 1, 2 and 3)

7. Investigator's overall evaluation (week 1, 2 and 3) ⇒ 'cure' matched with IGA: 'clear'

8. Adverse events (AE) (week 3)

9. Number of patients with at least 1 AE (week 3)

10. Withdrawal due to AE (week 3)

11. Cortisol blood level (day ‐1, 3, 7, 14 and 21)

Definition:

Investigator's overall evaluation: patient's response from initial state rated as 'cure' = complete remission of signs and symptoms, 'marked improvement' = ≥ 70%, 'moderate improvement' = 30% to 70%, 'slight improvement' = ≤ 30%, 'failure' = no change or worse

Visits: baseline, week 1, 2 and 3

Notes

—

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote (page 419): "patients were randomly allocated."

Comment: insufficient detail was reported about the method used to generate the allocation sequence

Allocation concealment (selection bias)

Unclear risk

This was not stated

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Quote (page 419): "Two of the patients did not return at the follow‐up visits. The remaining fifty‐one patients [...] did not show any treatment group differences"

Quote: (page 420): "One patient [...] has been excluded from the evaluation of efficacy due to concomitant therapy with methotrexate."

Quote (page 420): "In the Dermovate group [...] three were treatment failure and two drop‐outs"

Comment: no ITT analysis and no adequate imputation method performed. Insufficient reporting about reasons for drop‐out. However, attrition considered too small (< 10%) to have a relevant impact on outcome.

Selective reporting (reporting bias)

High risk

Quote (page 420): "Pruritus [...] was the only symptom showing a statistically significant difference"

Comment: insufficient reporting of this outcome. In addition, no data for other pre‐specified outcomes (induration, lichenification, crusting, pain, scaling) reported.

Other bias

Unclear risk

Selection criteria for patients of which the blood cortisol level was assessed unclear. Selection bias possible.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Quote (page 419): "using a double‐blind technique"

Comment: insufficient detail was reported about the method used to blind study participants or personnel from the intervention a participant received

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Quote (page 419): "using a double‐blind technique"

Comment: insufficient detail was reported about the method used to blind the outcome assessor from the intervention a participant received

Methods

This was a randomised, double‐blind, parallel‐group trial

Participants

Inclusion criteria of the trial

• Patients with diagnosis of scalp psoriasis

Exclusion criteria of the trial

• Patients treated with other corticosteroids 1 week prior to the study

• Infection of the skin

• Pregnant or breastfeeding women

• Concomitant medication with interfering potential

Washout period

This was not stated

Baseline characteristics

• Total sign score (TSS), mean: A: 7.15, B: 7.4 ⇒ calculated by review author

• Females N (%): 24 (60)

Interventions

A: desoximethasone solution 0.25% plus salicylic acid 1%, twice daily for 2 weeks (N = 20 participants)

B: betamethasone valerate solution 0.1%, twice daily for 2 weeks (N = 20 participants)

Outcomes

1. Degree of severity (week 1, 2 and 3) ⇒ matched with TSS

2. Erythema (week 1, 2 and 3)

3. Infiltration (week 1, 2 and 3)

4. Pruritus (week 1, 2 and 3)

5. Scaling (week 1, 2 and 3)

6. Patient's overall evaluation (week 1, 2 and 3)

7. Investigator's overall evaluation (week 1, 2 and 3)

8. Adverse events (week 1, 2 and 3)

9. Cosmetic acceptability (week 1, 2 and 3)

10. Withdrawal due to treatment failure (week 3)

Definition:

Outcomes 1 to 4.: each graded on a score from 0 to 3: 0 = none, 1 = slight, 2 = moderate, 3 = severe

Degree of severity (0 to 12): sum of erythema, scaling, infiltration and pruritus

Patient's and investigator's overall evaluation: results rated as 'much better', 'slightly better', 'no change', 'slightly worse', 'much worse'

Cosmetic acceptability: results rated by the patient as 'very good', 'good', 'moderate', 'poor', 'no answer'

Visits: baseline, week 1, 2 and 3 (follow‐up)

Notes

—

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote (page 171): "The randomization was done in advance by the manufacturer with the aid of a table with random digits and kept secret from the doctor during the study."

Comment: probably sufficient sequent generation

Allocation concealment (selection bias)

Low risk

Quote (page 171): "The randomization was done in advance by the manufacturer with the aid of a table with random digits and kept secret from the doctor during the study."

Comment: probably sufficient

Incomplete outcome data (attrition bias)
All outcomes

High risk

Quote (page 172, Table 1): "Two patients are not included because they were treatment failures after the first week of treatment."

Comment: no ITT analysis and no adequate imputation method performed

Selective reporting (reporting bias)

Low risk

All results were pre‐specified outcomes in the methods section

Other bias

Low risk

No other source of bias identified

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Quote (page 171): "50ml bottle with identical appearance. [...] the two solutions differed in odour [...]"

Comment: unclear if odour could affect outcome

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Quote (page 171): "50ml bottle with identical appearance. [...] The doctor was informed that the two solutions differed in odour and that he was not allowed to sniff them."

Comment: blinding probably insufficiently ensured

Methods

This was a randomised, single‐blind, parallel‐group trial

Participants

Inclusion criteria of the trial

• Patients with stable or worsening scalp psoriasis

• At least 18 years

• At least 10% of the psoriatic scalp involvement

• Global score of at least 3 and maximum 6

Exclusion criteria of the trial

• Known allergy to topical corticosteroids (including betamethasone)

• Allergy to nuts or peanuts

• Additional non‐psoriatic scalp condition

• Severe or uncontrolled disease (including psoriasis)

• Patients with history of treatment failure with topical corticosteroids within the previous year

• 4 weeks prior to the study: systemic therapy (including corticosteroids, retinoids) or PUVA therapy

• 2 weeks prior to the study: topical therapy (including retinoids, corticosteroids, medicated (e.g. coal tar, zinc, ketoconazole, selenium sulfide) shampoos)

• Inadequate contraception

• Concomitant medication with interfering potential

Washout period

• 2 weeks: topical therapy (see exclusion criteria)

• 4 weeks: systemic therapy (see exclusion criteria)

Baseline characteristics

• Age (years, mean ± SD): 50 ± 14

• Females N (%): 13 (54)

• Total severity score (TSS), mean ± SD: 5.2 ± 1.0

Interventions

A: betamethasone valerate 0.12% foam, twice daily for 2 weeks (N = 13 participants)

B: fluocinolone acetonide 0.01% oil, once daily for 2 weeks (N = 12 participants)

Cross‐over took place after 2 weeks

Outcomes

1. TSS (day 14 and 28)

2. Investigator's assessment of global response (day 14 and 28)

3. Patient's assessment of global response (day 14 and 28)

4. Quality of life (QOL) (day 14 and 28)

5. Treatment preference measure (day 14 and 28)

6. Erythema (day 14 and 28)

7. Thickness (day 14 and 28)

8. Scaling (day 14 and 28)

9. Pruritus (day 14 and 28)

Definition:

TSS: sum of erythema, scaling and thickness score

Outcomes 4 to 7.: each graded on a score from 0 to 4, higher scores indicating worse severity

Patient's and investigator's global response: results rated on a scale from 0 to 6, higher scores indicating worse disease severity

Treatment preference measure (‐21 to +21): for both intervention each characteristic "ease of application", "application time", "absorption", "how it feels to odour", "how it feels on skin" and "how much it stains" were rated by the patient on a scale from ‐3 to 3: ‐3 = extremely unappealing, ‐2 = moderately unappealing, ‐1 = slightly unappealing, 0 = neutral, +1 = slightly appealing, +2 = moderately appealing and +3 = extremely appealing

QOL score: patients graded each intervention on a scale from ‐3 to 3: ‐3 = will greatly worsen quality, ‐2 = will moderately worsen the quality, ‐1 = slightly worsen the quality, 0 = will have no effect, +1 = will slightly improve the quality, +2 = will moderately improve the quality and +3 = will greatly improve the quality

Visits: baseline, day 14 and 28

Notes

This study was supported by Connetics Corporation

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote (page 28): "[...] each patient was randomized [...]"

Comment: insufficient detail was reported about the method used to generate the allocation sequence

Allocation concealment (selection bias)

Unclear risk

Quote (page 28): "The physician‐grader was blinded to treatment‐group assignment."

Comment: insufficient information about how allocation concealment was performed

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Quote (page 29): "Twenty‐four of 25 patients completed the trial (1 patient was lost to follow‐up)."

Comment: no ITT analysis performed, but attrition not considered to have a significant impact on outcome

Selective reporting (reporting bias)

High risk

Quote (page 29): "total severity scores [...] were not significantly different for the medications"

Comment: insufficient reporting of relevant outcomes: TSS, erythema, scaling, thickness, pruritus, investigator's/patient's global assessment of response and QOL score

Quote (page 29): "As a final indication of preference, 18 patients requested prescriptions for particular medications at the conclusion of the study: 11 requested foam, 4 requested oil, and 1 requested both"

Comment: this outcome was not pre‐specified in the methods section

Other bias

Low risk

No other source of bias identified

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Quote (page 27): "[...] single‐blind trial [...]"

Comment: blinding of patients not possible due to physical difference of vehicles (foam versus oil). This might have an impact on subjective outcomes (pruritus, quality of life).

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Quote (page 27): "[...] single‐blind trial [...]"

Comment: insufficient reporting about method of blinding

Methods

This was a randomised, double‐blind, bilateral‐paired comparison (split‐face) trial

Participants

Inclusion criteria of the trial

• Diagnosis of moderate to severe scalp psoriasis

• Presentation of erythema and scaling in target lesions

Exclusion criteria of the trial

This was not stated

Washout period

This was not stated

Baseline characteristics

• Age (years, range): 19 to 78

• Females N (%): 32 (58)

• Pruritus score: 1.8 (data out of graph)

Interventions

A: augmented betamethasone dipropionate 0.05% lotion, once daily for 3 weeks (N = 55 participants)

B: clobetasol propionate 0.05% solution, once daily for 3 weeks (N = 55 participants)

This was a split‐face comparison

Outcomes

1. Degree of change in total severity/sign score (TSS) (day 4, 8, 15 and 22)

2. Global evaluation score (day 4, 8, 15 and 22) ⇒ matched with IGA: 'clear', 'responder'

3. Induration (day 4, 8, 15 and 22)

4. Pruritus score (day 4, 8, 15 and 22)

5. Patient's preference of treatment (day 4, 8, 15 and 22)

6. Cosmetic acceptability (day 4, 8, 15 and 22)

7. Adverse events (AE) (day 22)

Definition:

Degree of change: difference between TSS during treatment and pre‐treatment divided by the TSS at pre‐treatment, multiplied by 100

TSS (0 to 3): sum of erythema, thickness, scaling and pruritus scores

Pruritus score (0 to 3): 0 = none, 1 = mild, 2 = moderate, 3 = severe

Global evaluation score: comparison of the patients' overall disease status at each return visit to their initial baseline condition

Visits: baseline, day 4, 8, 15 and 22

Notes

This was a split‐face comparison

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote (page 105): "Treatment assignment to the right or left side was determined by a random code."

Comment: insufficient detail was reported about the method used to generate the allocation sequence

Allocation concealment (selection bias)

Unclear risk

This was not stated

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Quote (page 107, Table 2): "**Endpoint=the last valid visit, independent of the visit day on which it occurred."

Comment: only for endpoint (day 22) data for the ITT population for efficacy analysis reported using the last observation carried forward (LOCF) imputation method. Other visits: per‐protocol population.

Selective reporting (reporting bias)

Low risk

All results were pre‐specified outcomes in the methods section

Other bias

Low risk

No other source of bias identified

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Quote (page 105): "double‐blind"

Comment: insufficient detail was reported about the method used to blind study participants or personnel

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Quote (page 105): "double‐blind"

Comment: insufficient detail was reported about the method used to blind the outcome assessor

Methods

This was a multicentre, randomised, double‐blind, placebo‐controlled, parallel‐group trial

Participants

Inclusion criteria of the trial

• Global severity score (GSS) of at least 3

• Age of at least 12 years

Exclusion criteria of the trial

• Pregnant, nursing or pregnancy‐planning women

• Patients with known allergy to components of intervention products

• Systemic treatment for scalp psoriasis

• Necessity of concomitant psoriasis therapy

• Excessive UV exposure

Washout period

• Quote (page 368): "[...] specified wash‐out periods for systemic anti‐psoriatic medications."

Baseline characteristics

• Age (years, mean ± SD): A: 45.1 ± 15.28, B: 45.1 ± 15.71

• Females N (%): A: 57 (60), B: 25 (53.2)

• Total severity score (TSS), mean ± SD: A: 6.5 ± 1.06, B: 6.7 ± 1.22

Interventions

A: clobetasol propionate 0.05% shampoo, once daily for 4 weeks (N = 95 participants)

B: vehicle shampoo, once daily for 4 weeks (N = 47 participants)

Assignment in 2:1 (A:B) ratio

Outcomes

Primary outcome of the trial

1. GSS ≤ 1 (week 4)

Secondary outcomes of the trial

1. TSS (week 2, 4, 6)

2. Pruritus (week 2, 4, 6)

3. Erythema (week 2, 4, 6)

4. Scaling (week 2, 4, 6)

5. Induration/thickness of plaques (week 2, 4, 6)

6. Pruritus (week 2, 4, 6)

7. Percentage scalp surface are of involvement (week 4)

8. Investigator's global assessment of improvement (IAGI) (week 4)

9. Patient's global assessment of improvement (PAGI) (week 4)

10. Adverse events (AE) (week 4)

11. Withdrawal due to AE (week 4)

12. Maintenance of GSS less than or equal 1 (week 6)

Definition:

GSS (0 to 5): 0 = clear, 1 = minimal, 2 = mild, 3 = moderate, 4 = severe, 5 = very severe

TSS (0 to 9): sum of erythema, thickness, scaling scores

Outcomes 2 to 5.: each rated on score from 0to 3: 0 = none, 3 = severe

IAGI/PAGI (0to 5): scale from 0 = clear to 5 = very severe (matched with IGA/PGA = responder)

Visits: baseline, week 2, 4 and 6 (follow‐up)

Notes

This study was supported by Galderma R&D Inc.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote (page 368): "computer‐generated randomization list"

Comment: probably adequate sequence generation

Allocation concealment (selection bias)

Unclear risk

This was not stated

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Quote (page 368‐369): "The intent‐to‐treat (ITT) population was primary for the efficacy analysis. [...] with missing data imputed using the last observation carried forward (LOCF) [...]"

Comment: incomplete outcome data sufficiently addressed

Selective reporting (reporting bias)

Low risk

All reported results were pre‐specified outcomes in the methods section

Other bias

Low risk

No other source of bias identified

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

This was a double‐blind trial with vehicle used as control

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

This was a double‐blind trial with vehicle used as control, but insufficient reporting about how blinding of the investigator was performed and maintained

Methods

This was a multicentre, randomised, double‐blind, active‐ and vehicle‐controlled, 4‐arm, parallel‐group trial

Participants

Inclusion criteria of the trial

• Global severity score (GSS) of at least 3

• Age: older than 18 years

• At least 10% of psoriatic scalp involvement

• Patients with history of psoriasis of the body

• Investigator's assessment of clinical signs: at least 1 sign rated as 'moderate' and the other as at least 'slight'

• Investigator's Global Assessment (IGA): 'mild' to 'severe'

Exclusion criteria of the trial

• Within previous 6 months: systemic treatment with biologicals (e.g., alefacept efalizumab, etanercept, infliximab)

• Within previous 4 weeks: PUVA‐ or grenz ray therapy, systemic treatment with possible effect on scalp psoriasis (e.g. corticosteroids, vitamin D analogues, retinoids, immunosuppressants)

• Within previous 2 weeks: topical treatment of the scalp (except for medicated shampoos and emollients), topical treatment of the face, trunk or limbs with very potent corticosteroids, UVB therapy

• Planned initiation of or changes to concomitant medication that could affect scalp psoriasis (e.g. beta blockers, antimalaria drugs, lithium)

• Planned exposure to the sun that may affect course of disease

• Current diagnosis of erythrodermic, exfoliative or pustular psoriasis

• Skin infection (fungal, bacterial, viral, parasitic)

• Atrophic skin on the scalp

• Co‐morbidity: abnormality of calcium homeostasis associated with clinically significant hypercalcaemia, severe renal insufficiency, severe hepatic disorder

Washout period

• 2 weeks: topical anti‐psoriatic treatments and UVB‐therapy (according to exclusion criteria)

• 4 weeks: systemic anti‐psoriatic treatment (according to exclusion criteria)

• 6 months: systemic biological treatments (according to exclusion criteria)

Baseline characteristics

• Age (years mean ± SD): A: 47.9 ± 15.4, B: 49.5 ± 15.9, C: 50.1 ± 16.6, D: 49.6 ± 15.8

• Females N (%): A: 282 (52.1), B: 323 (58.1), C: 151 (55.5), D: 75 (55.1)

• Total sign score (TSS, mean ± SD): A: 6.7 ± 1.9, B: 6.9 ± 1.8, C: 6.8 ± 1.8, D: 7.0 ± 1.9

Interventions

A: calcipotriene 50 µg/g plus betamethasone dipropionate 0.5 mg/g gel, once daily for 8 weeks (N = 541 participants)

B: betamethasone dipropionate 0.5 mg/g gel, once daily for 8 weeks (N = 556 participants)

C: calcipotriene 50 µg/g gel, once daily for 8 weeks (N = 272 participants)

D: placebo‐vehicle, once daily for 8 weeks (N = 136 participants)

Assignment in 4:4:2:1 ratio

Quote (page 457): "Patients graded to have "absence of disease" [...] could stop treatment with study medication at the investigator's discretion, but after implementation of a protocol amendment were required to remain in the study and attend all clinic visits."

Outcomes

Primary outcome of the trial

1. IGA: "absence of disease"/"very mild disease" (week 8)

Secondary outcomes of the trial

1. IGA (week 2 and 4)

2. TSS (week 1, 2, 4, 6 and 8)

3. Patient's assessment of overall response: "cleared"/"almost clear" (week 8) ⇒ matched with PGA: responder

4. Redness (week 1, 2, 4, 6 and 8)

5. Thickness (week 1, 2, 4, 6 and 8)

6. Scaliness (week 1, 2, 4, 6 and 8)

7. Compliance (week 1, 2, 4, 6 and 8)

8. Adverse events (AE) (week 8)

9. Number of patients with at least 1 AE

10. Withdrawal due to AE (week 8)

11. Blood samples (week 8)

Definition:

IGA (6‐point scale): disease severity rated as'absence of disease', 'very mild disease', 'mild disease', 'moderate disease', 'severe disease' and 'very severe disease'

Patient's assessment of overall response (7‐point scale): extent and severity of scalp lesions rated as 'worse', 'unchanged', 'slight improvement', 'moderate improvement', 'marked improvement', 'almost clear' and 'cleared'

AE: including severe AEs

Blood samples: serum calcium and serum albumin

Erythema, thickness, scaling score: 0 = no signs, 1 = slight signs, 2 = moderate signs, 3 = severe signs, 4 = very severe signs

TSS (0‐12): sum of erythema, thickness, scaling scores

Visits: baseline, week 1, 2, 4, 6 and 8

Notes

This trial was supported by LEO Pharma A/S, Ballerup, Denmark.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote (page 456): "[...] according to a preplanned computer‐
generated randomization code list [...]"

Comment: probably adequate sequence generation

Allocation concealment (selection bias)

Unclear risk

This was not stated

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Quote (page 457‐8): "All randomized patients were included in the full analysis set and were analysed for efficacy. [...] using last observation carried forward [...]"

Comment: ITT analysis and appropriate imputation method performed

Selective reporting (reporting bias)

Low risk

All reported results were pre‐specified outcomes in the methods section

Other bias

Low risk

No other source of bias identified

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quote (page 457): "Packaging and labelling of the investigational products or placebo contained no evidence of their identity. [...] No effects of the Investigational Products revealed the identity of the individual treatment allocations"

Comment: blinding probably sufficient

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Quote (page 457): "Packaging and labelling of the investigational products or placebo contained no evidence of their identity. [...] No effects of the Investigational Products revealed the identity of the individual treatment allocations"

Comment: blinding probably sufficient

Methods

This was a mono‐centre, randomised, open‐labelled, parallel‐group trial

Participants

Inclusion criteria of the trial

• Patients with scalp psoriasis with scaly erythematous plaques

• At least 10% of psoriatic scalp involvement

• Moderate lesion score (LS, 3 < LS < 6)

Exclusion criteria of the trial

This was not stated

Washout period

This was not stated

Baseline characteristics

• Age (years, mean ± SD): A: 49 ± 16, B: 45 ± 16

• Females N (%): A: 19 (47.5), B: 18 (46.2)

• LS (mean ± SD): A: 5.28 ± 0.91, B: 5.18 ± 1.00 ⇒ matched with TSS

Interventions

A: betamethasone dipropionate lotion plus RV3423A shampoo alternated with extra gentle shampoo, every day alternation for 4 weeks (N = 40 participants)

B: betamethasone dipropionate lotion plus extra gentle shampoo, once daily for 4 weeks (N = 39 participants)

Outcomes

1. LS (week 2, 4 and 8)

2. Erythema (week 2, 4 and 8)

3. Induration (week 2, 4 and 8)

4. Desquamation (week 2, 4 and 8)

5. Pruritus (week 2, 4 and 8)

6. Investigator global efficacy assessment (IGA) (week 4 and 8)

7. Cosmetic acceptability (week 8)

8. Patients' satisfaction (week 8)

Definition:

LS (0 to 9): sum of desquamation, erythema and induration scores

Outcomes 2 to 4: rated on scale from 0 to 3: 0 = absence, 3 = very severe

IGA: not defined in this abstract ('healing' matched with 'clear')

Visits: baseline, weeks 2, 4 and 8 (not relevant)

Notes

Total sign score (TSS) in data analysis calculated from LS by the review author

After 4 weeks, participants were treated until week 8 in a manner that was not relevant for this review

This was a conference abstract

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote (page 391): "randomized"

Comment: insufficient detail was reported about the method used to generate the allocation sequence

Allocation concealment (selection bias)

Unclear risk

This was not stated

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk