# Presentation: 683494

## Biostatistical Analysis of Pivotal
Studies

Shiowjen Lee, Ph.D., Mathematical Statistician
Office of Biostatistics
OPaSS, CDER, FDA

**Studies**
**Shiowjen Lee, Ph.D., Mathematical Statistician**
**Office of Biostatistics**
**OPaSS, CDER, FDA**

## Efficacy Evaluation in Pivotal Studies

**Primary:      Treatment Success, is defined **
**                     ****as % of patients with Overall **
**                     ****Lesional Assessment (OLA) **
**                     ****score of 0 or 1 at Wk 12**
**Secondary: **
**                     ****- Clinical signs/symptoms**
**                     ****- Overall global response**
**Others:        Scalp and nail psoriasis**

## Presentation of Efficacy Findings in Pivotal Studies

**Overall efficacy findings of oral tazarotene vs. placebo**
**Subgroup efficacy results by gender and by baseline OLA severity**
**Short-term efficacy of oral tazarotene in treating scalp and nail psoriasis**
**Relapse rate (short-term)**

## Baseline Demographic

| Study #
(enrollment) | Variable | Tazarotene | Placebo |
| --- | --- | --- | --- |
| 
048
(166, 171) | Gender
      Female
      Male | 
34 (20%)
132 (80%) | 
48 (28%)
123 (72%) |
|  | OLA score
      Moderate
      Severe
      Very severe | 
100 (60%)
64 (39%)
2 (1%) | 
105 (61%)
63 (37%)
3 (2%) |
| 
049
(182, 187) | Gender
      Female
      Male | 
63 (35%)
119 (65%) | 
48 (26%)
139 (74%) |
|  | OLA score
      Moderate
      Severe
      Very severe | 
121 (66%)
57 (31%)
4 (2%) | 
125 (67%)
56 (30%)
6 (3%) |

## OLA Score and Treatment Success at Wk 12

| OLA Score at 
Wk 12 | Study 048 |  | Study 049 |  |
| --- | --- | --- | --- | --- |
|  | Tazarotene
(n = 166) | Placebo
(n = 171) | Tazarotene
(n = 182) | Placebo
(n = 187) |
| 0 – None
1 – Minimal
2 – Mild
3 – Moderate
4 – Severe
5 – Very severe | 4 (2%)
22 (13%)
61 (37%)
64 (39%)
14 (8%)
1 (<1%) | 2 (1%)
4 (2%)
20 (12%)
94 (55%)
49 (29%)
2 (1%) | 7 (4%)
27 (15%)
65 (36%)
61 (34%)
22 (12%)
0 | 2 (1%)
7 (4%)
21 (11%)
102 (55%)
51 (27%)
4 (2%) |
| 
% of patients with treatment success  | 
26 (15.7%) | 
6 (3.5%) | 
34 (18.7%) | 
9 (4.8%) |
| Comparison1 | < 0.001 |  | < 0.001 |  |
| 1 P-value is based on Cochran-Mantel-Haenszel test controlling for analysis center. |  |  |  |  |

## Subgroup Results of Treatment Success – Study 048

| Subgroup | Tazarotene
(n = 166) | Placebo
(n = 171) |
| --- | --- | --- |
| Overall
 | 26 (15.7%) | 6 (3.5%) |
| Gender
     Female
     Male | 
9/34 (26%)
17/132 (13%) | 
3/48 (6%)
3/123 (2%) |
| Baseline OLA 
     Moderate
     Severe
     Very severe | 
19/100 (19%)
7/64 (11%)
0/2 (0%) | 
3/105 (3%)
2/63 (3%)
1/3 (33%) |

## Subgroup Results of Treatment Success – Study 049

| Subgroup | Tazarotene
(n = 182) | Placebo
(n = 187) |
| --- | --- | --- |
| Overall
 | 34 (18.7%) | 9 (4.8%) |
| Gender
     Female
     Male | 
15/63 (24%)
19/119 (16%) | 
7/48 (15%)
2/139 (1%) |
| Baseline OLA
     Moderate
     Severe
     Very severe | 
24/121 (20%)
10/57 (18%)
0/4 (0%) | 
7/125 (6%)
2/56 (4%)
0/6 (0%) |

## Scalp and Nail Psoriasis

**Evaluation of short-term efficacy of tazarotene treatment (12-wk).**
**Severity was evaluated based on a 5-point scale (0 = none, 1 = mild, 2 = moderate, 3 = severe, and 4 = very severe).**
**Analysis is performed regarding the percentage of patients having severity score of 0 at Wk 12.**

## Scalp and Nail Psoriasis – Severity Score of 0 at Wk 12

| Study 048 | Tazarotene | Placebo |
| --- | --- | --- |
| Scalp
Fingernail
Toenail
 | 35/130 (27%)
0/88 (0%)
0/86 (0%) | 9/128 (7%)
0/82 (0%)
1/88 (1%) |
| Study 049 | Tazarotene | Placebo |
| Scalp
Fingernail
Toenail | 41/152 (27%)
0/96 (0%)
0/94 (0%) | 19/160 (12%)
2/95 (2%)
0/101 (0%) |

## Relapse Rate

**Analysis is based on the patients who were treatment**** success at Wk 12 and had relapse during the 12-wk post-treatment.**
**Two definitions of relapse are considered:**
**Def. (a): Patients who fell back to ****	****	****	****   baseline OLA score or worse.**
**Def. (b): Patients whose achieved ****	****	****	****   maximal improvement from ****	****	****	****   baseline is reduced by more than ****	****	****   50%.**

## Relapse On or Prior to Wk 24

| Study # | 048 |  | 049 |  |
| --- | --- | --- | --- | --- |
| Treatment group | Tazarotene | Placebo | Tazarotene | Placebo |
| No. patients had trt. succ. at Wk 12 | 26 | 6 | 34 | 9 |
| 
Missing

Relapse (a)
Relapse (b) | 
2 (8%)

6 (23%)
9 (35%) | 
0

1 (17%)
3 (50%) | 
1 (3%)

3 (9%)
9 (26%) | 
1 (11%)

3 (33%)
3 (33%) |

## Summary of Statistical Analysis in Pivotal Studies

**Oral tazarotene is statistically superior to placebo regarding treatment success. Success rates are below 20% for both studies.**
**Female patients had higher success rates than males though male patients accounted for over 2/3 of study enrollment in each trial.**

## Summary of Statistical Analysis in Pivotal Studies (con’t)

**Treatment success decreases as baseline OLA score increases. A total of 15 patients (2%) had “very severe” OLA score at baseline. None in oral tazarotene group achieved treatment success at Wk 12. There is insufficient data to evaluate the efficacy claim of “*****very severe*****” plaque psoriasis.**

## Summary of Statistical Analysis in Pivotal Studies (con’t)

**Oral tazarotene demonstrates short-term efficacy in treating scalp psoriasis, but not nail psoriasis. Two and 1 patients in placebo group achieved severity score of 0 at Wk 12 in fingernail and toenail psoriasis, respectively. However, none was in oral tazarotene group.**** **

## Summary of Statistical Analysis in Pivotal Studies (con’t)

**Based on definition (a) and definition (b) of relapse, approximately 15% and 30% of patients, respectively, who were treatment success at Wk 12, had relapse at the 12-wk post-treatment period.**