CLIN 508 - Clinical Trials in Specific Disease Clinical Research School of Health Sciences, HUMBER COLLEGE, Ontario, Canada.

1. A ClinicalandTechnicalAssessmentof Biologics
for Moderate-to-SeverePlaquePsoriasis:Key
Issuesin Planning,Implementationand
Reporting
Tahsinul Anam, Mona Ahadzadegan Ahani, Rachel Armstrong, Olayinka Abidemi
Awofodu, Manuel Reyes Caballero, Neeti Galwankar, Nishreen Leila, Nicole Ricker &
Lavanya Uruthiramoorthy

2. OVERVIEW OF MODERATE-TO-SEVERE
PLAQUE PSORIASIS
Tahsinul Anam

3. Managing Psoriasis
Clinical Presentation
Epidemiology and Pathophysiology

4. What is Psoriasis?
• A common, life-long, genetic, autoimmune skin
disease
• Circumscribed areas of thick, red, scaly skin
• “psoros” meaning “rough, scabby”
• Term first used (along with “lepra”) by
Hippocrates (460-377 B.C.) in Corpus
Hippocraticum
• Von Hebra first to distinguish psoriasis from
leprosy in 1841

5. • Psoriatic arthritis
• ~30% of patients with psoriasis
• Depression and alcohol abuse
• Obesity
• Severe psoriasis
• 7x risk for developing myocardial infarction
• increased mortality
• ~5 year shorter life span
Psoriasis is Not Just a Skin
Disease

6. • Fear of contagion from others
• “modern day lepers”
• Low self esteem
• “something’s wrong with me”
• Need to cover up
• “I don’t want anyone to see”
• Sexual impairment
• Hand/foot lesions
• Itching
• Arthritis
Psoriasis Significantly Impairs
Quality of Life

7. 7
DERMIS
STRATUM
BASALE
STRATUM
SPINOSUM
STRATUM
GRANULOSUM
STRATUM
CORNEUM
Proliferation
Immaturity
Neutrophil
accumulation
DisorganizedN
O
R
M
A
L
P
S
O
R
I
A
S
I
S

8. • Scalp (80%)
• Elbows (78%)
• Legs (74%)
• Knees (57%)
• Nails (10-55%)
• Gluteal cleft
• Palms/soles (12%)
Classic Anatomic Locations for
Psoriasis

9. • Chronic plaque psoriasis
• Guttate psoriasis
• Erythrodermic psoriasis
• Generalized pustular psoriasis (von Zumbusch)
• Localized pustular psoriasis
• Palmaris et plantaris
• Acrodermatitis continua
• Inverse psoriasis
Clinical Variants

10. 5
19
21
29
31
71
79
94
0 20 40 60 80 100
Other
Fatigue
Burning…
Bleeding
Tightne…
Skin…
Itching
Scaling
Percentage of respondents (n = 17,425)
Symptoms of Psoriasis
• Adapted from Krueger G et al. Arch Dermatol 2001; 137: 280–4.
Mostfrequently
experiencedsymptoms

11. Epidemiology
• Common skin disorder
• Prevalence variable: ~ 0.3–2.5%1
• Prevalence equal in males and females2
• Estimated incidence: ~ 60 per 100,000 per
year3
1. Plunkett A et al. Australas J Dermatol 1998; 39: 225–232. 2. Barker J. Clin Exp Dermatol 2001;26(4):321-5. 3. Bell LM et al. Arch
Dermatol 1991; 127: 1184–7.

12. Age of Onset
• Mean age: ~ 23–37 years1
• Current theory:
2 distinct peaks with possible genetic associations1
• Early onset (16–22 years)2
• More severe and extensive
• More likely to have affected first-degree family
member
• Late onset (57–60 years)2
• Milder form
• Affected first-degree family members nearly
absent

13. Genetic Influence
• Evidence suggests strong genetic association
• Studies of monozygotic twins show
concordance for psoriasis (e.g. 64% in a
Danish Study)1
• Multiple susceptibility loci have been
identified2
• Disease expression
• likely result of genetic and environmental
factors2
1.Brandup F et al. Acta Dermato-Vernerol 1982; 62L: 229–36. 2. Barker J. Clin Exp Dermatol 2001; 26(4):
321–5.

14. Common Trigger Factors
for Psoriasis
• Infections (e.g. streptococcal, viral)
• Skin trauma (Koebner phenomenon)
• Psychological stress
• Drugs (e.g. lithium, beta blockers)
• Sunburn
• Metabolic factors (e.g. calcium deficiency)
• Hormonal factors (e.g. pregnancy)
1. Dermatology Expert Group. Therapeutic guidelines: dermatology. Version 3. Melbourne: Therapeutic Guidelines Limited, 2009.
14

15. Psoriasis is a T-cell Mediated
Autoimmune Disease
• Current hypothesis:
• Unknown skin antigens stimulate
immune response
• Antigen-specific memory T-cells are
primary mediators
• Leads to impaired differentiation and
hyperproliferation of keratinocytes
1. Lee M et al. Australas J Dermatol 2006; 47: 151–9.
15

16. 16

18. CURRENT TREATMENTS
Tahsinul Anam

19. • Lubrication
• Removal of scales
• Slow down lesion
proliferation
• Pruritus management
• Prevent complications
• Lessen patient stress
• Season and climate

20. Step 1
Anthralin Calcipotriene
Coal Tar
Tazarotene Intralesional Steroid
Topical Steroid
Climatotherapy Moisturizers Keratolytics
Step 2
PUVA PUVA +
Step 1 agent
Acitretin
Step 3
Methotrexate Cyclosporine
Rotational:
12-24 months
of each
step 3 agent
Supplementary
Tx
Step 4
Enbrel/Remicade/Amevive/Raptiva

21. Topical Therapies for Psoriasis
• Corticosteroids:
• mid-high potency for most areas
• low potency for face and intertriginous areas
• Calcipotriene (Dovonex®):
• works best in combination with topical
corticosteroids
• Tazorotene (Tazorac®):
• works best in combination with topical
corticosteroids
• Tacrolimus (Protopic®):
• for face and intertriginous areas
• Ointments, creams, gels, foams, sprays,
shampoos, and medicated tape all available

22. Older Systemic Therapies for
Psoriasis
• Phototherapy: UVB, narrow-band UVB, PUVA,
Excimer laser
• Methotrexate
• Acitretin (Soriatane®)
• Cyclosporine

23. • Alefacept (Amevive®):
• LFA3-tip, targets CD2+ T cells
• Etanercept (Enbrel®):
• soluble TNF- receptor
• Adalimumab (Humira®):
• human anti-TNF- mAb
• Infliximab (Remicade®):
• chimeric anti-TNF- mAb
• Golimumab (Simponi®):
• human anti-TNF- mAb
• Ustekinumab (Stelara®):
• human anti-IL-12/IL-23 mAb
Biologic Treatments for
Psoriasis

24. TRENDS IN CURRENT CLINICAL TRIALS
Mona Ahadzadegan Ahani

25. • The primary goal of current research in plaque
psoriasis:
• Increased efficacy & tolerability
• Fewer AE
• Combination, rotational, or sequential treatment
strategies
• Resistance to existing therapies:
• More therapeutic options
• New formulations
• New target and mode of action

26. • Topical agents - for minimal disease
• First-line therapy: phototherapy
• The most effective UVB phototherapy: NBUVB
phototherapy
• Example: Efficacy of methotrexate and NBUVB
combination was investigated
• Improve psoriasis in significantly less time, with lower
cumulative UVB
UVB therapy: production of non-melanoma skin cancer

27. • Second-line therapy: Traditional, non-biologic
systemic agents (MTX, CSA)
• Long-term toxicity
• Treatment resistant
• Safety concerns related to their long-term use
• Methotrexate:
• The gold-standard comparator for new
interventions such as biologics
• Despite being highly effective:
• fail to respond to methotrexate monotherapy
• risk of liver toxicity

28. Topical agents
for minimal
disease
Phototherapy
(First-line
therapy)
Traditional
systemic
agents
(Second-line
therapy)
Biologics
(Third-line
therapy)
The most effective UVB
phototherapy: NBUVB
phototherapy
High risk of AEs & SAEs,
resistance to the agents
For failure, intolerance or
co-morbidities with
traditional systemic agents

29. • Third-line therapy: Biologics
• For failure, intolerance or co-morbidities with
traditional systemic agents
• Choice of biologic
• Not clear which one is the best first choice
• Often lose response over 1 year
• Add phototherapy or MTX
• Switch to another biologic

30. Advantages
More effective than
conventional
treatments
Few drug
interactions
Avoid absorption
issues
Novel MOA &
focused target
Disadvantages
Increased common & rare infections
(TB)
Must stop drug during infection/surgery
Cannot be used together (with
other biologics)
Tolerance/Antibody
formation
IV or SQ admin
Cost
Long term side
effects ??
Biologics

31. Etanercep
• first TNF inhibitor
• Serious infections
Adalimumab
• third TNF inhibitor after etanercept
• Serious infections (TB), cases of lymphoma
Ustekinumab
• Blocks two cytokines, IL-12 and IL-23
• Target different points in the cascade of immune-system signalling
molecules
• Rsk of SAE: major cardiovascular events
Secukinumab

32. Secukinumab (AIN457):
• A fully human anti IL-17A
• An investigational biologic treatment for
moderate-to-severe psoriasis
• Has shown early promise in a phase II trial,
currently being further investigated in a phase III
trial
• Anti IL-17s : (new class of drugs)
• A new therapeutic target in psoriasis
• Preliminary clinical results: blocking IL-17
reduces disease severity
• Animal models: blocking IL-17 reduces psoriasis-
like pathology
• PASI 100

33. Secukinumab (AIN457):
• A randomized, double-blind, phase II, placebo-controlled,
parallel by Novartis
• July 2009 - Dec 2010
• Objective: To evaluate the safety and efficacy of three
induction regimens of secukinumab
• Result: The investigational anti‐IL‐17 monoclonal
secukinumab showed significant efficacy and tolerability in
up to 81% of patients

34. “September 27, 2012 - Novartis announced today
new Phase II data showing AIN457 (secukinumab)
may significantly improve moderate-to-severe
plaque psoriasis on the hands, feet and nails...”
“Given what we've seen in phase II, where all these therapies were
well tolerated and continued to be effective, it is very unlikely that
there will be something in phase III to prevent regulatory
approval,” – Dr. Kim Papp

35. • Challenge: The selection of safer and more
effective agents to treat plaque psoriasis,
particularly when it comes to biologics
• At the moment, psoriasis therapy is dominated by:
• Amgen/Pfizer's etanercept
• Abbott Laboratories' adalimumab
• Ustekinumab from Janssen Biotech
• Novartis’ secukinumab may offer new
therapeutic options for plaque psoriasis in the
near future.

36. Secukinumab Trial Design and Issues
Nishreen Leila

37. Immune Modulators
• TGN1412: humanized mAb against CD28 Tcell
receptors developed by TeGenero
• Phase I trial conducted in UK on March 13 2006
• Resulted in the hospitalization of all 6 subjects within
a few hours of taking the drug
• Drug induced cytokine storm caused near fatal organ
failure

38. Starting Dose for Phase I trials
involving Immune Modulators
• Starting dose determination
• Extreme caution in determining the
dose for a first in man trial
• Use “minimal anticipated biological
effect level” MABEL instead of “no
observed adverse effect level” NOAEL
• Preclinical studies in an appropriate
animal model and invitro studies are
critical
• Explains the longer( 30 day) CTA
approval time

39. SecukinumabRandomized,DoubleBlind,
Placebo-controlled,PhaseII Regimen-findingStudy
404 patients
randomized
Randomization 1
1:2:2:1
Randomization 2
1:1
Responders:PASI
75

40. Randomized Withdrawal Design :
“Enriched Enrolment”
• Patients who respond positively in the
induction phase are re-randomized to
active or placebo arm
• To study long term effects of treatment and
length of treatment
• Experimental treatment is limited to
patients who respond
• Shortened time on placebo arm
• Disadvantages:
• Carryover effect
• Longer study duration

41. Ongoing Phase III
Secukinumab Trials
• Treatment of nail and palmoplantar psoriasis
• Comparison of IV vs SC administration of drug
• Prefilled syringes and auto-injectors for drug
administration
• Long term safety
• Comparison to etanercept
• Two pivotal extension studies recruiting 740 and 1220
patients respectively: long term efficacy and safety.
Patients recruited for this study will be responders
from previous phase III studies.

42. Placebo Controlled Trials
• Psoriasis trials are placebo controlled
• Good trial design
• Chronic nature of the disease
• Account for the Placebo Effect

43. Placebo Effect: Conditioning
• Immune system and CNS are
linked
• Increased stress levels linked to
psoriasis flare ups
• Release of neurotransmitters in
response to a placebo may
positively alter the immune
system
• Common to see 15-20%
improvement of PASI score on
placebo

44. EnrollmentCriteria in a PsoriasisBiologic
Trial: Moderateto Severe Psoriasis
• Body Surface Area
• Intensity of local signs
and symptoms
• Response to previous
treatments

45. Placebo Effect: Eligibility Creep
• What is best for my patient?
• Tendency for patients to meet
eligibility criteria when they are close
to the eligibility criteria by scoring
them on the higher end of scale
• Patient is enrolled in the trial and
randomized to placebo arm
• Patient is now scored as usual: this
score is now lower than the score
used to enroll
• “Placebo effect” artifact introduced by
the investigator

46. Eligibility Creep: Characteristics
• Significant improvement observed between
baseline and first visit with little
improvement after
• Seen in trials that have subjective outcome
measures that are also used as eligibility
criteria

47. Other Issues in Trial Design
• Absence of head to head comparator trials
• More beneficial for patients
• Required for physicians to make good decisions
based on strong scientific evidence
• Subjectivity in eligibility determination
may result in the exclusion of patients
from participating in a trial

48. EFFICACY & ENDPOINTS
Nicole Ricker

49. Psoriasis Assessment Tools
• What is being measured: Psoriatic lesions on the surface
of the skin (redness, thickness, and scaliness)
• How: Various assessment tools (e.g. the Psoriasis Area
Severity Index) generate a numerical score that represent
severity of psoriasis
• When: clinical trials and clinical practice
• Why: Measure change in psoriasis severity to assess
medical need (clinical practice) and efficacy of treatment
(clinical trial)
• Requirement: STANDARDIZATION!

50. PASI (Psoriasis Area and
Severity Index)
The affected area and lesion characteristics are entered in a formula that
results in a score from 0 to 72. The PASI is most often used in clinical trials
PGA (Physician’s Global
Assessment)
The PGA is a 5, 6, or 7-point ordinal rating ranging from ‘‘clear’’ to ‘‘very
severe psoriasis’’
PaGA (Patient’s Global
Assessment)
The PaGA is an ordinal rating ranging from ‘‘clear’’ to ‘‘very severe psoriasis’’
assessed by the patient
SAPASI (Self-Administered PASI) The SAPASI is a structured PASI-like instrument designed for patient self-
assessments of severity
PASS (Psoriasis Assessment
Severity Score)
The affected area and plaque characteristics are entered in a formula that results in
a score from 0 to 140. Infiltration is given more weight than erythema and scaling.
LS-PGA (Lattice System Physician’s
Global Assessment)
The LS-PGA integrates ranges of involved BSA and the overall plaque morphology
in which infiltration is given more weight
SPASI (Simplified PASI) The SPASI equals the sum of the average redness, thickness, and scaling of all the
psoriasis lesions multiplied by the percentage of body surface area involved
PEASI (Psoriasis Exact Area and
Severity Index)
The PLASI is derived from the PASI but uses actual BSA percentages instead of an
area score
PLASI (Psoriasis Long-based Area
and Severity Index)
The PLASI is derived from the PASI but uses six BSA groupings with finer
partitioning for smaller extents of BSA

51. Types of Assessments
• Psoriasis Area and Severity Index (PASI): The affected area and lesion
characteristics are entered in a formula that results in a score from 0 to
72. The PASI is most often used in clinical trials
• Physician Global Assessment (PGA): The PGA is a 5, 6, or 7-point
ordinal rating ranging from ‘‘clear’’ to ‘‘very severe psoriasis’’
• Quality of Life Measures
• Biopsies and Photographs
Advantages Disadvantages
PASI •Widely used in clinical trials
• Large scale (0-72)
•Not widely used in clinical practice
•Does Not discriminate when body-
surface-area is low
PGA •Widely used in clinical trials
•Similar to the assessments
physicians actually perform in
clinical practice
•Easy to understand
•Requires definition of each score
•Does not discriminate small
changes (uses a 7 point scale)

52. Assessment Selection
• Consider population, trial design, and
psoriasis type
• Consider historical findings and
previous successful study designs
• Consider the implications of the type of
measure used
• Use a combination

54. Plaque Characteristics
http://www.dermnetnz.org/scaly/pasi.html

55. Endpoints in Clinical Trials
• Purpose of endpoint: to demonstrate that more patients
achieve clinically meaningful success with the drug treatment
than with placebo
• ‘Clinically Meaningful Success’ can be hard to define
• A large improvement and a small improvement can be ‘clinically
meaningful’
• Combine with other measures (QofL, PGA, EEG etc.)
• Standard: at least 75% improvement in disease OR 75%
improvement in the PASI score

56. Secukinumab Trial: Evaluating
Efficacy
Primary Outcome Measure: Efficacy of secukinumab in subjects with
moderate to severe chronic plaque-type psoriasis
• Cumulative rate of subjects with Loss of Psoriasis Area and Severity
Index (PASI) 75 response (75% improvement on PASI scale)
Secondary Outcome Measures (Safety)
• Change in Psoriasis Area and Severity Index (PASI)
• Investigator Global Assessment (IGA) 2011 score
• Time to Psoriasis Area and Severity Index (PASI) 75 response
• Hemoglobin count, hematocrit count, red blood cell count, white blood
cell count
• Electrocardiogram (ECG) test results - measured in degrees
• Adverse events – measured in % of patients with any adverse events
• Change in quality of life – measured by change in questionnaire scores

57. SAFETY PARAMETERS & ADVERSE
REACTIONS
Rachel Armstrong

58. Safety Parameters in Biologics Trials
• AEs and SAEs
• Haematology
• Blood and urine analysis
• Vital signs
• ECG Assessments
Overall, relatively simple assessments to perform...

59. Key Challenges: Safety Profile
• Lack of long-term data
• Accurate long-term safety profile requires AE
collection over longer time frame with broader
patient population
• Critical for ensuring overall patient safety
• Plaque psoriasis is a lifelong disease
• Long term administration of medication seems
to be key to helping patients manage symptoms

60. Key Challenges: Adverse Events
• Collection of AEs
• Conflicting evidence
• Phase I and II trials with relatively few patients
• Inadequate ascertainment / classification of AEs
• Inconsistencies in reported Aes
• AEs reported as secondary outcomes and not pre-
specified
• Trials are powered for detection of significant
difference between groups for beneficial effect
• Estimates for adverse effects may lack precision

61. Adverse Events: Treatment-Related
Infection
• Primary drug action:
• Inhibition of the IL-17 pathway
• This pathway plays a role in protective immunity
• Infection rates:
• Must be monitored in both groups when
conducting a trial
• Future Steps:
• Until the generation of more safety data, patients
with a history of viral infection (HIV, Hepatitis)
should be excluded from trials

62. Adverse Events: MACEs
• Patient Risk:
• Psoriasis patients are at increased risk of
cardiovascular disease
• MACEs:
• Analyses of other biologics (e.g. briakinumab)
have raised concerns about increased risk of
Major Adverse Cardiovascular Events
• Future Steps:
• All future studies should incorporate safety
parameters to account for this risk, such as ECG
recordings

63. Adverse Events: Malignancy
• Patient Risk:
• Association between biologics and malignancies
such as skin cancer
• Risk of malignancy might be further increased if
patient has used phototherapy
• Next Steps:
• Need for patient counselling and regular check-
ups to reduce chance of malignancy
• Safety parameters for future secukinumab studies
should be designed to assess the incidence of
cancer

64. Safety Parameters &
Adverse Events Re-Cap...
• Safety Parameters
• Infection rates
• MACEs
• Malignancy
• Future Considerations…
• Larger, post-marketing studies will be required
• Additional safety parameters must be included to ensure
patient safety
• Protocols should pre-specify AEs based on pharmacological
mechanisms and data from earlier studies
• Systematic review should be conducted to build a complete
safety data set

65. INCLUSION & EXCLUSION CRITERIA
Neeti Galwankar

66. • Phase I: Healthy volunteers and patients to
study the PK/PD
• degree of psoriases on the PASI scale not
significant
• Phase II: moderate to severe psoriases on
PASI scale(Very thick lesions located in
‘difficult-to-treat’ regions, such as the palms
and soles)
• Phase III: Similar to phase II.
• Few targeted specific psoriatic populations
(eg. Nail, palmoplantar etc).

67. Inclusion Criteria
1. PASI score ≥ 12 at baseline (moderate to severe psoriases)
2. Body surface area ≥ 10%
3. Patients whose disease was inadequately controlled by
topical treatments, phototherapy, or previous systemic
therapy.
4. Male patients and female patients of childbearing age are
eligible if they are willing to use an effective method of
contraception during the study and for 4 months after the
last dose of study drug.
5. Age 18-65 yrs

68. Exclusion Criteria
1. Psoriasis other than chronic plaque-type
2. Ongoing use of prohibited psoriasis treatments such as conventional
systemic therapy (e.g. methotrexate, cyclosporine)
3. Biologic systemic therapy (eg, adalimumab, efalizumab, etanercept),
topical or systemic corticosteroids, ultraviolet light therapy, or other
investigational drugs, within specified time periods prior to study entry
• Rationale: Contraindication
4. Live vaccination within 6 weeks before first study drug administration;
and known immunosuppression, active infection, or history of active
tuberculosis
• Rationale: patient susceptible to infection
5. Patients with a history of congestive heart failure
• Rationale: Some biologics have been associated with cardiovascular
events. Eg: Briakinumab
• confound the results of the study(determine if the side effects are due to
the original disease or due to the drug)

69. Patient RecruitmentIssues Arising from
Inclusion/ExclusionCriteria
1. Most patients lie in mild – moderate. So, finding
patients in moderate- severe category difficult
1. Clinical variants excluded(eg. Gutate psoraises)
1. High rate of a number of co-morbidities.
• Challenging to evaluate impact on co-morbidities
• Prevents the evaluation of drug-drug interactions
• Phase IV trials to understand co-morbidities

70. STATISTICAL CONSIDERATIONS
Neeti Galwankar

71. • Placebo effect-size of the target population and during
data analysis
• Dropout rate- parallel design is to cross over the non-
responding patient to the other arm to see if that
makes a difference in response
• Compromised blinding- Due to the visual nature of the
disease. Solution is to have separate individuals
treating the patient and assessing disease progression
• Variations in disease severity over time- sequential
evaluation of disease response using standardized
criteria

72. ETHICAL CONSIDERATIONS
Lavanya Uruthiramoorthy

73. • Patient Autonomy
• Informed Consent
• Language barriers
• Coercive influences
• Beneficence
• Conflict of interest
• Bias in the data presented
• Competing studies
• Non-maleficence
• Use of placebos
• Distributive Justice
• Patient treatment after study completion

74. SELECTION OF INVESTIGATORS &
SITES
Lavanya Uruthiramoorthy

75. Selection Criteria
 Timeliness
 Investigator interest, motivation & reputation
 Available resources
 Patient referral
 Previous experience & performance in studies
 Previous audits
 Recruitment history
 Acceptable facilities and resources
 Access to the appropriate patient population
 Trained & qualified staff
 Low staff turnover
 Budgetary factors
 Sponsor relationship

76. Feasibility Questionnaires
• Patient population
• Staffing
• Research Ethics Board information
• Proper equipment
• Competing studies

77. Site Assessment Visit
• Investigators’ interest
• Time availability
• Methods of recruitment
• Staff involvement
• Equipment
• Suitability of location
• Storage facilities

78. Site & Investigator Exclusion
• Low recruitment rates
• Too many queries
• Poor quality of data
• Insufficient/inexperienced staff
• Inadequate facilities/equipment
• Presence of competing studies
• Lack of PI involvement
• Infrequent IRB/REB meetings

79. Suggestions
• Early in the planning of the trial
• Review relevant medical/scientific literature
• Conduct thorough Feasibility Questionnaires and
Site Assessment Visits
• Consider opinions of all stakeholders

80. PATIENT RECRUITMENT STRATEGIES
Manuel Reyes Caballero

81. Patient Recruitment Strategies
• Key of a successful trial
• Delays in patient recruitments
• Higher cost of companies
• Slower time to market the product
• Loss of revenue
• Weakens statistical power
• No statistical significance

82. • Difficulty of recruiting subjects is low when
inclusion criteria are narrow.
• Aspects to consider for psoriasis recruitment:
• Biological drugs
• Psoriasis population percentage
• Seasonal changes
• Cost of psoriasis treatments
• Quality of life
• Retention of patients
• Incentives

83. Biological Drugs
• No cure for chronic plaque psoriasis
• Biological drugs target aspects of the immune system
• Effects in the immune system exclude many patients
• The record on existing safety data in biological agents
is limited
• Risk of side effect is very low

84. Psoriasis Population Percentage
• Psoriasis is the most prevalent autoimmune
disease in the United States
• Psoriasis affects ~2.2 % of the population
• ~2 to 3 % of the total population have psoriasis
• Psoriasis studies target usually enrollment
between 15-30 patients
• Psoriasis studies recruit 2 to 3 patients each
month during the fall/winter time while about 1
patient each month during summer time

85. Seasonal Changes
• UV rays causes damage in DNA and alter the
immune system
• In India in the summer months 43%
improvement of psoriasis vs 7% improvement
in the winter months
• Photosensitive psoriasis (PP), in whom the
condition is predominantly photodistributed
is severe in the summer months

86. Cost of Psoriasis
• Psoriasis drugs are very expensive
• Most health insurance do not cover psoriasis
drugs
• Cost of total direct and indirect healthcare of
psoriasis = $11.25 billion annually
• On average 60% of psoriasis patients missed
26 days of work/year because of their illness

87. Quality of Life
• 60% of people with psoriasis reported their
disease to be a large problem in their
everyday life
• Psoriasis has a great impact in females and
young people

88. Retention of Patients
• Most studies are double blinded, crossover
design
• Study = 2 arms, placebo and treatment
• Placebo = no cure = loss of interest

89. COMPLIANCE
Manuel Reyes Caballero

90. Compliance
• The follow up of recommendations by a doctor related
to patients behavior + patient's adherence to prescribed
drugs
• Poor compliance = failure of the study or reducing the
statistical power of the study
• If 30% of patients in a clinical trial had inadequate
compliance
• Need 2x as many patients
• There is a relatively high compliance in psoriasis studies
• Factors that can result in poor compliance:
• Vacation of patients to warm places with high radiation of
UV light
• Patient diet

91. INFORMED CONSENT
Olayinka Abidemi Awofodu

92. • Follows the guidelines laid out in the Declaration of
Helsinki and ICH-GCP
• Biologic treatments have more systemic adverse events
• It is included and explained/pointed out clearly to the patients/
clinical investigation subjects
• Challenge:
• The ability of the physician to explicitly describe the biologic to a
patient
• Procedures should be explained in a coherent, easy to
understand manner, within grade 6-8 language level
• Consent by the patient should be given freely and only
after the physician is confident that the patient has
understood all the involved risks and benefits.
• Language barrier
• A representative may be considered

93. BUDGET CONSIDERATIONS
Olayinka Abidemi Awofodu

94. Budget Considerations
• 3 major factors limit the process of biologic development:
1. Cost
2. Safety,
3. Time.
• Complicated task:
• all aspect of this study requires using skilled staff, professional
services and specialized equipment
• The Fair Market Value
• Cost associated with patient recruitment
• Planned on a fee-for-service basis with detailed per-patient
costs

95. REPORTING & PUBLICATIONS
STRATEGIES
Olayinka Abidemi Awofodu

96. • Issue:
• Non-publication of negative trials and non-reporting of
negative outcomes, coupled with redundant publication of
positive findings.
• ICMJE requires registration of trial methodology but
does not require registration of trial results
• A globally unified system
• to provide a better meta-analysis of the reports/data
generated from the trials
• better understanding of the disease, and therapeutic
trends
• Critique peer review must be employed
• discrepancies between the registered trial and
published results

97. CONCLUSION

98. QUESTIONS?