A Clinical and Technical Assessment of Biologics for Moderate-to-Severe Plaque Psoriasis: Key

Issues in Planning, Implementation and Reporting

Tahsinul Anam, Mona Ahadzadegan Ahani, Rachel Armstrong, Olayinka Abidemi Awofodu, Manuel Reyes Caballero, Neeti Galwankar, Nishreen Leila, Nicole Ricker & Lavanya Uruthiramoorthy

OVERVIEW OF MODERATE-TO-SEVERE PLAQUE PSORIASIS

Tahsinul Anam

Managing Psoriasis

Clinical Presentation

Epidemiology and Pathophysiology

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

• 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

• 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

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DERMIS

STRATUM

BASALE

STRATUM

SPINOSUM

STRATUM

GRANULOSUM

STRATUM

CORNEUM

Proliferation

Immaturity

Neutrophil accumulation

Disorganized N O R M A L

P S O R I A S I S

• Scalp (80%)

• Elbows (78%)

• Legs (74%)

• Knees (57%)

• Nails (10-55%)

• Gluteal cleft

• Palms/soles (12%)

Classic Anatomic Locations for Psoriasis

• Chronic plaque psoriasis

• Guttate psoriasis

• Erythrodermic psoriasis

• Generalized pustular psoriasis (von Zumbusch)

• Localized pustular psoriasis

• Palmaris et plantaris

• Acrodermatitis continua

• Inverse psoriasis

Clinical Variants

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.

Mo

st f

req

uen

tly

ex

per

ien

ced

sym

pto

ms

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.

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

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.

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.

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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

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CURRENT TREATMENTS

Tahsinul Anam

• Lubrication

• Removal of scales

• Slow down lesion proliferation

• Pruritus management

• Prevent complications

• Lessen patient stress

• Season and climate

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 eachstep 3 agent

Supplementary

Tx

Step 4

Enbrel/Remicade/Amevive/Raptiva

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

Older Systemic Therapies for Psoriasis

• Phototherapy: UVB, narrow-band UVB, PUVA, Excimer laser

• Methotrexate

• Acitretin (Soriatane®)

• Cyclosporine

• 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

TRENDS IN CURRENT CLINICAL TRIALS

Mona Ahadzadegan Ahani

• 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

• 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

• 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

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

• 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

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

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

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

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

“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

• 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.

Secukinumab Trial Design and Issues

Nishreen Leila

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

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

Secukinumab Randomized, Double Blind, Placebo-controlled, Phase II Regimen-finding Study

404 patients

randomized

Randomization 1

1:2:2:1

Randomization 2

1:1

Responders:PASI

75

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

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.

Placebo Controlled Trials

• Psoriasis trials are placebo controlled

• Good trial design

• Chronic nature of the disease

• Account for the Placebo Effect

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

Enrollment Criteria in a Psoriasis Biologic Trial: Moderate to Severe Psoriasis

• Body Surface Area

• Intensity of local signs and symptoms

• Response to previous treatments

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

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

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

EFFICACY & ENDPOINTS

Nicole Ricker

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!

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

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)

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

Plaque Characteristics

http://www.dermnetnz.org/scaly/pasi.html

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

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

SAFETY PARAMETERS & ADVERSE REACTIONS

Rachel Armstrong

Safety Parameters in Biologics Trials

• AEs and SAEs

• Haematology

• Blood and urine analysis

• Vital signs

• ECG Assessments

Overall, relatively simple assessments to perform...

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

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

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

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

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

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

INCLUSION & EXCLUSION CRITERIA

Neeti Galwankar

• 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).

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

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)

Patient Recruitment Issues Arising from Inclusion/Exclusion Criteria

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

STATISTICAL CONSIDERATIONS

Neeti Galwankar

• 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

ETHICAL CONSIDERATIONS

Lavanya Uruthiramoorthy

• 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

SELECTION OF INVESTIGATORS & SITES

Lavanya Uruthiramoorthy

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

Feasibility Questionnaires

• Patient population

• Staffing

• Research Ethics Board information

• Proper equipment

• Competing studies

Site Assessment Visit

• Investigators’ interest

• Time availability

• Methods of recruitment

• Staff involvement

• Equipment

• Suitability of location

• Storage facilities

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

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

PATIENT RECRUITMENT STRATEGIES

Manuel Reyes Caballero

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

• 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

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

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

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

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

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

Retention of Patients

• Most studies are double blinded, crossover design

• Study = 2 arms, placebo and treatment

• Placebo = no cure = loss of interest

COMPLIANCE

Manuel Reyes Caballero

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

INFORMED CONSENT

Olayinka Abidemi Awofodu

• 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

BUDGET CONSIDERATIONS

Olayinka Abidemi Awofodu

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

REPORTING & PUBLICATIONS STRATEGIES

Olayinka Abidemi Awofodu

• 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

CONCLUSION

QUESTIONS?