Download Patient Registries and Participating in Clinical Trials

Patient Registries and
Participating in Clinical Trials
Susan L. Perlman M.D.
Clinical Professor of Neurology
Director, UCLA Ataxia Center
Medical Director, NAF
March 17, 2011
NAF AMM LA CA Bringing the
Ataxia World Together
March 17, 2011
NAF AMM LA CA Bringing the
Ataxia World Together
The Bottom Line
• Every ataxia patient must participate in
clinical trials.
• Every researcher designing a clinical trial
must make it accessible to all ataxia
patients.
• There will be exceptions to both of these
fiats, but they must be justified.
March 17, 2011
NAF AMM LA CA Bringing the
Ataxia World Together
TYPES OF CLINICAL TRIALS
TYPE
# SUBJECTS LENGTH
AIM OF STUDY
N of 1
1
Ongoing
Do I get better or stop getting
worse on this drug?
Pilot
Up to 20
All get drug
Weeks to
months
Is a larger study worth doing,
will there be problems?
Phase 1
20-80 normal or patient
in groups of 3
All get drug
2 years
Escalating doses to learn side
effects, safety, best dose
Phase 2
20-300
Placebo and
drug groups
Compassionate
trials do not use
placebo.
2 years
To assess potential for good
effects, as well as side effects.
Also designed as “futility”
study—to show a drug doesn’t
not work(fewer subjects, less$)
Phase 3
300-3000
Placebo and
drug groups
3-5 years
To prove efficacy
May include crossover design,
open extension trial
Phase 4
100’s-1000’s
Open drug use
Ongoing
To find out more about the
effects of an approved drug.
Every Ataxia Patient Must Participate in
Clinical Trials
1. Registries will enable you to be found.
These are rare diseases with very small
numbers of patients who can participate.
Every person counts.
2. Be knowledgeable about what makes a good
clinical trial—don’t make bad investments.
3. Speak up about the roadblocks to participation.
Become involved in planning the trials.
4. Be prepared to make sacrifices.
March 17, 2011
NAF AMM LA CA Bringing the
Ataxia World Together
Every Researcher Designing A Clinical
Trial Must Make It Accessible To All
Ataxia Patients.
• Design trials that can use the fewest patients over the
shortest period of time (this usually means testing better
drugs and using biomarkers).
• What is the rationale for excluding certain patients? Can
those excluded be used in other ways? Parallel or
compassionate studies?
But remember that a patient can participate in only one
trial at a time and that participation in some trials may
permanently disqualify participation in others.
• Reimbursing travel costs is essential for recruitment and
compliance. Telemedicine?
• Don’t expect the patients to make unreasonable
sacrifices.
March 17, 2011
NAF AMM LA CA Bringing the
Ataxia World Together
Registries
• Ataxia patients are some of the most
highly motivated research subjects
around, but they aren’t superhuman.
• The Cooperative Ataxia Research Network
and the National Ataxia Foundation are not
mind-readers.
• Every ataxia patient must be in a Registry.
March 17, 2011
NAF AMM LA CA Bringing the
Ataxia World Together
The National Ataxia Registry
for all ataxias, must sign a consent form and provide PHI
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National Ataxia Registry
C/o Registry Coordinator
Department of Neurology
McKnight Brain Institute at University of Florida
100 S. Newell Dr. L1-108
PO Box 100236
Gainesville, FL 32610-0236
Phone : 352-273-9194
Fax: 352-392-8058
Email: [email protected]
• Web Site: http://www.NationalAtaxiaRegistry.org
Has links to all the other registries.
March 17, 2011
NAF AMM LA CA Bringing the
Ataxia World Together
Rare Diseases Clinical Research Network Registry
for all ataxias
participants in the Clinical Research Consortium for SCA 1, 2, 3, and 6 are automatically registered
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http://rarediseasesnetwork.epi.usf.edu/CRC-SCA/register/registry.htm
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After you have read and agreed to the authorization, the Contact Registry form will appear on your screen.
This form asks you for information such as your (or your child's) name, address, birth date, place of birth,
email address, or items relevant to your (or your child's) disorders:
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Ataxia telangiectasia
Ataxia with oculomotor apraxia (AOA) type 1
Ataxia with oculomotor apraxia (AOA) type 2
Ataxia with vitamin E deficiency (AVED)
Ataxia, unknown cause
Autosomal recessive ataxia of Charlevoix-Saguenay (ARSACS)
Dentatorubral-pallidoluysian atrophy (DRPLA)
Fragile X tremor-ataxia syndrome (FXTAS)
Friedreich's ataxia
GAD ataxia
Gluten ataxia
Mitochondrial ataxia
Mitochondrial recessive ataxia syndrome (MIRAS; POLG mutation)
Multiple system atrophy-cerebellar type (MSA-C)
Olivopontocerebellar atrophy (OPCA)
Paraneoplastic ataxia
Spinocerebellar ataxia 1(SCA1)
Spinocerebellar ataxia 2(SCA2)
Spinocerebellar ataxia 3(SCA3/Machado Joseph disease/MJD)
Spinocerebellar ataxia 4(SCA4)
Spinocerebellar ataxia 5(SCA5)
Spinocerebellar ataxia 6(SCA6)
Spinocerebellar ataxia 7(SCA7)
Spinocerebellar ataxia 8(SCA8)
Spinocerebellar ataxia 10(SCA10)
Spinocerebellar ataxia 11(SCA11)
Spinocerebellar ataxia 12(SCA12)
Spinocerebellar ataxia 13(SCA13)
Spinocerebellar ataxia 14(SCA14)
Spinocerebellar ataxia 15(SCA15)
Spinocerebellar ataxia 16(SCA16)
Spinocerebellar ataxia 17(SCA17)
Spinocerebellar ataxia 18(SCA18)
Spinocerebellar ataxia 19(SCA19)
Spinocerebellar ataxia 20(SCA20)
Spinocerebellar ataxia 21(SCA21)
Spinocerebellar ataxia 22(SCA22)
Spinocerebellar ataxia 23(SCA23)
Spinocerebellar ataxia 24(SCA24); Spinocerebellar Ataxia, Autosomal Recessive 4; SCAR4
Spinocerebellar ataxia 25(SCA25)
Spinocerebellar ataxia 26(SCA26)
Spinocerebellar ataxia 27(SCA27)
Spinocerebellar ataxia 28(SCA28)
Spinocerebellar ataxia 29(SCA29)
Spinocerebellar ataxia 31(SCA31)
Sporadic ataxia (onset before 20 years)
Sporadic ataxia (onset between 20-50 years)
Sporadic ataxia (onset after 50 years)
March 17, 2011
NAF AMM LA CA Bringing the
Ataxia World Together
CINCH
for episodic ataxias
• http://rarediseasesnetwork.epi.usf.edu/cinch/index.htm
• CINCH
• Clinical Investigation of Neurologic Channelopathies
• is a collaborative effort of doctors, patient
organizations, and federal health agencies that
want to learn more about these diseases so that
ultimately they can offer better treatments to
patients.
March 17, 2011
NAF AMM LA CA Bringing the
Ataxia World Together
Friedreich’s Ataxia Registry
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http://www.curefa.org/registry.html
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The FARA patient registry is the only worldwide registry of Friedreich’s ataxia patients. This
registry currently holds the demographic and clinical information on >1200 Friedreich’s ataxia
patients from across the United States and internationally. This registry was created to serve the
patient, physician, and research communities.
For the Patient Community
Participation in the FARA patient registry ensures that patients are informed about opportunities to
participate in clinical research studies and kept up-to-date on the progress of clinical trials.
For the Physician
The homepage of the FARA patient registry website, www.curefa.org/registry, is a place that you
can go to find an up-to-date listing of ongoing clinical trials for FA. You can refer your FA patients
to the patient registry so that he/she can consider registering. FARA can provide you with registry
brochures that you can give your patients to assist with the referral process.
For the Researcher
The FARA patient registry is a patient recruitment and communications tool for both academic and
industry sponsored clinical research studies and trials. The registry coordinator can perform
queries based on the inclusion/ exclusion criteria of a study and send patients information about a
study for which they qualify. Patients can be contacted by the registry coordinator via e-mail, mail,
or by telephone. Informational postings can also be added to the registry homepage as well as the
FARA website and in the FARA newsletter. FARA is committed to assisting researchers with study
recruitment and participation.
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March 17, 2011
NAF AMM LA CA Bringing the
Ataxia World Together
Becoming A Knowledgeable Consumer
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General trial info:
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Determining dosage maximum – is it safe?
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How will my confidentiality be maintained? Identity disclosure issues
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Explain need for exclusionary and placebo process
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How to choose a trial and where to go
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Telemedicine for trials?
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Face to face presentation of each trial’s process/benefit and communicate to potential
participants: Why do we have to discontinue our current meds? What are the measures of
confidentiality required or available? Type of contact?
In terms of ongoing trials:
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Why is this trial being done?
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What’s the long term benefit?
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Explain what you’ll do in the trial—why will these measures show change?
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Present info in clear format for FAQs, ex.: travel expenses, risks, disclosure
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What are the side effects, benefits
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How will participation affect or be affected by my current medications?
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Concealment/placebo affects
March 17, 2011
NAF AMM LA CA Bringing the
Ataxia World Together
Roadblocks
March 17, 2011
NAF AMM LA CA Bringing the
Ataxia World Together
Sacrifices
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Time
Money
Confidentiality
Ultimately, choosing and giving up one
drug trial for another.
March 17, 2011
NAF AMM LA CA Bringing the
Ataxia World Together
Roadblocks for Clinical Researchers
• Picking the right drugs.
• Designing the trial properly—number of patients,
measures/biomarkers, length of study, placebo,
how many sites.
• Getting the FDA to agree.
• Getting funding.
• Finding sites and getting them approved.
• Finding subjects.
• Doing the work in a timely fashion.
March 17, 2011
NAF AMM LA CA Bringing the
Ataxia World Together
PRO’S AND CON’S OF CANDIDATE
DRUGS FOR HUMAN TRIALS
• Rationale--do we expect it to work? Basic Science
• Efficacy-has it worked in well-designed
animal or pilot human trials?
• Safety-has safety been proven?
• Do the anticipated benefits outweigh the
possible risks?
• Availability--designer drugs vs. already
available ones. What’s in it for the drug
company?
• Cost (and where to get the money from)
March 17, 2011
NAF AMM LA CA Bringing the
Ataxia World Together
OFFICIAL PIPELINE FOR NEW DRUGS
Up to 15 years and $500-700million
to get to market
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Discovery—clinicians and
scientists working out the cause of
the disease, the “dominos” that fall
over, and targeted candidate drugs.
Preclinical testing—test tube and
animal studies.
Phase I—dosing, safety
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Phase II—safety, possible efficacy
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Phase III—efficacy
FDA Approval
Phase IV--Post-marketing studies
for long-term side-effects and good
effects.
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To help with promising drugs for serious
diseases with unmet needs:
NIH—Rapid Access to Intervention Development
(RAID)
FDA—Orphan Drug Status
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March 17, 2011
NAF AMM LA CA Bringing the
Ataxia World Together
FUNDING
A PUBLIC-PRIVATE PARTNERSHIP
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Discovery—clinicians and
scientists working out the cause of
the disease, the “dominos” that fall
over, and targeted candidate drugs.
$25-80,000 per yr over many years
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Preclinical testing—test tube and
animal studies.
$100,000 per year for at least 2 yr
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Phase I and Phase II-$500-700,000 per year for 4 yr
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Government
Private research foundations
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Government
Private research foundations
Pharmaceutical companies
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Government
Private research foundations
Pharmaceutical companies
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Pharmaceutical companies
$2-4 million to get to this point
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Phase III—$4-5 million ($10K/subject)
FDA Approval
Post-marketing studies for longterm side-effects and good effects
and possible other uses of the drug.
March 17, 2011
NAF AMM LA CA Bringing the
Ataxia World Together
EFFICACY--CAN WE SHOW THAT THE DRUG
ACTUALLY MAKES A DIFFERENCE?
• Symptomatic benefit vs. disease-modifying
• Is the candidate drug strong and specific?
• How much does the disease change over
how much time? Natural history.
• How accurately can this change be
measured? Rating scales, QOL measures.
• Can biomarkers show clinically meaningful
change quicker? 1° vs. 2° outcome measure.
• Can enough researchers and patients be
found? Research centers and registries.
March 17, 2011
NAF AMM LA CA Bringing the
Ataxia World Together
Neurobiological marker
Model for Clinical Trials
100
80
60
Diagnostic (motor) threshold
40
20
0
20
25
30
35
40
45
50
55
Age
CAG < 30
March 17, 2011
CAG > 39 Untreated
NAF AMM LA CA Bringing the
Ataxia World Together
CAG > 39 Treated