Transcript so you think you want to do research, huh?

SO YOU THINK YOU WANT TO DO
RESEARCH, HUH?
Laura Herbelin, Research Instructor
University of Kansas Medical Center
02/05/2016
How Much Training Do You Get In Medical
School/Residency/Fellowships?
• At KUMC, can do 8 weeks of research between 1st
and 2nd year
– Neurological and Rehabilitation Sciences Training
Program
– Summer Research Training Program (SRTP)
• Macchi Z, Wang Y, Moore D, Katz J, Saperstein D, Walk D,
Simpson E, Genge A, Bertorini T, Fernandes JA, Swenson A,
Elman L, Dimachkie M, Herbelin L, Miller J, Lu J, Wilkins H,
Swerdlow RH, Statland J, Barohn R; Western ALS (WALS)
Rasagiline Study Group. A multi-center screening trial of
rasagiline in patients with amyotrophic lateral sclerosis:
Possible mitochondrial biomarker target engagement.
Amyotroph Lateral Scler Frontotemporal Degener. 2015 Apr
2:1-8.
How Much Training Do You Get In Medical
School/Residency/Fellowships?
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KU-Masters of Public Health
NIH Institutional Training Grants
CTSA’s offer training
But realistically, most training is accomplished
‘on the job’
• As a student, resident or fellow
– How much time to you have to devote to research
You Want To Do Research
• Questions you should ask yourself
– My research or someone else’s
• Can this be done by data-mining (retrospective chart
review)
• Do I need to start from scratch
What Is The Next Step?
How Much Time?
• Type of studies:
– Case series and case reports
– Randomized controlled studies
– Double-blind method
– Meta-analyses
– Systematic Reviews
Case Series and Case Reports
• Single or multiple patients
• No control group
• Benefits of case series/reports
– Easy to understand
– Accomplished very easily
What Is The Next Step?
Submission to Internal Review Board
(IRB)
• As a student, resident or fellow
– Utilize your University IRB
• Practicing physician
– University – probably no cost to minimum cost
– Private Practice
• Central IRB
--------But Wait------
• Does your study need IRB (HSC) review?
Clinical trials
Banking of tissue, blood, specimens
for future research
Research involving surveys,
interviews or focus groups
Research on educational practices
Collection of data obtained from
clinical procedures
Retrospective chart reviews
Research on behavioral interventions Pilot or feasibility studies
Database queries that are designed
to answer a research question
Student research projects
www.kumc.edu/documents/hrpp/topical guidance/activities that require
HSC review.pdf
--------But Wait-----• According to KUMC HSC website
– Case reports or case series needs prior approval from the HSC
• A report of a small number of cases (generally not more than three),
is not considered human subjects research, provided that:
– 1. the report is compiled by persons already involved in patient's care;
– 2. the information is presented/published in de-identified form;
– 3. no changes were made in the patient's care or diagnostic testing for the
sake of reportability.
• Case reports may become human subjects research, or may have
other compliance requirements, if the above three stipulations are
not met, or if multiple cases are analyzed in a manner that tests a
hypothesis.
• NEED TO BE AWARE, WHAT ONE HSC MAY ADHERE TO AS
FAR AS POLICY DOES NOT MEAN THAT EVERY HSC WILL GO
ALONG
What type of submission
• What type of submission are you going to use
– Exempt (4 pages)
• Low risk educational research, anonymous surveys,
identifiable surveys on benign topics
– May use a letter of introduction, fact sheet or introductory
paragraphs on the survey itself instead of a consent form.
– Retrospective Protocol- Combined protocol and
application – at KUMC but not at every site (5
pages)
• No consent requirements as long as specimens must be
on the ‘shelf’ at the time of IRB submission
What type of submission
– Expedited Review (10 pages)
• Retrospective chart reviews that use a linking list
– Qualify for a waiver of consent
• Prospective registry of clinical data
– Written consent
• Focus groups and interviews
– Full Review (13 pages)
• Clinical trials
• Behavioral interventions
– Written consent needed
– Quality Improvement Determination
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Chart reviews to determine if clinical guidelines are being followed
Interventions to implement professional standards
Interventions to improve patient care
Needs assessments
– No consents needed
What can you not forget?
Cannot forget???
• Health Insurance Portability and
Accountability Act of 1996 (HIPAA)
– If project involves health information, additional
statements about HIPAA protections must be
included.
• Some sites require a separate document
Other Considerations
• Time to complete submission forms and
consent forms
• Whose is going to do statistics?
• Whose is going to build your database?
• Who is going to go back through charts to
obtain the data
• IRB may come back with questions
Show Me The Money
• May be able to get funding to offset the cost
of this study
– Have to have someone to manage the money
• Accountability
What Happens With No
Accountability?
Thinking Big
• Randomized, controlled trial
Considerations
• Do you want to be the primary site (the big
cheese, head honcho, the boss)?
• Do you want to be one of the worker bees?
– Just starting out – suggest being one of the worker
bees.
• Networking
• Grasp a better understanding of how multi-center studies
work
• If you try to get into pharmaceutical studies, you can build a
reputation and a research nest-egg
– Pharmaceutical studies usually will not ask for the money back
(unless you don’t enroll)
– Federal funded studies require all unused money to be returned
You Want to Reach For the Stars – MultiCenter Randomized Controlled Trial
• What do you want to study?
• If conducting a study with drugs
– How will you get drug – who is going to pay for it
• Some Pharmaceutical Companies may be able to provide
drug
– Can they provide placebo?
• Most University Pharmacies do not have the legal capability
to ship drug across state lines
– Have you discussed with your peers
• Benefit of networking
• If no one is interested, how will you recruit the patients
Multi-Center Randomized Controlled
Trial
• Who will you get to help you by being a site
– Your friends may not be the best choice
• Another advantage of starting as a worker bee in a study – you will learn who
is good at recruiting, creating the least mistakes, easy to work with
– Sometimes it is not your friends
• Do you need an IND?
– What is an IND – Investigational New Drug
– When is it needed?
• Conduct a clinical investigation with that is subject to 312.2(a)
• Submit an IND if any exempt criteria are not met
• Also certain FDA and NIH grants require an IND
– What is needed by FDAIND
• A protocol
• 1571, 1572
• Biosketch
Money
• Nobody does multi-center trials for free
anymore
– Place of employment may nix your participation
due to lack of money
– Need to consider who may fund the study
• Based on the amount requested – need to build your
study around that amount
– May not be the best time to try to obtain every bit of
information you want
Who Do You Need To Pay?
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You
Study Coordinator
Project Manager
Lab Tests
Study Specific study events and the people to perform
them
Statistics
Database
Pharmacy
Don’t forget the sites
– Have to account for indirects for not only your site but your
other sites
What Do You Have To Pay?
• Travel for your participants
• Monitors (time away from your staff’s normal activities to
mind the monitors – that includes you)
– If you don’t meet with them, you will get a ‘nasty’ note back
• Telephone calls to ensure that all sites are recruiting –
includes time
• If you obtain a grant from FDA – they funding agency will
come to see you
– You pay for the extra time it takes for your study coordinator to
get everything together and your time as well
• Some sites are requesting that we pay for monitor time at
their sites
What Does That Leave You?
• Headache because sites still want to be paid
when they are not working
• Empty pockets because there is never enough
money
– Choose study measures well
– Remember you budgeted for an amount and by
the time you obtain funding, it has increased
You Are Moving On With This Study
• You will need to apply for funding
– What funding is best for you disease?
– Should have conversations with the funding agency?
• Sometimes they can be helpful but no guarantee
– NIH – you have 2 attempts for the money
• So when they reject you on the first submission
– Don’t take it personally, they normally do
– Read comments and be sure to answer them on the next go round
– FDAOPD – can keep going back as many times as you want
• Just remember, the funding will take a good 1 ½ yrs to
come through
Once Funded
• Then you submit your protocol to HSC (IRB)
– Normally FDAIND regulatory and funding agency
will request changes
– Remember once you change the protocol, you
have to resubmit the updated protocol with list of
changes to both IND regulatory and the funding
agency
• Then you wait for approval
So I Know You Are Going To Ask This
Question
• Why not go ahead and submit to your IRB
while you are waiting for funding
– Most IRB’s prefer that you have funding in place
before they review
• It is a time cost thing for them as well.
What’s Next
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Building databases
Creating forms
Getting drug ready
Writing the Manual of Operations
Training the sites
Start looking at your patient pool
– Can’t tell them much
Then You Get the IRB Review Back
• They put your study on hold – they have
questions
• So you answer and Wait
– In the meantime, you change the forms you
worked on, you change the database to match the
forms, you rewrite the manual of operations
Yeh! – Its Approved
• Send the updated protocol to the FDAIND
regulatory and funding agency.
– By the way have you been keeping up with your
Quarterly Reports for the funding institution?
(NIH/FDA)
• You send the sites the new and approved
protocol and your IRB approval
– Then you wait and then answer the questions
each of the other sites IRB’s have
In the Meantime
• You can begin enrolling
– Good to enroll 1 patient quickly before you forget
what you are supposed to do but also to work out
as many bugs as possible before everybody else
comes on board.
– Where did all of the
patients go who offered
to participate? – Start
hunting
At the Same Time As the Sites Submit
To Their IRB
• Get the Lawyers involved at each site. You
have to have contracts.
– You will become good at ‘Playing Chicken’. Vegas
odds as to which lawyer will give in first
• So now its solved – all contracts are signed.
• Know the training you did earlier
– New personnel at your site and other sites, have
to start over
Up & Running
• Have to monitor that all sites are recruiting
– May have to be a pest
• Have to assure that all sites are conducting the study
correctly
– Are you prepared to throw your weight around
– Remember it is your name on the funding
• You are responsible – that is what the signed 1571 will tell you
• Oh, I didn’t tell you that you have to list your study on
clinicaltrials.gov website – you have to keep it up to
date.
– Not as easy as you may think
Study is Going
• Just keep on top of things and be flexible
– Situations will arise that you never would have
believed
• You may run into a drug shortage if you have to resupply the
drug
– Why not get enough medication at the beginning
» Most drugs donated expire after 1 to 1 ½ yrs
• Communication, Communication,
Communication is the key
• Remember you have to keep up with the
quarterly reports and the yearly progress reports
– So much paperwork
Study is Over
• You have to clean up the data
– You thought everybody entered all of the data
• Yah right
• You have to get people to enter data or why it wasn’t done
– New staff? May not be able to get the answer.
– You give the data to the statistician
– You get the results – you write the paper
– It is rejected. On to the next journal
• You have to change the format
• This time not rejected but needing rewrites
• Send it back and wait
• Finally published
Its Over – Not Quite
• Still have to enter the results into
Clinicaltrials.gov
– They come back and want changes
– Make the changes
• NOW ADD TO YOUR CV, BIOSKETCH, WORK
WEBSITE – SEND COPIES TO YOUR FAMILY, TO
THE NAYSAYERS WHO SAID YOU COULDN’T DO
THE STUDY
Why Do Research?
• It will help the patient (isn’t that why you
went into medicine)
• Prestige – you are published
– You need this for your career advancement
• You love the challenge
– You are not doing it for the money – at least not in
Neuromuscular
• And when you get your first positive study
result