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 1 st and 2 nd 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 Apr 2:1-8. How Much Training Do You Get In Medical School/Residency/Fellowships? KU-Masters of Public Health NIH Institutional Training Grants CTSAs 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 elses 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 trialsBanking 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 interventionsPilot or feasibility studies Database queries that are designed to answer a research question Student research projectsguidance/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 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 dont enroll) Federal funded studies require all unused money to be returned You Want to Reach For the Stars Multi- Center 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? You Study Coordinator Project Manager Lab Tests Study Specific study events and the people to perform them Statistics Database Pharmacy Dont 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 staffs normal activities to mind the monitors that includes you) If you dont 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 Dont 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 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 IRBs prefer that you have funding in place before they review It is a time cost thing for them as well. Whats Next Building databases Creating forms Getting drug ready Writing the Manual of Operations Training the sites Start looking at your patient pool Cant 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 IRBs 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 didnt 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 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 wasnt 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 COULDNT DO THE STUDY Why Do Research? It will help the patient (isnt 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