Introduction to Clinical Research


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  • Research:~ databases used for QA are not to be used for research~ just gathering stuff in a excel sheet is the systematic collectionHuman subject~ the vast majority of dataset you engage with here are going to have a mix of living and deceased subjects. Therefore they require IRB approval. Even if they are all deceased, you need to submit to the IRB for an exemption ~ biospecimens when linked with ANY clinical data are definitely human subjects researchDefinition of Key Research Personnel:~ named on a grant~ lab people using the specimens~ statisticans~ medical students~ those named on the abstract/paper
  • Regulatory compliance (current review board approvals, correct version of documents used, etc)AuditsTRIGGERED BY time study open, level of risk, investigator, reports of misconduct, high enrollment, FDA submission)Look at Deviations. Two categories:Major deviationsImpact subject safety or alter the risk/benefit ratioCompromises the integrity of the study dataImpacts subjects willingness to participate Should be reported within 10 business daysMinor deviationsDoes not impact subject safetyDoes not compromise integrity of the study dataDoes not affect subject willingness to participate Summarized at the time continuing renewalExcess minor deviations can add up to a major deviation or be justification for closing the study
  • From all of the sites involved in the study study must be reviewed by all participating sites and have documentation of that review—even if its just exempt specimens processed at MD Anderson stats done at UNCProcess not properly documented signing of form, description of conversation in clinic noteloseing the consent formNot all subjects in prospective database consented if the subjects arent consented, we cant use them at the time of analysis means: all subjects have to be screened in your dataset holes in dataset Consent form not properly completed filling in ALL of the little holes. If there is a space, it must be filled in. or else it’s a deviationDeviating from the scope of protocol question asked of the data not covered by the protocol collecting followup information from sources not listed in the protocol
  • University policy for reporting Sponsor’s policies varyIf you think there is an unanticipated problem or serious adverse event, contact Kim or meunexpected (in terms of nature, severity, or frequency) related or possibly related to participation in the research reasonable possibility that the incident, experience, or outcome may have been caused by the study agentHospitalization virtually always requires reporting to at least the sponsor
  • FDA Can shut down entire research institutions—UIC-rereviewed every single protocol
  • preempting common issues ("ididnt know i needed IRB approval", ididnt know i/they werent named on the protocol, ididnt know icouldnt share the data with northwestern/UCSD/sloankettering/duke,etc, ididnt know that wasntwthin the scope of the protocol, all the holes on the consent werent filled in, ididnt know i needed IRB approval from UIC/Silvercross/sherman, collaborations with other departments)
  • ~ how to do your own project ~We need to keep tabs on all of the projects going on in our dept, less we be executed by the office of clinical research, cancer center, office of clinical research, department of health and human services, FDA, medical liscensing boards, journals ~ Can assess if it falls under the scope of an existing protocol and therefore not require more than an IRB amendment~ Help with initial design of study, ~Will put you in touch with a statistican~ Funding, collaboration, support staff consideration~ Review of study prior to CTRC submission, which does a scientific review of the study (was on the committee as a full member, now does radiation review)
  • Completing CITI Research Training refresher training required if done more than 3 years agoFeel free to come to our weekly RadOnc Clinical Research Meeting and DSMB on Fridays at 1130am in the conference room learn about our active projects, common issues in clinical research administration, ask questions! there is often foodContact us early regarding ASTRO projects study approval process is slow 3 months for a new protocol 1 month for an amendment forever for multi-institutional plus data requests for followup, etc
  • Introduction to Clinical Research

    2. 2. ROLE OF RESIDENTS IN CLINICAL RESEARCH • Ways residents engage in clinical research • • • • • Consent subjects to research databases Screen patients Write their own protocols with a faculty sponsor Perform retrospective analyses Engage in translational research
    3. 3. WHAT IS HUMAN SUBJECTS RESEARCH? • Research • Research means a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge. 45 CFR 46.102(d) • Human Subject • Human subject means a living individual about whom an investigator (whether professional or student) conducting research obtains data through intervention or interaction with the individual, or identifiable private information [about]. 45 CFR. 46.102(f) • Key Research Personnel • Persons who have direct contact with subjects, contribute to the research in a substantive way, have contact with subjects’ identifiable data or biological samples, or use subjects’ personal information
    4. 4. EXAMPLES OF HUMAN SUBJECTS RESEARCH • Collecting samples of body fluid or tissue • Implanting or using a device • Recording information that is not routinely collected in the course of treatment • Administering a drug or new combinations of therapy • Administering RT at non-standard doses or in non-standard ways • Evaluating a diagnostic technique • Interviewing, surveying or observing human subjects • Reviewing medical records • Reviewing already collected specimens
    5. 5. REGULATION OF CLINICAL RESEARCH • HIGHLY regulated area • HHS’s Office for Human Research Protection (OHRP) • FDA • CMS • Enforced through audits and site monitoring visits • That evaluate: • • • • • Compliance with the protocol Informed consent Documentation of study procedures Adverse event reporting Regulatory compliance • Internally by • Evaluations are conducted: • • • • Office of Clinical Research Comprehensive Cancer Center Institutional Review Board (IRB) • • • • Sponsor (RTOG, Alliance, PhRMA/Device Company, Investigator) Data and Safety Monitoring Boards OHRP FDA Externally
    6. 6. COMMON RESEARCH DEVIATIONS • Not having proper committee approval • Including initiating of research prior to IRB approval • Review letters not available from all sites involved in the study • Not properly obtaining consent • • • • Consenter not named on the protocol Process not properly documented Consent form not properly completed Not all subjects in prospective database consented • Not properly documenting study elements • Consent process • Required study evaluation (e.g. performance status) • Documentation of review of medications • Deviating from protocol specifications • • • • Evaluation performed outside of study window Deviating from the scope of protocol Subject does not meet all of the eligibility criteria Engaging in a study specific procedure prior to consent
    7. 7. COMMON RESEARCH DEVIATIONS • Unanticipated Problems not reported per institutional requirements • Must be reported within 10 days if three elements are met: • unexpected (in terms of nature, severity, or frequency) given (a) the research procedures that are described in the protocol-related documents, such as the IRB-approved research protocol, investigator’s brochure, drug or device product information, informed consent document, or other research materials; and (b) the characteristics of the subject population being studied, including underlying diseases, behaviors, or traits; • related or possibly related to participation in the research (possibly related means there is a reasonable possibility that the incident, experience, or outcome may have been caused by the procedures involved in the research); and • suggests that the research places subjects or others at a risk of unknown harm or addition/increased frequency of harms(including physical, psychological, economic, legal, or social harm) than was previously known or recognized.
    8. 8. PENALTIES FOR RESEARCH NONCOMPLIANCE • Academic Journals • Will not publish research without valid IRB approval • FDA will not accept data from subjects or sites with significant deviations publishes their findings of noncompliance Can ban investigators from engaging in further research maintains a publically accessible list on their website of “Disqualified/Totally Restricted List for Clinical Investigators” • Can shut down entire research institutions • • • • • Academic Centers • Sanctions against investigators • Can shut down studies or entire research programs • NCI • Suspension of medical practice • Medical Board • Issue sanctions, including loss of license
    9. 9. OTHER REVIEW COMMITTEES • Radioisotopes and Radioactive Drugs Research Advisory Committee(RADRAC) • Reviews radioactive drugs as well as the purchase and use of radioisotopes in humans • Approval generally not required in human subjects research • Nursing Research Committee • Institutional Biosafety Committee (IBC) • Reviews biohazards, as defined as potentially infectious agents, organisms or materials, biological toxins, organisms containing recombinant DNA and other genetically altered organisms and agents, in laboratory and clinical settings. • Institutional Animal Care and Use Committee
    10. 10. COMMON QUESTIONS ABOUT CLINICAL RESEARCH • Collaboration with other institutions • Study must be reviewed by all institutions involved • Most require data sharing or material transfer agreements • Case Reports • Requires project specific consent, but not IRB approval • Copies of protocols and consents • • IRB Exemptions • Still require an IRB submission • Prospective research databases • If patients are not consented, their data cannot be used in the analysis
    11. 11. HOW DO I DO MY OWN PROJECT? Think about what you want to do for 30 minutes, then Email
    12. 12. KEY ELEMENTS OF A PROTOCOL • Background and Study Rationale • Objectives • Phase • Measurements of objectives • Criteria for response, study success • • • • Eligibility/Exclusion Criteria Treatment Plan Monitoring of Subject/Visit Schedule Adverse Event Procedures • • • • Statistical Considerations Data Collection Forms References Study Consent • Dose Reduction Plan • Off-Study Criteria
    13. 13. REQUIREMENTS TO ENGAGE IN CLINICAL RESEARCH • Completing CITI Research Training and Conflict of Interest Statement (COI) • • Amending the IRB submission to include you as a researcher