Responsible Conduct of Research Providing credible, reliable data (PREP Course #7) November 15, 2011 350 Community Drive, Goldman Conference Center 9:00-10:30
CME Disclosure The North Shore LIJ Health System adheres to the ACCME s Standards for Commercial Support. Any individuals in a position to control the content of a CME activity, including faculty, planners and managers, are required to disclose all financial relationships with commercial interests. All identified potential conflicts of interest are thoroughly vetted by the North Shore LIJ for fair balance and scientific objectivity and to ensure appropriateness of patient care recommendations. Course Director, Kevin Tracey, has disclosed a commercial interest in Setpoint, Inc. as a the cofounder, for stock and consulting support. He has resolved his conflicts by identifying a faculty member to conduct content review of this program who has no conflicts. The Speaker, Cynthia Hahn has nothing to disclose.
Agenda/Goals Identify essential study records Describe principles of record keeping and study documentation Illustrate how to maintain records after study closure Identify Research Misconduct vs. Research Non-Compliance Identify and describe reporting mechanisms
What is RCR? Responsible Conduct of Research Data Acquisition, Management, Sharing and Ownership Conflict of Interest and Commitment Human Subjects Animal Welfare Research Misconduct Publication Practices and Responsible Authorship Mentor / Trainee Responsibilities Peer Review Collaborative Science
Record Keeping/Study Documentation Essential Documents = Research Data: Recorded information necessary to replicate, validate or reconstruct basic or clinical research findings. Financial Regulatory Source Raw Data Analyzed Data
Examples of research data can include: Field notes, completed questionnaires Data abstraction forms Laboratory notebooks Patient charts Cage cards Audio tapes, video tapes and electronic data files Gels, blots, spectra, samples, specimens IRB consent forms, research reports, analytical results, analysis Software (computer programs, computer databases and documentation thereof), and records of scientific or technical nature Printouts, computer disks Photographs, slides, negatives, films, scans, images, electrophysiological recordings Data contained in theses and dissertations and all other materials that are relevant to the research or sponsored project Preliminary data in grant applications
Why You Need Documentation If it s not documented, it never happened. Reasons: Proof of data collection Provides an audit trail for assessment and verification of study data quality Validates results Evidence of investigator compliance with GCP, regulations, and education requirements Documentation must be maintained regardless of sponsor/funding source
Audits and Inspections Who may be looking at your records? External Federal Agencies (e.g. FDA, OHRP, ORI, etc.) State Agencies (NYSDOH, ACS, etc.) Sponsors & monitors Journals Internal IRB & Office of Research Compliance Reviews Research Misconduct Reviews
Regulatory Background Federal Regulations: Common Rule (IRB) - 45 CFR 46 FDA regulations - CFR Title 21 Research Misconduct 42 CFR Parts 50 and 93 State Law Institutional & IRB Policies Good Clinical Practice (GCP) Guidelines ICH E6 Essential documents for a study
Applicable System Policies Research Data Ownership Maintenance, Storage, and Archiving Clinical Research Data Research Misconduct
Research Data Ownership Tangible and intangible research data, inventions, discoveries and devices developed at or through the use of Health System facilities or resources are the property of the Health System. Rights to such property may be transferred to third parties (such as sponsors) only with the express prior written authorization of the Health System. Each PI has principal responsibility for the custody of research data generated in his/her research and clinical studies, whether or not externally sponsored. Identifiable information generated as a result of participation in a clinical research study is Protected Health Information (PHI) under the Health Information Portability and Accountability Act (HIPAA). As a result all applicable health care privacy rules and regulations must be followed.
Data Storage, Access, and Management The PI is responsible for the recording, collection, management and retention of research data from any study or project, whether externally or Health System sponsored. These records should include sufficient detail to permit examination and replicate the research or project respond to questions that may result from unintentional error or misinterpretation establish authenticity, and confirm the validity of the conclusions.
Lab Notebooks Study title, Investigator s name(s) Study hypothesis, Detailed information on the materials used Sources of the materials Experimental methodology, Statistical treatments, results and conclusions so as to enable replication of the experiments by others at any time and to provide evidence of the creation of inventions. In the event that entry of such research data in an experimental notebook is not possible, the research data shall be secured and explicit instructions as to where the research data can be found (e.g. location of disks, samples, specimens) should be included in the notebook.
Good Clinical Practice (GCP) Created to establish a common standard for clinical research practice All studies are held to GCP standards E6: Guidelines for essential documents to be maintained by investigator and sponsor Before, during, and after the trial (see handout) Access ICH GCP E6 Guidance online: www.fda.gov/downloads/drugs/guidancecompliance RegulatoryInformation/Guidances/ucm073122.pdf
Research Data Management The Principal Investigator or must preserve clinical research data for a minimum of seven (7) years for adult subjects and (10) years for pediatric subjects after the final project closeout. When the clinical research study involves a FDA regulated product or device, all clinical research data associated with the trial must be maintained for up to two (2) years after a marketing application is approved; or, if an application is not approved, until two (2) years after shipment and delivery for investigational use is discontinued and FDA has been so notified as required by FDA regulations at 21CFR312.57. Where data supports a patent, such data must be retained as long as the patent and any derivative patents are valid;
Research Data Management Non-Clinical data must be maintained for at least 3 years after a project is completed. If allegations of scientific misconduct, conflict of interest, or other charges arise, data must be retained until such charges are fully resolved If a student is involved, data must be retained at least until the degree is awarded or the student has unambiguously abandoned the work; and Data must be retained if required by the terms of a grant, contract, Institutional Review Board (IRB) approval or other agreement, or applicable law.
Fundamental Elements of Data Quality Is your documentation ALCOA compliant? A Attributable Does the documentation clearly demonstrate: Who created the record and when, What happened, and When it occurred? L Legible Can the information be easily read and understood? C Contemporaneous - Was the information documented with timeliness? Complete Does the documentation include all of the necessary information? O Original Did you maintain the source of the information (see GCP Glossary, Sections 1.51 and 1.52)? A Accurate Does the information represent what actually happened? Adapted from - FDA - GUIDANCE FOR INDUSTRY - COMPUTERIZED SYSTEMS USED IN CLINICAL TRIALS - ALCOA http://www.fda.gov/downloads/iceci/enforcementactions/bioresearchmonitoring/ucm133749.pdf
Attributable Ensure that the documentation: Clearly describes who the documentation is about. Demonstrates who is involved in the event. Demonstrates the rationale for any revision in the data as well as who made the revision. Legible Ensure that written notes can be easily read and understood. Contemporaneous Ensure that the information was documented with timeliness. When information is added later this weakens its credibility. Complete Ensure the documentation includes all of the necessary information. Original Ensure the source is maintained and available. Accurate Ensure that the documentation captures what actually happened. Explain discrepancies. 18
Authorship Authorship credit should be based on 1) substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; 2) drafting the article or revising it critically for important intellectual content; and 3) final approval of the version to be published From: ICMJE: Uniform Requirements for Manuscripts Submitted to Biomedical Journals: Ethical Considerations in the Conduct and Reporting of Research: Authorship and Contributorship
Research Misconduct Fabrication, falsification or plagiarism in proposing, performing or reviewing research or in reporting research results. Research misconduct does not include honest error or differences of opinion.
Misconduct Fabrication making up data or results and recording and reporting them. This may also include misrepresentation of a researcher s qualifications or ability to perform the research in grant applications or similar submission. Falsification manipulating research materials, equipment or processes, or changing or omitting data or results such that the research is not accurately represented in the research record Plagiarism the appropriation of another person s ideas, processes, results or words without giving appropriate credit.
Policy on Misconduct All employees or individuals associated with the North Shore-Long Island Jewish Health System must report observed, suspected, or apparent misconduct in research to the Research Integrity Officer, any Institutional Official, the Office of Research Compliance, or via the Corporate Compliance Help Line 1-800-894-3226. Any employee who reports such information will be protected against retaliation for making the report.
Research Misconduct Case #1 An investigator is working on a multicenter project with collaborators at 5 other institutions and decides to submit a grant to NIH on a related topic. In his grant application he analyzes partial data from his site that was collected as part of the larger project in support of the new application. Since the data he analyzed was only from his site, he does not discuss the larger project or his collaborators role. Is this research misconduct, why or why not?
Case #2 Dr. Clean is conducting an investigator initiated clinical trial. Dr. Smith is a colleague at the same institution who refers patients to Dr. Clean s study and occasionally conducts study related treatments. Dr. Smith is listed on the IRB application on a subinvestigator, but does not participate in protocol development and analysis. When Dr. Clean publishes the study he does not list Dr. Smith as an author. Is this Research Misconduct, why or why not?
Case #3 Dr. Brown is working in the lab when he notices that all his samples are being destroyed by the reagent he is using, so he switches the reagent during the next experiment, since this worked better he continues to do it. Is this Research Misconduct, why or why not?
Case #4 Dr. Brown is working in the clinic when he notices that it appears all of the subjects on a study are having a skin reaction to a cream being used in testing. The cream itself is not the test article being evaluated in the study so he switches the cream during the next test and the next group of subjects does not have a reaction, since this worked better he continues to do it. Is this Research Misconduct, why or why not?
Case #5 Post doc A and Post doc B are working on a project together. During the analysis two data points don t make sense and seem to be errors. Post doc B argues they should just delete the two data points from the analysis, arguing that the samples that day must have been contaminated. Is this Research Misconduct, why or why not?
Case #6 An investigator is conducting PCR analysis and the images seem fuzzier than usual. She scans the results into her computer and uses photoshop to change the contrast making the results easier to see. She does not think this should be a problem since she making the change across all the results. Is this Research Misconduct, why or why not?
Resources Policies are on Healthport Research Integrity Officer: Dr. Bettie Steinberg 516-562-1159 Research Compliance: 516-562-2018 Web-Based Reporting www.northshorelij.ethicspoint.com Available 24 hours, 7 days a week Reports Can Be Made Anonymously