Comprehending Research Misconduct and Malfeasance Peter H. Abbrecht, M.D., Ph.D. Medical Expert Office of Research Inte

1. Comprehending Research Misconduct and Malfeasance Peter H. Abbrecht, M.D., Ph.D. Medical Expert Office of Research Integrity

2. Why be concerned about prevention of research misconduct?

3. What is research misconduct?

4. (c) Plagiarism is the appropriation of another person�s ideas, processes, results, or words without giving appropriate credit. (d) Research misconduct does not include honest error or differences of opinion.

5. Requirements for findings of research misconduct There must be a significant departure from accepted practices of the relevant research community. and The misconduct must be committed intentionally, knowingly, or recklessly. and The allegation must be proven by a preponderance of the evidence.

6. Not all allegations of �misconduct� in clinical research meet the definition for �Research Misconduct� The distinction between research misconduct and other problems (such as protocol violations or fiscal malfeasance) is important because (a) institutions have different mechanisms for handling the different situations (e.g.inquiry/investigation research misconduct process vs IRB oversight and corrective actions for protocol violations) (b) reporting requirements (to oversight agencies such as ORI, OHRP, FDA, sponsors, etc) are different

7. Examples of Falsification Substituting one subject�s record for that of another subject Altering dates and results from subject�s eligibility visits Altering results of laboratory tests Backdating test or interview dates to fit protocol time window

8. Examples of Fabrication Creating records of interviews that were never performed Making up progress notes for patient visits that never took place and inserting them into the medical record Preparing records for calls and follow-up contacts for participants who had already died

9. IRB, OHRP, FDA issues that are not research misconduct(in the absence of falsification/fabrication): Failure to report adverse event to IRB/sponsor Protocol deviations (entering ineligible participant or using off-protocol drug) Forging physician�s signature on orders Failing to obtain or properly document informed consent Breaching human subject confidentiality

11. Some illustrations of instances of falsification or fabrication in clinical records from cases with PHS findings of research misconduct

12. Circumstances That Led to Misconduct Detection in ORI Cases

13. Lessons From ORI Clinical Cases Any person involved in clinical research may be responsible for scientific misconduct, regardless of rank or duties on the project The majority of respondents in ORI clinical cases are in technical positions (not doctoral degree holders) Many of these respondents worked with inadequate supervision or training Respondents may have had excessive work loads or time pressure or pressure to enroll subjects

15. Common areas of F/F include: protocol entrance criteria(date, lab, history) biased randomization assignments �filling in� missed data � f/u visits, etc. Interview protocols are at high risk for misconduct, especially if single interviewer and/or lack of adequate quality assurance Both scientific misconduct and violations of human subjects� protection may occur in the same clinical activity In such cases all oversight agencies involved (ORI, OHRP, FDA, IRB�s, etc.) work together

16. Suggestions for Preventing and Identifying Scientific Misconduct The P.I., Lab director, etc. must establish a climate in the lab in which scientific integrity (and the reasons for it) are emphasized All staff must be thoroughly trained in integrity principles and in conducting their portion of the protocol The P.I. and other supervisors must maintain strong communication with staff and a �presence� in the study setting, verifying personally at least a sampling of the research records

17. Staff should be questioned about data alterations in the research record (overwrites, erasures, whiteouts, changes in electronic records) If possible, in interview studies request informed consent to recontact the patient for quality control reasons, and follow up with a sampling of these patients Keep staff work loads reasonable Protocols should be designed with realistic requirements that can be met by both staff and patients

18. Protocol research forms should be as simple as possible, yet with clear designation of the required information In continuing studies, if possible, train more than one staff member to do follow-up

19. Any alterations on data forms must be done by striking through the original entry (no whiteout or writing over) and initialing and dating the new entry Copies of all laboratory reports should be retained by originating facility (to be spot checked on routine and special audits) Protocol sponsors should attempt to avoid paying bonuses based on number of patients enrolled

20. PARTIAL LISTING OF INVESTIGATOR COMMITMENTS FDA Form 1572(for studies requiring FDA approval)

21. Detecting and Handling Possible Scientific Misconduct in Clinical Research On routine audits, be alert for possible clues of F / F on clinical records (white outs, overwritten data, numbers out of physical alignment, errors in form completion) Prompt sequestration of records if suspicion/allegation of scientific misconduct

22. ORI Guidelines for Handling Allegations of Scientific Misconduct in Clinical Research (currently in draft form) ORI can provide assistance to institutions assessing possible scientific misconduct through its Rapid Response Technical Assistance (RRTA) program