1. 0 Case Presentations: Research and Ethics Presenter

2. WWW.AAO.ORGAMERICAN ACADEMY OF OPHTHALMOLOGY Disclosures  The speaker has no financial interest in the subject matter of this presentation and is not representing the Ethics Committee of the American Academy of Ophthalmology with this presentation  For questions about the material contained herein or about the Academy’s ethics program in general, please contact the ethics program manager, Mara Pearse Burke at ethics@aao.orgethics@aao.org

3. WWW.AAO.ORGAMERICAN ACADEMY OF OPHTHALMOLOGY Code of Ethics Rule 3 – Research and Innovation  Research and innovation shall be approved by appropriate review mechanisms to protect patients from being subjected to or potentially affected by inappropriate, ill-considered, or fraudulent basic science or patient-oriented research.  Basic science and clinical research are conducted to develop adequate information on which to base prognostic or therapeutic decisions or to determine etiology or pathogenesis, in circumstances in which insufficient information exists.

4. WWW.AAO.ORGAMERICAN ACADEMY OF OPHTHALMOLOGY Code of Ethics Rule 3 – Research and Innovation  Appropriate informed consent for research and innovative procedures must recognize their special nature and ramifications. In emerging areas of ophthalmic treatment where recognized guidelines do not exist, the ophthalmologist should exercise careful judgment and take appropriate precautions to safeguard patient welfare.

5. WWW.AAO.ORGAMERICAN ACADEMY OF OPHTHALMOLOGY Case Presentation 1  Dr. J does not have any financial relationships with pharmaceutical or device companies.  He is interested in becoming involved in clinical research and perhaps even publish a few papers, as he has a busy clinical practice.

6. WWW.AAO.ORGAMERICAN ACADEMY OF OPHTHALMOLOGY Case Presentation 1  Dr. J does not have any financial relationships with pharmaceutical or device companies.  He is interested in becoming involved in clinical research and perhaps even publish a few papers, as he has a busy clinical practice.

7. WWW.AAO.ORGAMERICAN ACADEMY OF OPHTHALMOLOGY Case Presentation 1  Dr. J has performed 150 RapidBypass™ over the past 3 years and believes it would be interesting to compare the outcomes of this procedure with trabeculectomy.  A regional meeting is coming up in 6 months and the call for abstracts has just been sent.

8. WWW.AAO.ORGAMERICAN ACADEMY OF OPHTHALMOLOGY Case Presentation 1  The abstract of the retrospective comparison of these two techniques in 250 patients is accepted and Dr. Search presents a paper at the meeting.  She receives many accolades for her fine work and is encouraged by her colleagues to submit for publication.

9. WWW.AAO.ORGAMERICAN ACADEMY OF OPHTHALMOLOGY Case Presentation 1  She prepares a paper for submission to a major specialty journal and it is rejected…

10. WWW.AAO.ORGAMERICAN ACADEMY OF OPHTHALMOLOGY Case Presentation 1  Excerpt from letter from the editor: “…Your paper is being rejected for publication as your research did not undergo required review by an institutional or local Investigational Review Board. This is a requirement for all research published in our journal.”

11. WWW.AAO.ORGAMERICAN ACADEMY OF OPHTHALMOLOGY “Research” defined  Federal regulations definition  “…a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge.” NIH. Office of Human Subjects Research. Code of Federal Regulations, Title 45, Part 46. Protection of human subjects, subpart 102 (definitions)

12. WWW.AAO.ORGAMERICAN ACADEMY OF OPHTHALMOLOGY “Human subjects” defined  Individuals whose physiologic or behavioral characteristics and responses are the object of study in research  Living individuals about whom an investigator conducting research obtains: Data through intervention or interaction with the individual, or Identifiable private information

13. WWW.AAO.ORGAMERICAN ACADEMY OF OPHTHALMOLOGY Is this review really research?  Patient interviews  Follow-up contact of patients to determine the effectiveness of a program or a treatment  Chart review  Analysis of computer-stored clinical and administrative data  Mailed questionnaires  Randomized trials of experimental drugs, devices, and procedures

14. WWW.AAO.ORGAMERICAN ACADEMY OF OPHTHALMOLOGY Requirement of IRB review  Presentation at a scientific meeting  Publication in a scientific journal  Implication of intention to contribute to generalizable knowledge

15. WWW.AAO.ORGAMERICAN ACADEMY OF OPHTHALMOLOGY Variations in IRB regulations  Local vs. Institutional  “Exempt status” If research falls into specific category Example: Research involving the collection or study of existing data, documents, records, pathological or diagnostic specimens, if these sources are publicly available or if the information is recorded by the investigator in such a manner that subjects cannot be identified, directly or through identifiers linked to the subjects*  Expedited (minimal-risk) vs. Full board review

16. WWW.AAO.ORGAMERICAN ACADEMY OF OPHTHALMOLOGY Clarification of Existing Data  The term “existing” means that all of the data, documents, records, or specimens to be used in the research are in existence prior to IRB review and were collected for purposes other than the proposed research.  Principle = rights of individuals should be respected and participants should provide permission for their individually identifiable information to be used for research purposes.

17. WWW.AAO.ORGAMERICAN ACADEMY OF OPHTHALMOLOGY Privacy Issues: Authorized access to Protected Health Information  Extrapolation of HIPAA regulations to clinical research  Data or documents must either be available to the public or the data must be stripped of any direct (names, addresses, SSN) and any indirect identifiers (codes that can link data to participants)  De-indentified data review also may require IRB approval

18. WWW.AAO.ORGAMERICAN ACADEMY OF OPHTHALMOLOGY Similar case scenarios…  A university faculty member presents case studies to ophthalmology residents including patient images and facts obtained from existing patient files. Is IRB approval required?

19. WWW.AAO.ORGAMERICAN ACADEMY OF OPHTHALMOLOGY ANSWER  NO - This is not research as the lecture is not intended to provide “generalizable” knowledge and it is being presented at a “private” seminar to residents, not a public setting.  However, identifiable patient data must be removed for HIPAA compliance.

20. WWW.AAO.ORGAMERICAN ACADEMY OF OPHTHALMOLOGY What Do You Think?  A private practitioner is asked to present a case study at the local “Eye Study Club” meeting to his colleagues in the area.  Is IRB approval required?  Does publication of the case study in a journal require IRB approval?

21. WWW.AAO.ORGAMERICAN ACADEMY OF OPHTHALMOLOGY What Do You Think?  MAYBE….  IRB approval may not be required to present a case study at a meeting as the information is not generalizable…HOWEVER, case reports are not clearly regulated by the same federal mandates and IRBs may not consider them under their purview.

22. WWW.AAO.ORGAMERICAN ACADEMY OF OPHTHALMOLOGY Case Report Publications  Some journals require IRB review/regulatory approval prior to publication  Panda et al. (JAMA 2007) 22% of 124 medical schools considered a case report a form of research and required IRB review  Patient privacy/consent and risk management

23. WWW.AAO.ORGAMERICAN ACADEMY OF OPHTHALMOLOGY Case Presentation 2  Dr. B is a busy cataract and refractive surgeon in a major metropolitan area Private practice Clinical appointment at local teaching institution

24. WWW.AAO.ORGAMERICAN ACADEMY OF OPHTHALMOLOGY Case Presentation 2  Dr. B serves as a consultant and speaker for Stellate Surgical, the manufacturer of the Collimated IOL  Dr. B is asked by Stellate Surgical to participate in a FDA phase 2 trial of a phakic IOL

25. WWW.AAO.ORGAMERICAN ACADEMY OF OPHTHALMOLOGY Case Presentation 2  After signing a confidentiality agreement, Dr. B is provided with a Protocol Summary Inclusion criteria  Between 6.00 and 12.00 D of myopia Enrollment expectations  50 patients in a 12 month enrollment period Compensation  For each procedure performed, the facility fees are paid for by Stellate Surgical and surgeon is paid a $2000 professional fee  Each site paid $200-$400 for completion of pre-op and each of 8 post-operative visits

26. WWW.AAO.ORGAMERICAN ACADEMY OF OPHTHALMOLOGY Case Presentation 2  Site Feasibility Survey Dr. B is asked to provide an estimate of the number of patients seen in the previous 12 months who meet the inclusion and exclusion criteria A computerized search is performed to identify patients diagnosed with myopia who were not treated with keratorefractive surgery  Each patient’s chart was reviewed by a staff member to determine whether they met the inclusion and exclusion criteria

27. WWW.AAO.ORGAMERICAN ACADEMY OF OPHTHALMOLOGY Case Presentation 2  Clinical Trial Agreement Dr. B receives and reviews the CTA To increase the likelihood that potential patients will choose to enroll in the study, Dr. B requests that the patient compensation for study enrollment be increased, to which Stellate Surgical agrees

28. WWW.AAO.ORGAMERICAN ACADEMY OF OPHTHALMOLOGY Case Presentation 2  IRB Submission Stellate Surgical provides Dr. B with a copy of the study protocol, which he submits, along with a copy of his standard consent form for phakic IOL surgery, to the local IRB

29. WWW.AAO.ORGAMERICAN ACADEMY OF OPHTHALMOLOGY Case Presentation 2  IRB Response Numerous concerns regarding submission :  Proposed method of identifying potential subjects – Search using ICD-9 diagnosis of myopia and chart review  Proposed method of recruiting potential subjects – Scripts used for telephone recruitment interviews not submitted  No discussion of how potential for coercion to be avoided/minimized

30. WWW.AAO.ORGAMERICAN ACADEMY OF OPHTHALMOLOGY Case Presentation 2  IRB Response Numerous concerns regarding submission:  Patient compensation deemed excessive  No discussion of management of COI  Submitted ICF not appropriate for research study  HIPAA Research Authorization for Release of Personal Health Information for Research not submitted Dr. B’s IRB application should also be reviewed by the University’s COI Review Committee

31. WWW.AAO.ORGAMERICAN ACADEMY OF OPHTHALMOLOGY Recruiting Potential Study Subjects  Acceptable means of recruiting patients Direct recruitment  In person, on the phone or on the internet  Scripts used for in-person or telephone recruitment interviews require IRB approval prior to contact Public notices  Advertisements, flyers, information sheets, internet postings  Require IRB approval prior to posting Recruitment letter  Requires IRB approval prior to sending

32. WWW.AAO.ORGAMERICAN ACADEMY OF OPHTHALMOLOGY Recruiting Potential Study Subjects  Unacceptable means of recruiting patients Direct recruitment by study sponsors Use of incentives and referral fees

33. WWW.AAO.ORGAMERICAN ACADEMY OF OPHTHALMOLOGY Informed Consent Process  The process of obtaining informed consent must be described in detail in IRB submission  ICF for research study is distinct from ICF routinely used prior to surgery Consent given to have procedure performed as well as to participate in study protocol Disclosure of financial interest required

34. WWW.AAO.ORGAMERICAN ACADEMY OF OPHTHALMOLOGY COI Review Committee  Referral to COI Review Committee likely to occur when investigator has consulting relationship with or equity holding in the research sponsor Committee may recommend $10,000 annual cap on compensation during the course of the study Investigator may be asked to disclose financial interests on ICF

35. WWW.AAO.ORGAMERICAN ACADEMY OF OPHTHALMOLOGY What Do You Think?  Should professional medical organizations, like the AAO or the ACS, allow the presentation of research that has not undergone IRB approval?  If yes, should it be limited to a specific form of presentation, e.g., a poster vs. a verbal presentation?

36. WWW.AAO.ORGAMERICAN ACADEMY OF OPHTHALMOLOGY Resources  AAO Advisory Opinion, Research & Innovation  AAO Policy Statement, Identification and Resolution of Conflicts of Interest  AAO Advisory Opinion, Informed Consent