Scientific Misconduct September 15, Presented by May Al Kassar

Transcription

1 Research Non-Compliance & Scientific Misconduct September 15, 2010 Presented by May Al Kassar

2 Responsible Research Conduct The ethical conduct of research is a shared responsibility among: The institution Agencies sponsoring research Investigators The research teams IRB members and staff

3 Role Of the IRB The IRB is the administrative body responsible for assuring that all parties involved in human subjects research activities are guided by the principles of the Belmont Report.

4 Definition of Non-Compliance Noncompliance: Any failure to follow: (a) (b) (c) (d) Provisions of an IRB-approved research study Institutional policies Local laws or federal laws (for federally-sponsored research) The requirements and determinations of the IRB Noncompliance can be categorized as non-serious (minor), serious, or continuing noncompliance. Noncompliance may pertain to the Principal Investigator (PI), the PI s research team.

5 Definition of Serious Noncompliance Serious Noncompliance: Any failure to comply with regulations that: (a) creates an increase in risks to research subjects (b) adversely affects the rights, welfare and safety of the research subjects and/or (c) adversely affects the integrity of the University s HRPP

6 Examples of Serious Noncompliance Failing to obtain informed consent from research participants Starting and/or completing research under a protocol before meeting the conditions required by the IRB and receiving IRB notification of approval Providing inadequate supervision of research that involves potential risks to subjects Implementing changes to a research study without obtaining prior IRB approval

7 CON T Failing to recruit participants according to the inclusion/exclusion criteria, or recruiting more participants than what was previously approved by the IRB Recruiting participants in the research study whose approval has already lapsed or the study has been suspended or terminated Failing to report or review serious adverse events and/or unanticipated problems to the IRB Failing to act on recommendations communicated by the IRB Office

8 Definition & Examples of Non-serious (minor) noncompliance Non-serious (minor) noncompliance: Noncompliance that does not affect the rights and the welfare of the research participants or put them at risk of harm. It also does not affect the integrity of the University s HRPP. Examples: Introducing minor changes or deviations to an IRB-approved protocol Using an approved, but non-irb stamped, consent form Failing to respond to official correspondence ( , letter) from the IRB Office which does not compromise the welfare of the research participants Not including dates of pt. consenting on ICF itself (but the date of visit documented in study log sheet)

9 Definition & Examples of Continuing Noncompliance Continuing Noncompliance: Repeated failure to understand and consistently comply with AUB IRB policies Examples: Repeated failure to comply with continuing review requirements Multiple recurrent problems with noncompliance with the same PI over a lengthy period of time, or The PI has a problem with multiple existing or previouslyapproved studies

10 Reporting of Noncompliance Any minor, serious or continuing noncompliance observed or suspected by individuals should be reported to the IRB Office. Reports can be submitted by the Principal Investigator (PI) via Self-Reporting, or by any other source via telephone, e- mail, or letter to the IRB office.

11 What happens after reporting noncompliance? If the event is determined to be minor noncompliance, the IRB Chair/Vice Chair will direct the IRB Officer/Administrator to make every effort to correct the issue (s) at the administrative level, in conjunction with the PI. If the event is considered to involve serious noncompliance or continuing noncompliance, the IRB Chair/Vice Chair will initiate an Inquiry/Investigation. Inquiry/Investigation This is a fact-finding process that may involve review of research records, research data (both published and unpublished), informed consent/assent forms, interviews with associated researchers, research assistants, students, and/or direct correspondence with the PI.

12 CON T Following an Inquiry and/or Investigation, determination by the IRB as to whether noncompliance has occurred and what corrective actions, if any, will take place. Corrective actions may even be recommended where there is a determination that there was no noncompliance, if the conduct of the human research could be improved and subject safety enhanced if certain actions were taken.

13 Spectrum of IRB Determinations for Corrective Measures Approve continuation of research without changes Develop a corrective action plan (for minor noncompliance only). The plan may include, but is not limited to, the following: Additional training and education of the PI/research team Additional supervision of PI Limiting research activities of the PI Limiting the number of enrolled participants Require modifications to the protocol Revise the continuing review timetable

14 CON T Modify the consent process Modify the information disclosed in the consent document Provide additional information to current &/or past participants Require that current participants re-consent to participation Require additional training of an investigator and/or study staff Reconsider approval Monitor the research Monitor the consent process

15 CON T Suspend IRB approval for one or more of the PI s studies until proper modifications to the study protocol under scrutiny are complete Terminate IRB approval for one or more of the PI s studies Recommend further administrative action to the University Recommend further reporting to federal agencies and department heads, as required under the FWA Disallow use of data and/or deny confirmation of IRB approval for publication submissions, in cases where data were gathered in research determined to be noncompliant Conduct announced and/or unannounced audits of this project (or any of this PI s protocols)

16 New Unit: Quality Improvement Program/Research Compliance The QIP/RCU is charged with evaluating and enhancing human research protections through monitoring and coordinating education and training with the Research Education Unit of the HRPP. The QIP/RCU conducts periodic spot audits, as well as for-cause assessments as directed by the IRBs, the HRPP Director or the Institutional Official (IO). New Policies pertaining to: Noncompliance and Allegations of Noncompliance Quality Improvement Program (QIP) Monitoring and Auditing Scientific Misconduct New IRB website

17 Death of a Normal Volunteer An Asian American student at the University of Rochester responded to an advertisement for a study March 31, 1996 undergo bronchoscopy for the harvest of alveolar macrophages The bronchoscopy was difficult and required numerous doses of topical lidocaine. The subject returned to the hospital in cardiac arrest from an overdose of lidocaine and died April 2, An investigation into this death revealed: The protocol did not limit lidocaine doses. The doses were not documented. The subject was not observed after the bronchoscopy. The concentrations of lidocaine were increased without IRB approval.

18 Death on Gene Therapy Trial In the fall of 1999, an 18-year-old Jesse Gelsinger died as a result of his participation in a gene transfer trial. Jesse had a rare metabolic disorder, ornithine transcarbamylase deficiency syndrome (OTC) that was being controlled by medication and diet. Researchers were testing an innovative technique using adenovirus gene transfer. Shortly after treatment, Jesse Gelsinger experienced multiple organ failure and subsequently died. Serious concerns related to the integrity of research with human subjects : Conflict of Interest Data Safety Monitoring Informed Consent

19 The Challenges Continue. New challenges of violating the norms relating to honesty and objectivity in research are coming up: Scientific misconduct : "fabrication, falsification, or plagiarism" (or FFP) Conflicts of Interest

20 Definition of Scientific Misconduct NIH defined Research misconduct as fabrication, falsification, or plagiarism in research. Fabrication is making up data or results and recording or Reporting them. Falsification is 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 is the appropriation of another person's ideas, processes, results, or words without giving appropriate credit.

21 Allegation of Scientific Misconduct There will be an Institutional policy to describe how allegations of scientific misconduct are treated Inquiry phase fact finding to determine that there is allegation of misconduct - proceed to investigation Investigatory phase in-depth examination of situation involving meeting with involved parties Outcome of investigation if proven, sanctions imposed by institution

22 Conflict of Interest Financial interests and arrangements of clinical investigators that could affect the reliability of data to be submitted to the FDA should be identified. An applicant is required to submit to FDA a list of clinical investigators who conducted covered clinical studies and certify and/or disclose certain financial arrangements as follows: 1. Certification that no financial arrangements with an investigator have been made where study outcome could affect compensation that the investigator has no proprietary interest in the tested product

23 CON T that the investigator does not have a significant equity interest in the sponsor of the covered study and that the investigator has not received significant payments of other sorts (cumulative monetary value of $25,000) &/or 2. Disclosure of specified financial arrangements and any steps taken to minimize the potential for bias

24 Case of Scientific Misconduct Andrew Wakefield, a British surgeon and researcher, who is best known for his work regarding the MMR vaccine and its claimed connection with autism and inflammatory bowel disease He was the lead author of a 1998 study, published in The Lancet, which reported bowel symptoms in twelve children diagnosed with autism spectrum disorders, to which the authors suggested a possible link with the MMR vaccine The paper, press conference and resulting media coverage were linked to a steep decline in vaccination rates in the United Kingdom and a sharp rise in confirmed cases of measles, with two child fatalities, as well as others seriously ill on ventilators

25 CON T Subsequent investigation failed to confirm or reproduce Wakefield's findings. The interpretation section of the 1998 paper was subsequently retracted by ten of the paper's thirteen authors In 2004, an investigation revealed unreported conflicts of interest; and an allegation of scientific misconduct was claimed against Wakefield In March 2004, the British General Medical Council (GMC) announced an inquiry into Deer's allegations of misconduct against Wakefield and two former colleagues In 2009 alleged scientific misconduct by Wakefield in that he "fixed" the results of the Lancet paper The panel ruled that Wakefield had "failed in his duties as a responsible consultant", acted against the interests of his patients, and acted "dishonestly and irresponsibly" in his controversial research

26 CON T On February 2, 2010, The Lancet retracted his 1998 publication, noting elements of the manuscript had been falsified. Wakefield does not have a medical license in the United States, and was struck off the United Kingdom medical register in May 2010.

27 Consequences of Unethical Research Conduct Inability to present/publish data when investigators are required to provide evidence of IRB approval Inability of student to use data collected without IRB approval in thesis/dissertation Inability to use data generated by unapproved research in external or internal grant proposals (particularly to federal agencies or other sponsors that adhere to requirements for protections of human subjects)

28 CON T Harm done to institutional reputation if the absence of required oversight by IRB becomes publicly known, and the loss of trust in the institution s commitment for ethical treatment of human subjects Most harmfully, the message of the intentional disregard of institutional requirements that is being sent to student and other members of research team about the ethical integrity of investigator

29 Thank you