Ethical challenges in research during an epidemic outbreak Krittaecho Siripassorn, MD Chair of the IRB of BIDI Bamrasnaradura Infectious Diseases Institute Nov 2015

Background In an outbreak situation public health authorities undertake a rapid response to document existence and magnitude of epidemic and to implement appropriate measures timeliness is major requirement, for research during outbreak –thus the approval from IRB is an ethical challenges in this situation

Challenges in reviewing research in disease outbreak –Timeliness of IRB reviewing procedure –Appropriateness of alternative mechanism of IRB reviewing procedure –Protection rights and welfare of individuals –Outbreak investigation/research activities should be in a timely manner to control the disease Background How to comply with ethical requirement that research be approved by IRB and still enable prompt response when outbreak occurs

Research VS Public Health Practice during outbreak Research Public Health Practice Research Public Health Practice

Research VS Public Health Practice during outbreak ResearchPublic Health Practice  population surveillance, disease control and prevention, and program development & evaluation  collection information or human biological specimens without ICF  subject to public health laws and regulations, do not typically undergo prospective ethics review  Primary intent: “prevent or control disease or injury and improve health, or to improve a public health program or service”

Research VS Public Health Practice during outbreak Research Public Health Practice human biological specimens without ICF Data & infromation Retrospcetive study of these data might be difficult to approved in some case of non- compliance and substandard ethics conduct  Study with Anonymous samples without personal health information --> difficult to generate valuable knowledge  going back to get consent from sampled individuals, which could be logistically difficult, and almost impossible

Momattim H. Int J Infect Dis Booth CM. JAMA 2003 Leong HN. Trop Med Int Health.2004 Example of research product from Public Health Practice Ribavarin for Px patients infected with SARS

Research VS Public Health Practice during outbreak Research Public Health Practice  require prospective independent review IRB, unless they meet certain criteria for exemption  Primary intent: “generate or contribute to generalizable knowledge”

Research VS Public Health Practice during outbreak Public Health Practice Research Epidemiologic research Clinical trial

Research during outbreak (1) Epidemiologic research Clinical trial  well-established procedure for ethics review should apply to all research conducted in a disease outbreak  Generally, it’s procedure are likely to be blood drawing and survey completion  Vulnerable subjects are generally involved and need for additional safeguard

Research during outbreak (2) Macklin R, PLoS Negl Trop Dis Epidemiologic research Clinical trial  Committees could establish a procedure for disease outbreak investigations esp. epidemiologic study  A full, detailed protocol might not be submitted.  A shorter document should be acceptable describing: 1.Background 2.Objective 3.study procedure 4.informed consent procedures 5.steps to protect the confidentiality of information obtained from the individuals

Research during outbreak (3) Macklin R, PLoS Negl Trop Dis Epidemiologic research Clinical trial ICF documents of the research during outbreak  Main content should explain 1.That what they are consenting to is research, and not routine activities carried out by public health practitioners during a disease outbreak 2.Whether identifiable information is collected and how it is collected It is surely not necessary to include all 26 items listed as “essential information for prospective research subjects” in the CIOMS International Ethical Guidelines for Biomedical Research

There was an announcement of one MERS patient in Thailand on June 2015 The case and close contacts were finally transferred to our institute (BIDI) for quarantine  Caused by Corona virus  human to human transmission with unknown mechanism  occurred in health care facilities in several countries

Serology of healthcare workers who exposed to a patient with MERS To evaluate effectiveness of infection controlled procedure of MERS-CoV in health care workers who contact the MERS patient by measuring antibody level to the MERS-CoV Inclusion: –Healthcare worker who take care the MERS patient or Laboratory workers who involves with biological sample Study procedure: –Two blood samplings from each subject (within 14 days from exposure for the first blood sampling) Wiboonchutikul S, with permission

IRB reviewing procedure Draft a concept proposal Writing full protocol on Jul 7, 2015 Protocol submission on Jul 8, 2015 Protocol revision submitted on Jul 9, 2015 Protocol Approval on Jul 9, 2015 Experienced IRB members helped the PI to develop the full protocol Contact to all IRB members to have an Emergency meeting on Jul 9, 2015 Emergency meeting: Jul 9, 2015 Minor revision Primary reviewer reviewed and approved the corrections

Research during outbreak (2) Epidemiologic research Clinical trial Repeated occurrence of outbreak, eg chloera Outbreak with novel disease-causing agents, eg. SARS, MerCoV

Clinical trial/research during outbreak Macklin R, PLoS Negl Trop Dis Repeated occurrence of outbreak, eg chloera Outbreak with novel disease-causing agents, eg. SARS, MerCoV  exact time of outbreak is unpredictable  Outbreak area is predictable  investigators can prepare a “model protocol,” for full review to the IRB 1.Omitting items that are specific to the time and place of the predicted outbreak 2.When the outbreak occurs, investigators can complete the specific information for review by the committee

Clinical trial/research during outbreak Macklin R, PLoS Negl Trop Dis Repeated occurrence of outbreak, eg chloera Outbreak with novel disease-causing agents, eg. SARS, MerCoV  exact time of outbreak is unpredictable  Outbreak area is predictable  investigators can prepare a “model protocol,” for full review to the IRB 1.Omitting items that are specific to the time and place of the predicted outbreak 2.When the outbreak occurs, investigators can complete the specific information for review by the committee

Clinical trial/research during outbreak Macklin R, PLoS Negl Trop Dis Repeated occurrence of outbreak Outbreak with novel disease-causing agents, eg. SARS, MerCoV  difficult to study  epidemic was both rapid in its onset  causative agent is initially unknown  no existing approved treatment protocols are in place

 Evidences of guideline of treatment for MERS generally based on studies on SARS  Retrospective studies (n = 6)  Prospective cohort studies (n = 3)  Randomized clinical trials (n = 4)

Emergency research ≠ outbreak Emergency use exemption criteria: –(1) a life threatening situation and no standard treatment is acceptable –(2) insufficient time to convene a quorum for FB IRB approval This rule can not generally apply for research or trial during an outbreak

Take home message ethical review and approval are needed for an investigation of a disease outbreak Timeliness of IRB procedure is a major challenge for research during outbreak –Can be improved by a various mechanism such as model protocol, establishing an IRB reviewing procedure for disease outbreak research