International Research Basic Topics to Consider. International Subcommittee Regulatory Foundations, Ethics and Law Program

Transcription

1 International Research Basic Topics to Consider International Subcommittee Regulatory Foundations, Ethics and Law Program

2 Presentation Outline Study Planning, Implementation, and Monitoring Considerations for planning an international research study involving human subjects Obtaining assurance for international sites Identifying whether countries that have different expectations or rules FDA international guidelines Considerations for sending/receiving data or samples Obtaining non-us insurance to cover SAEs that occur at an international site Monitoring international study conduct 2

3 Considerations for Planning an International Research Study Involving Human Subjects Ethical and Cultural Issues Ethics Assess the norms/expectations, communicate those back to your IRB Cultural considerations: Avoid faux pas Be aware of business attire, meeting formats, local languages, and cultural norms Emphasize collaboration, set expectations, but keep an open mind 3

4 Considerations for Planning an International Research Study Involving Human Subjects Site Selection Determine appropriate affiliation Assess current infrastructure Travel, safety, and security PI Selection Clinical and research experience Seniority within institution Community relationships Institutional training 4

5 Considerations for Planning an International Research Study Involving Human Subjects Regulatory Issues Ascertain local laws and customs, and consider: Import/export issues HIPAA Data security Procurement laws and policies Credentialing IP rights/copyright concerns 5

6 Considerations for Planning an International Research Study Involving Human Subjects Budgeting for Research: Sponsors and institutional requirements Know what can be budgeted in terms of directs, indirects, $ for human subjects: Indirects as directs Participant stipends: how much? Fuel/transport: sometimes you can t just show up Ideal input from local PI or project coordinator Negotiation with the local grants office Currency fluctuations 6

7 Considerations for Planning an International Research Study Involving Human Subjects Make sure ALL collaborators are on the same page regarding: Cultural expectations Scope of work Financial reporting Audit Human resources/personnel 7

8 Obtaining Assurance for International Sites The Federalwide Assurance (FWA) is an assurance of compliance with the U.S. federal regulations for the protection of human subjects in research. FWAs are approved by the Office for Human Research Protections (OHRP) for all human subjects research conducted or supported by the U.S. Department of Health and Human Services (HHS). An institution applying for a FWA will need to designate an IRB that has been registered with OHRP. If the international site has an IRB that will be reviewing the research, that IRB should register with OHRP prior to submitting the FWA application. Assurances must be renewed every five years; IRB registrations must be renewed every three years. Changes to the FWA and/or the IRB registration must be submitted within 90 days of the change. Source: h7p:// 8

9 Identifying whether countries have different expectations or rules Different Regulations/Guidelines Many countries implement different regulations than those issued by DHHS (45 CFR 46) DHHS regulations are not always sufficient for ethical review in other countries Thoroughly research the rules of the setting in which you wish to work Identify applicable ethical guidance, e.g., Declaration of Helsinki, CIOMS, etc. Familiarize yourself with host countries requirements Consider host countries expectations/rules/requirements to ensure a strong working relationship between US-based and local research staff 9

10 Identifying whether countries have different expectations or rules Defer to the expertise of your in-country colleagues Knowledge of local culture and customs provided to you by your collaborators is crucial. Local colleagues can inform you of potential site-specific regulations, provide input on the local ethical review process, and offer guidance on establishing CABs if required. Working with the local ethical review committee on protocol development may prevent delay in approval at the host-country level. 10

11 Identifying if Countries have Different Expectations or Rules Establish a working relationship with local ethical review committee If amenable, local reviewers may provide you with information about relevant local requirements during the protocol development process If a local ethical review committee requires that US researchers provide efforts to build capacity, then US-based researchers should consider implementing appropriate capacity-building efforts 11

12 FDA International Guidelines Items to consider for FDA trials: Check with your US-based institution regarding IND/IDE submissions FDA international guidelines: There may be country-specific regulations for drug and device development For local/regional international regulatory agencies: For local/regional international clinical regulations: 12

13 FDA International Guidelines Other items to consider: Is this a study to assess a drug/device for the US and/or international market? Are you adding an international site to increase enrollment for US approval? Is the population unique or vulnerable? Harvard Catalyst guidance on IND/IDE: h7p://catalyst.harvard.edu/programs/regulatory/indide.html 13

14 Considerations for Sending/Receiving Data or Samples Regulatory guidelines for sending/receiving data or samples can be found at: Some regulatory considerations: Are the samples/data coded? If yes, who has access to the code? Where is the master kept and who has access to this master file? Some countries may require separate approvals or consent for storing, sending, or receiving specimens or data. 14

15 Considerations for Sending/Receiving Data or Samples Data Transfer Check local law, requirements Check your institutional data security policy Guidance is provided for research involving coded or private information by OHRP at Some practical considerations for collecting electronic data on site include: Availability of WiFi and/or internet connections Size/type of data set Availability of a secured data line Establishment of a process for handling data breaches 15

16 Considerations for Sending/Receiving Data or Samples Biological Samples Are the samples being processed on-site or shipped to another location? Check with your shipping department for your institutional guidelines on international shipping of biological samples. BUDGET shipping costs are high especially if there are special conditions i.e. dry ice, remote locations Identify a customs clearance agent on the receiving end. Customs clearance agents are also used to facilitate receipt of the shipment. These agents are unique to each country and have the expertise and knowledge of local customs regulations and laws. 16

17 Considerations for Sending/Receiving Data or Samples Biological Samples Use of a global shipping company to facilitate customs navigation on both ends. Some important questions to ask. Do they: Provide global coverage Have Insurance Have validated packaging and temperature monitoring (including frozen, refrigerated, and ambient) Provide monitoring of consignment clearance and assistance with all customs queries Have experience of dealing with customs and regulatory bodies Have permits identified and obtained for shipping of sensitive or regulated material 17

18 Adverse Events and International Sites Research that presents more than minimal risk: Participants must be made aware of any medical treatments or compensation available for research-related injuries, including the issue of who will pay for the treatment. There is no US federal requirement for treating or compensating participants for research-related injuries. Projects, grants, and contracts that involve potential medical risks: Include how those risks will be minimized or managed (clinically and operationally) and identify who pays for any incurred expenses. If the project is industry sponsored, contracts/clinical trial agreements should address payments for research-related injuries, both short- and long-term. Be aware of medical and insurance standards in the countries where you are conducting research. This is a country-specific issue; your general counsel and IRB (local and international site) are your best sources of guidance. 18

19 Adverse Events and International Sites Consent materials: Outline real and potential risks. Include an In case of injury statement that specifies what will occur in the case of an adverse medical event or an unanticipated problem; these statements should be reviewed and approved by the IRB and by institutional general counsel. Statements should indicate whether treatment and/or compensation is available for research-related injuries. Do not promise more care/treatment than can be delivered. 19

20 Monitoring International Study Conduct 1. Pre-study Initiation visit Demonstrates PI/study team preparedness Starts the study on the right foot 2. Periodic visit Evaluates compliance throughout the course of the study Identifies and corrects noncompliance 3. Participant file review Consider sample vs. 100% review 4. Monitoring reports 20

21 Monitoring from Afar 1. Interactive video and audio chat Skype Facetime Google chat 2. Secure file sharing options 3. Education training/webinar platforms WebEx Go To Meeting 21

22 Your Feedback Matters We are committed to providing information that is openly accessible to investigators, institutions, and community partners for education and training purposes. We are interested in constantly improving and updating our materials. If you have any suggestions about this material, please contact us at: Your feedback matters. For additional information about International Research and the International Subcommittee visit: h7p://catalyst.harvard.edu/programs/regulatory/internahonalresearch.html 22

23 About the International Subcommittee The International Subcommittee brings together expertise from Harvard Catalyst s participating institutions to address regulatory issues in international research, foster collaboration, and reduce barriers for investigators and IRBs. The charge of the subcommittee is to develop tools, training materials, and education to help IRBs and investigators Build global health community connections for investigators and IRBs Meet regulatory requirements Navigate regulatory process Ensure research compliance Protect research participants Promote best practice h7p://catalyst.harvard.edu/programs/regulatory/internahonalresearch.html 23

24 International Subcommittee Membership MaryAnn Cugini The Forsyth Institute Peggy Darnowsky MGH Center for Global Health Leslie Howes Harvard Longwood Medical Area IRB Paul Hryvniak Harvard Longwood Medical Area IRB Pamela Richmond Hebrew SeniorLife Rachel Rifkin MGH Center for Global Health Alyssa Speier Harvard Longwood Medical Area IRB h7p://catalyst.harvard.edu/programs/regulatory/internahonalresearch.html 24

25 Citing These Slides We encourage you to reproduce and use these materials freely. In doing so, we require that you acknowledge Harvard Catalyst as the publisher and give appropriate credit to the individual authors. This material is the work the Harvard Catalyst International Research subcommittee. The International subcommittee is a subcommittee of the Regulatory, Law and Ethics Program, which is affiliated with Harvard Catalyst The Harvard Clinical and Translational Science Center. This work was conducted with support from Harvard Catalyst The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award 8UL1TR and financial contributions from Harvard University and its affiliated academic health care centers). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University, and its affiliated academic health care centers, or the National Institutes of Health. For additional information about citing support: h7p://catalyst.harvard.edu/programs/regulatory/internahonalresearch.html 25