NIS Considerations - Taiwan An overview of the considerations when conducting Non-interventional Studies in Taiwan

Transcription

1 NIS Considerations - Taiwan An overview of the considerations when conducting Non-interventional Studies in Taiwan Stuart McCully Compliance Healthcheck Consulting UK Ltd NIS-C-TW

2 Table of Contents Disclaimer! 8 Regulatory Requirements! 9 COUNTRY-SPECIFIC REGULATORY REQUIREMENTS 9 REGULATORY BODIES 9 DEFINITIONS 10 Human Trial Research 10 Human Research 10 Human Specimens 10 Delinking 10 REGULATORY FRAMEWORK 11 Applicable Legislation & Guidance 11 SUMMARY OF THE NIS REQUIREMENTS IN TAIWAN 13 APPROVAL & NOTIFICATION REQUIREMENTS 14 WHO IS RESPONSIBLE FOR WHAT? 15 REGULATORY SUBMISSIONS ROADMAP 16 REGULATORY SUBMISSIONS DOCUMENTS 17 REGULATORY REQUIREMENTS - USEFUL LINKS 18 Study Conduct Considerations! 21 RESEARCH USING HUMAN SUBJECTS 21 POST-MARKETING SURVEILLANCE STUDIES (PMS) 21 ETHICAL REVIEW 22 1

3 IRB Review 22 List of Taiwan IRBs 22 IRB Penalties 24 IRB Review Challenges 25 Expedited IRB Review 25 IRB Conflicts of Interest 25 The Joint Institutional Review Board (JIRB) 26 JIRB Application Process for Post-Marketing Surveillance Studies (PMS) 27 JIRB Application Form 29 CONTRACTS 34 CONSENT 35 Consent Requirements 35 Informed Consent for Post-Marketing Surveillance Studies 35 Consent Process 36 Adults 37 Minors 37 Penalties for Non-Compliance 37 ABORIGINES 37 STUDY SITES 38 Site Authorisation 38 Investigator Training Requirements 38 LOCAL REPRESENTATION 38 Special Requirements for CROs 39 MATERIAL ACQUIRED DURING RESEARCH 39 ANNUAL REPORTS 40 JIRB Annual Report Submission Process 40 JIRB Annual Report Form 41 SAFETY REPORTING 45 2

4 Post-Marketing Surveillance 45 Marketed Medicinal Products 45 Definition - Serious Adverse Drug Reaction 45 Management of Reporting 46 For Fatal or Life-threatening Serious Adverse Reactions 46 For All Other Serious Adverse Reactions 47 For Non-Serious Adverse Reactions 47 How to Report 47 Newly Marketed Medical Products 47 Definition - New Drug 48 Schedule of Reporting PSUR 48 Content in the Periodic Safety Update Report (PSUR) 48 Final Summary Bridging Report 49 How to Report 49 PROTOCOL AMENDMENTS 51 JIRB Protocol Amendment Form A - Signed by Each PI 52 JIRB Protocol Amendment Form B - Signed by the Chief Investigator on Behalf of the PIs 55 END OF STUDY NOTIFICATION 59 IRB Closure Report 59 STUDY CONDUCT CONSIDERATIONS - USEFUL LINKS 63 Data Privacy Considerations! 65 DEFINITIONS 65 Personal Information 65 Personal Information File 65 Collection 65 Processing 66 Use 66 3

5 International Transmission 66 Government Agency 66 Non-Government Agency 66 The Party 66 COLLECTION OF PERSONAL INFORMATION 67 CONSENT 67 Consent Obligations 67 Content of Consent 67 RIGHTS OF THE INFORMATION DONOR 68 SECURITY OF PERSONAL INFORMATION FILES 68 DAMAGES AND CLASS LITIGATION 69 Liability for Illegal Collection, processing and Use of Personal Information 69 The Right to Claim for Damage Compensation 69 DATA PRIVACY CONSIDERATIONS - USEFUL LINKS 70 Human Tissue Research! 71 DEFINITIONS 71 Specimen(s) 71 Specimen Donor 71 Specimen User 71 Specimen Custodian 72 ID Encoding 72 De-linking 72 Remnant Specimen(s) 72 COLLECTION AND USE OF HUMAN SPECIMENS FOR RESEARCH 72 Ethics Approval 73 Informed Consent Requirements 73 Collection of Specimens from an Embryo or Fetus 74 4

6 Notification of Commercial Interests 75 Notification of Results that have a Significant Impact on the Personal Health of a Donor 76 Specimen to be Used within the Constraints of the Donor Consent 76 Refusal or Withdrawal of Consent 76 Management of Specimens 77 Storage and/or Destruction of Specimens on Completion of Studies 77 Data Privacy 77 Transfer of Specimens to Foreign Countries 78 Consent Waiver 78 RE-USE OF MATERIAL ACQUIRED DURING RESEARCH 78 JIRB APPLICATION PROCESS FOR GENETIC RESEARCH STUDIES 80 HUMAN TISSUE RESEARCH CONSIDERATIONS - USEFUL LINKS 82 Best Practice Considerations! 83 CLINICAL RESEARCH 83 Transparency 83 Distinct from Promotion 83 Post-Marketing Surveillance Studies (PMS) 84 Mandatory Medical Components for Post-Marketing Studies 84 Essential Components for Post-Marketing Studies 85 Format for PMS Registry System 86 Further PMS Considerations 86 What is the definition of a PMS? 86 What are the scopes of the post marketing studies that should be posted on IRPMA the website? 87 Following the approval by the IRB, JIRB, when should the PMS be posted on IRPMA website? 87 Are all items in the template for PMS registry system necessary? (The Objective, No. of Sites, No. of Patients) 87 5

7 ENGAGING HEALTHCARE PROFESSIONALS AS CONSULTANTS 88 GIFTS 88 Prohibition of Cash & Personal Gifts 88 Promotional Aids 89 What can be given as a promotional aid? 89 How to justify the promotional aids in Article 7.5.2? Are electronic goods (such as a USB flash disk) included in the scope of personal gifts as stated in Article 7.5.1? 89 Items of Medical Utility 90 What kinds of items are envisaged as being items of medical utility? 90 Are lucky draws allowed? 90 Cultural Courtesy Gifts 90 EVENTS 91 Scientific and Educational Objectives 91 Is there any restriction for accommodation, number of participants, or ceiling when sponsor a symposium, congress or other medical health care or educational program? 91 Events Involving Foreign Travel 91 When is it appropriate and justified for a company to organize or sponsor an event for healthcare professionals outside of their home country? 91 Promotional Information at Events 92 Appropriate Venue 93 In case of one-day program, if participants who have difficulties to return to their home town on that day due to traffic problem, what shall we do? 93 Limits of Hospitality 94 Hospitality should be limited to refreshments and/or meals incidental to the main purpose of the Event. What is the definition of the Event? 94 Sponsorship 94 Is there any consideration for sponsoring HCPs attending overseas event? 95 In regard to flight tickets under sponsorship, in case that there is no business class but only economy and first class available, what shall the company do? 95 Guests 96 6

8 While attending an event, are the invitees allowed to bring guests? 96 Events - Further Considerations 96 HCP Payment for Service 96 Is it necessary to have a contract with the invited healthcare professional as speakers or presenters for the payment of honorarium and related travelling and boarding expenses? 97 For the honorarium for local speaker to lecture overseas or to lecture in international symposia in Taiwan, should the international norms or a limit of up to NT$5,000/hr be applied? 97 How to calculate additional payment? 97 ENTERTAINMENT 98 The IRPMA Code prohibits companies from providing entertainment, leisure and social activities to healthcare professionals and other stakeholders. Are there exceptions to this rule? 98 Are individual social activities with healthcare professionals such as golf, music concert, etc. allowed? 98 BEST PRACTICE CONSIDERATIONS - USEFUL LINKS 100 NIS Definitions! 101 EUROPEAN NIS DEFINITIONS 101 NIS DEFINITIONS 101 Non-interventional Study (NIS) 101 Post-authorisation Safety Study (PASS) 102 Post-authorisation Efficacy Studies (PAES) 102 Common NIS Terminology! 103 COMMONLY USED NIS TERMS 103 COMMON NIS TERMINOLOGY 103 7

9 Disclaimer Although this Compilation contains information of a legal nature, it has been developed for informational purposes only and does not constitute legal advice or opinions as to the current operative laws, regulations, or guidelines of any jurisdiction. In addition, because new standards are issued on a continuing basis, this Compilation is not an exhaustive source of all current applicable laws, regulations, and guidelines relating to non-interventional studies. While reasonable efforts have been made to assure the accuracy and completeness of the information provided, researchers and other individuals should check with local authorities and/or research ethics committees before starting research activities. 8

10 Regulatory Requirements COUNTRY-SPECIFIC REGULATORY REQUIREMENTS REGULATORY BODIES Competent Authority Research Ethics Committees Data Protection Agency Pharmaceutical Self-Regulation Body Pharmaceutical Code of Practice Taiwan Food and Drug Administration (TFDA)* Joint Institution Review Board (JIRB) Not Applicable** International Research-Based Pharmaceutical Manufacturers Association (IRPMA) IRPMA Code of Practice 2012^ * The regulatory system for the safety and quality of food, drug, medical device, and cosmetics is critical to the public health. As these products are intimately involved in people s daily life and health as well as medical welfare, the Department of Health had been striving to facilitate organizational reform by focusing on consumer health in terms of food and drug safety. Consolidation of the Bureau of Food Safety, the Bureau of Pharmaceutical Affairs, the Bureau of Food and Drug Analysis and the Bureau of Controlled Drugs into the Taiwan Food and Drug Administration (TFDA) was completed on January 1st, 2010, following the promulgation of the TFDA Organization Act on June 3rd, 2009 (Source - about the FDA). ** The Personal Information Protection Act (PIPA) does not provide for a single oversight body and does not create a data protection agency. Enforcement is left to the Ministries responsible for each industry sector. ^ Effective 1st September 2012, the IRPMA Code of Practice (Updated 2012) replaces the 2007 IRPMA Code of Marketing Practices. Member companies of IRPMA must incorporate this Code into existing internal codes no later than 1st September

11 DEFINITIONS Human Trial Research A human trial research (hereinafter Human Trial shall be conducted prior to the registration of a new drug or medical device or before a medical care institution lists a new medical technology as a regular medical disposition item (as per Article 2 of the Regulations on Human Trials ). Human Research Engaging in research on behavioral ecology, physiology, psychology, genetics, medicine, and the like by obtaining, investigating, analyzing, and applying data related to human specimens or individuals (as per General Provision 4 of the Human Research Act ). Human research shall include all processes seeking to acquire, analyze, and investigate human tissue or information concerning individual behavior, thinking, physiology, psychology, sociology, genetics, and medicine for the purpose of research (as per paragraph 2 of the DoH Human Research Ethics Policy Guidelines ). Human Specimens Human specimens" refers to human organs (including those from fetuses and corpses), tissue, cells, body fluids, or materials derived from test results (as per General Provision 4 of the Human Research Act ). Delinking Whereby once the research material or data has been coded or handled by other means, it will become impossible to link or compare it with any identifiable human research subjects (as per General Provision 4 of the Human Research Act ). 10

12 Study Conduct Considerations CONSIDERATIONS WHEN CONDUCTING NIS IN TAIWAN RESEARCH USING HUMAN SUBJECTS On December 9, 2011, Taiwan's legislature adopted a new law on the use of human subjects in research projects. Previously, research involving humans was governed by the non-binding Ethical Guidelines for Human Research, formulated by the Department of Health in (Taiwan Legislature Greenlights New Human Subject Research Law, TAIWAN TODAY (Dec. 12, 2011).) One key feature of the new law is that it makes informed consent by aborigines a precondition for any research involving them and for release of the research results. (Shih Hsiu-chuan, Legislature Passes Act on Using Human Subjects in Research, TAIPEI TIMES (Dec. 10, 2011).) The purpose of the Act on Human Research Subjects is to better protect the subjects' rights, because those rights "tend to be neglected and thus impinged upon, due to such factors as differential access to information and conflicts of interest between subjects and researchers." (Id.) The Act stipulates that research conducted on humans must respect the subjects' decision-making power, ensure a balance between risks and benefits, minimize infringements, and also attend to the fair assignment of the research burdens and the achievements alike, in order to safeguard the subjects' rights. (Jen-t'i yen-chiu fa [Act on Research Involving Human Subjects] (Dec. 9, 2011) arts. 1 & 2, Parliamentary Library Legislative Yuan website.) (Zeldin, 2011). POST-MARKETING SURVEILLANCE STUDIES (PMS) The objective of PMS study is to collect patient information and to explore the treatment experience in Taiwan. It involved the treatment of indication stated in the approved user guide of drugs. Basing on the Benchmarks of Marketing Practices announced by IRPMA, all the post- marketing drug trials must be approved by the Institutional Review Board, and PMS 21

13 study is no exception. As the drug is already in the market, the treatment is available for the patients. The emphasize of the Institutional Review Board is not to safeguard the safety of the patients going through the treatment, but to protect the privacy of the patients, and whether or not the patients agree to enable the drug manufacturer to access their medical records (as per Attachment 11 of the Human Subject Protection Handbook). ETHICAL REVIEW IRB Review To ensure the protection of human subjects in biomedical research studies, study protocols must be reviewed and approved by an IRB before patient recruitment (as per the JIRB Guidelines). The Human Research Act (2011) requires that a research plan must be approved by an ethics review committee before a research project that involves human subjects can proceed. The committee, to be set up by the research institute concerned, is to comprise a minimum of five disinterested persons of whom at least two-fifths are from outside the institution; neither gender, moreover, may exceed two-thirds of the membership. The Act requires that approved research projects undergo annual reviews. List of Taiwan IRBs The following list is by no means exhaustive and is only provided to aid the reader of this report in their initial IRB due diligence exercises. IRB Human Subject Research Ethics Committee Institutional Review Board, Taipei Veterans General Hospital Website goodexp/content.htm 22

14 PROTOCOL AMENDMENTS Protocol amendments must be approved by the applicable IRB before being implemented. The Joint Institutional Review Board (JIRB) has two amendment forms that are either signed by each individual instigator (Form A) or by the Chief Investigator (CI) on behalf of the Principal Investigators (Form B). Where, proposed protocol amendments are low risk they may be eligible for expedited IRB review. Expedited review requires only approval from the Chairman (or designee), rather than the full IRB committee. (Image Source: IRB of the Taichung Veterans General Hospital) 51

15 Data Privacy Considerations DATA PRIVACY AND DATA PROTECTION CONSIDERATIONS WHEN CONDUCTING NIS IN TAIWAN DEFINITIONS Personal Information The name, date of birth, I.D. Card number, passport number, characteristics, fingerprints, marital status, family, education, occupation, medical record, medical treatment, genetic information, sexual life, health examination, criminal record, contact information, financial conditions, social activities and other information which may be used to identify a natural person, both directly and indirectly (as per Article 2.1 of the Personal Information Protection Act). Personal Information File A collection of personal information built to allow information retrieval and management by automatic or non-automatic measures (as per Article 2.2 of the Personal Information Protection Act). Collection To collect personal information in any form and way (as per Article 2.3 of the Personal Information Protection Act). 65

16 Processing To record, input, store, compile, correct, duplicate, retrieve, delete, output, connect or internally transmit information for the purpose of establishing or using a personal information file (as per Article 2.4 of the Personal Information Protection Act). Use All methods of personal information use other than processing (as per Article 2.5 of the Personal Information Protection Act). International Transmission The cross-border processing or use of personal information (as per Article 2.6 of the Personal Information Protection Act). Government Agency Refers to a government agency or administrative juridical person at the central or local government level which is empowered to exercise sovereign power (as per Article 2.7 of the Personal Information Protection Act). Non-Government Agency Refers to the natural persons, juridical persons or groups other than those stated in the proceeding item (as per Article 2.8 of the Personal Information Protection Act). The Party Means an individual of whom the personal information has been collected, processed or used in accordance with this Law (as per Article 2.9 of the Personal Information Protection Act). 66

17 Human Tissue Research CONSIDERATIONS WHEN CONDUCTING STUDIES WITH HUMAN SAMPLES AND DATA IN TAIWAN DEFINITIONS Specimen(s) Cells, tissue, organs, body fluids or derivatives thereof (containing genetic material) taken from the human body, to include remnant specimens and specimens taken from an embryo, fetus or cadaver (as per Paragraph 2(1) of the DoH Guidelines for Collection and Use of Human Specimens for Research ). Specimen Donor A person from whom a specimen is collected (as per Paragraph 2(2) of the DoH Guidelines for Collection and Use of Human Specimens for Research ). Specimen User A person or institution who/that directly uses the specimen, directs another person to use the specimen or who/that may use the specimen in accordance with a specific relationship, such as a contract, with the specimen provider (as per Paragraph 2(3) of the DoH Guidelines for Collection and Use of Human Specimens for Research ). 71

18 Best Practice Considerations BEST PRACTICE CONSIDERATIONS WHEN CONDUCTING NIS IN TAIWAN CLINICAL RESEARCH Transparency Companies are committed to the transparency of clinical trials which they sponsor. It is recognized that there are important public health benefits associated with making clinical trial information more publicly available to healthcare practitioners, patients, and others. Such disclosure, however, must maintain protections for individual privacy, intellectual property and contract rights, as well as conform to legislation and current national practices in patent law (as per Section 9.1 of the IRPMA Code of Practice, 2012). Companies disclose clinical trial information as set out in the Joint Position on the Disclosure of Clinical Trial Information via Clinical Trial Registries and Databases (2009) and the Joint Position on the Publication of Clinical Trial Results in the Scientific Literature (2010) issued by the IFPMA, the European Federation of Pharmaceutical Industries and Associations (EFPIA), the Japanese Pharmaceutical Manufacturers Association (JPMA) and the Pharmaceutical Research and Manufacturers of America (PhRMA) (as per Section 9.1 of the IRPMA Code of Practice, 2012). Distinct from Promotion All human subject research must have a legitimate scientific purpose. Human subject research, including clinical trials and observational studies, must not be disguised promotion (as per Section 9.2 of the IRPMA Code of Practice, 2012). 83

19 POST-MARKETING SURVEILLANCE STUDIES (PMS) In accordance with Benchmark 9 of the IRPMA Code of Practice, 2012: All PMS shall go through JIRB, IRB or Ethics Committee All human studies including PMS must be approved and managed by Medical Director or equivalent CR Manager of member companies All PMS must be registered on the website of IRPMA PMS registry system IRB approval code or approval date should be shown on study-related documents Mandatory Medical Components for Post-Marketing Studies In accordance with Benchmark 9 of the IRPMA Code of Practice, 2012: Protocol to address scientific objectives To have specific scientific interest Pre-determined sample size justification based on study description Should be based on clinical & statistical significant meaning Patient consent obtained IRB approval secured Follow GCP Guideline Minimum to comply with TW DOH GCP Registry on IRPMA website Payment must be appropriate and according to study design. It must not be set to influence prescribing behavior Must reflect time & efforts from investigators 84