1 - 1 An Introduction to Medicine andClinical Research [Seite 12]
1.1 - 1.1 PRECLINICAL RESEARCH [Seite 14]
1.2 - 1.2 CLINICAL RESEARCH [Seite 15]
1.2.1 - 1.2.1 THE FUNDAMENTAL ELEMENTSOF A CLINICAL TRIAL [Seite 16]
1.2.2 - 1.2.2 THE DIFFERENT PARTIES INVOLVED [Seite 19]
1.2.3 - 1.2.3 PHASE I [Seite 21]
1.2.4 - 1.2.4 PHASE II [Seite 22]
1.2.5 - 1.2.5 PHASE III [Seite 23]
1.2.6 - 1.2.6 PHASE IV [Seite 23]
1.2.7 - 1.2.7 REGULATIONS GUIDING CLINICALRESEARCH [Seite 24]
1.2.7.1 - 1.2.7.1 History [Seite 24]
1.2.7.2 - 1.2.7.2 DeclaraQon of Helsinki [Seite 28]
1.2.7.3 - 1.2.7.3 ICH-GCP [Seite 28]
1.2.7.4 - 1.2.7.4 European legislaQon [Seite 30]
1.2.7.5 - 1.2.7.5 Food & Drug AdministraQon [Seite 31]
1.2.7.6 - 1.2.7.6 WHO [Seite 32]
1.2.7.7 - 1.2.7.7 Other regulaQons [Seite 32]
2 - 2 What Makes a GoodMonitor? [Seite 38]
2.1 - 2.1 CHARACTERISTICS [Seite 38]
2.2 - 2.2 RELATIONSHIP WITH THE INVESTIGATOR [Seite 39]
2.3 - 2.3 TOOLS OF A MONITOR [Seite 40]
3 - 3 Key Documents in ClinicalTrials / Documents to Know [Seite 46]
3.1 - 3.1 PROTOCOL [Seite 46]
3.2 - 3.2 INFORMED CONSENT FORM [Seite 48]
3.3 - 3.3 CRF [Seite 50]
3.4 - 3.4 INVESTIGATOR BROCHURE [Seite 52]
3.5 - 3.5 SOURCE DOCUMENTS [Seite 53]
4 - 4 Investigator Selection [Seite 56]
4.1 - 4.1 SOURCES [Seite 57]
4.2 - 4.2 COLD CALL [Seite 57]
4.3 - 4.3 CONFIDENTIALITY [Seite 58]
5 - 5 How to Prepare a Visit [Seite 62]
6 - 6 Pre-Study Visit [Seite 66]
6.1 - 6.1 WHAT TO CHECK [Seite 66]
6.2 - 6.2 HOW TO CHECK [Seite 68]
6.3 - 6.3 PROTOCOL READINESS [Seite 68]
6.4 - 6.4 WHAT TO DO AFTER A VISIT [Seite 69]
6.4.1 - 6.4.1 FOLLOW-UP LETTER [Seite 69]
6.4.2 - 6.4.2 DOCUMENTATION [Seite 69]
7 - 7 The Initiation Visit [Seite 76]
7.1 - 7.1 TRAINING [Seite 76]
7.2 - 7.2 HOW TO ... [Seite 77]
7.3 - 7.3 WHAT TO DO AFTER AN INITIATION VISIT [Seite 78]
7.3.1 - 7.3.1 FOLLOW-UP LETTER [Seite 78]
7.3.2 - 7.3.2 DOCUMENTATION [Seite 79]
8 - 8 Monitoring Visits [Seite 84]
8.1 - 8.1 SOURCE DATA VERIFICATION [Seite 85]
8.1.1 - 8.1.1 ELECTRONIC CRF [Seite 86]
8.1.2 - 8.1.2 PAPER CRF [Seite 86]
8.2 - 8.2 INVESTIGATIONAL MEDICINAL PRODUCT [Seite 87]
8.2.1 - 8.2.1 DEFINITIONS [Seite 87]
8.2.1.1 - 8.2.1.1 Inves7ga7onal medicinal product [Seite 87]
8.2.1.2 - 8.2.1.2 Medical device [Seite 87]
8.2.1.3 - 8.2.1.3 Accessory [Seite 88]
8.2.1.4 - 8.2.1.4 AcYve implantable medical device [Seite 88]
8.2.1.5 - 8.2.1.5 In vitro diagnosYc devices (IVD): [Seite 88]
8.2.2 - 8.2.2 IMPORT AND EXPORT [Seite 88]
8.2.3 - 8.2.3 IMP DISTRIBUTION [Seite 89]
8.2.4 - 8.2.4 TRACKING OF IMP: SHIPMENTS [Seite 90]
8.2.5 - 8.2.5 RETURN OF USED/UNUSED IMP [Seite 91]
8.2.6 - 8.2.6 TRANSFER [Seite 91]
8.2.7 - 8.2.7 CERTIFICATE OF ANALYSIS [Seite 91]
8.2.8 - 8.2.8 INVESTIGATIONAL PRODUCT [Seite 91]
8.2.9 - 8.2.9 LABELING [Seite 92]
8.2.10 - 8.2.10 SITE INVENTORY &PATIENT ACCOUNTABILITY FORM [Seite 92]
8.2.11 - 8.2.11 STORAGE CONDITIONS [Seite 93]
8.2.12 - 8.2.12 IMP DESTRUCTION [Seite 94]
8.3 - 8.3 FILING [Seite 94]
8.4 - 8.4 SITE MANAGEMENT [Seite 95]
8.5 - 8.5 RECRUITMENT ISSUES [Seite 96]
8.5.1 - 8.5.1 THE RIGHT PROTOCOL [Seite 96]
8.5.2 - 8.5.2 SELECTION AND SUPPORT OF STUDY SITES [Seite 96]
8.5.3 - 8.5.3 HOW TO HELP SITES? [Seite 99]
8.5.4 - 8.5.4 KEEPING TRACK [Seite 100]
8.6 - 8.6 SAFETY [Seite 102]
8.6.1 - 8.6.1 ADVERSE EVENT (AE) [Seite 102]
8.6.2 - 8.6.2 ADVERSE DRUG REACTION (ADR) [Seite 104]
8.6.3 - 8.6.3 SERIOUS ADVERSE EVENT (SAE) [Seite 105]
8.6.4 - 8.6.4 SUSPECTED UNEXPECTED SERIOUSADVERSE REACTION (SUSAR) [Seite 106]
8.6.5 - 8.6.5 NOTIFICATION TO EC AND THEAUTHORITIES (EUROPEAN LEGISLATION) [Seite 107]
8.7 - 8.7 REPORTING BY THE MONITORS [Seite 108]
8.8 - 8.8 WHAT TO DO AFTER A MONITORING VISIT [Seite 109]
8.8.1 - 8.8.1 FOLLOW-UP LETTER [Seite 109]
9 - 9 The Close-Out Visit [Seite 114]
9.1 - 9.1 WHAT TO DO AFTER A CLOSE-OUT VISIT [Seite 115]
9.1.1 - 9.1.1 FOLLOW-UP LETTER [Seite 115]
9.1.2 - 9.1.2 DOCUMENTATION [Seite 117]
10 - 10 Audits & Inspections [Seite 120]
10.1 - 10.1 HOW TO PREPARE [Seite 121]
10.2 - 10.2 DURING AN AUDIT OR INSPECTION [Seite 121]
10.3 - 10.3 AFTER AN AUDIT [Seite 123]
11 - 11 Reporting & Archiving [Seite 128]
11.1 - 11.1 COMMUNICATION REPORTS [Seite 128]
11.1.1 - 11.1.1 EXTERNAL [Seite 128]
11.1.2 - 11.1.2 INTERNAL [Seite 129]
11.2 - 11.2 SAFETY REPORTING [Seite 129]
11.2.1 - 11.2.1 CIOMS REPORTS [Seite 129]
11.2.2 - 11.2.2 LINE LISTINGS [Seite 129]
11.2.3 - 11.2.3 ANNUAL SAFETY REPORT [Seite 130]
11.2.4 - 11.2.4 CLINICAL STUDY REPORT [Seite 130]
11.3 - 11.3 GOOD DOCUMENTATION [Seite 132]
11.4 - 11.4 ARCHIVING [Seite 133]
12 - Appendix1 Answers to Self Study [Seite 136]
13 - Appendix2 List of Abbreviaions [Seite 140]
14 - Appendix3 Index [Seite 144]
3 Key Documents in Clinical Trials / Documents to Know
In this chapter you will learn:
What informaKon is crucial to know?
Where can I find this informaKon?
What are good study documents?
3.1 PROTOCOL
According to ICH-GCP 1.44 a protocol is: "A document that describes the objecnve(s), design, methodology, stansncal consideranons, and organizan- on of a trial. The protocol usually also gives the background and ranonale for the trial, but these could be provided in other protocol referenced documents." For a clinical monitor the protocol is his basic manual. In the protocol the clinical study is explained in detail in several secnons. These secnons are quite standardized from protocol to protocol, since they are outlined by the Internanonal Conference of Harmonizanon. In general the following secnons are used: General Informanon, Background Informanon, Trial Objecnves and Purpose, Trial Design, Selecnon and Withdrawal of Subjects, Treatment of Subjects, Assessment of Efficacy, Assessment of Safety, Stansncs, Direct Access to Source Data/Documents, Quality Control and Quality Assurance, Ethics, Data Handling and Record Keeping, Financing and Insurance, Publicanon Policy, Supplements (annexes).
You have to read and understand the protocol thoroughly, as you will have discussions with the invesngator later on. Furthermore, youwill need to train or oversee the training of the site personnel on the study treatments, so during the ininanon phase of the trial youwill need to be an expert on the protocol. Of course your company also has the obliganon (ICH-GCP secnon 5.18.2) to train you on the protocol and especially on the indicanon, the conduct of the trial and the relevant stansncal consideranons.
