A Manual for Participants in Clinical Trials of Investigational Agents ...

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5.6 How to Obtain Information about Phase 2 Agents 5.6.1 Investigator’s Brochure This document contains all relevant information about the agent, including animal screening, preclinical toxicology, detailed pharmaceutical data, pharmacology and mechanism of action. The brochure also contains information about the clinical adverse events observed in clinical trials. CTEP has an Investigator’s Brochure for each investigational agent it sponsors. CTEP provides these routinely to investigators who are approved to conduct a clinical trial of the agent at the time the LOI is approved, and when the Investigator’s Brochure is updated. When necessary, investigators with approved LOIs or protocols may obtain the Investigator’s Brochure from the Pharmaceutical Management Branch (ibcoordinator@mail.nih.gov). 5.6.2 IDB Physicians CTEP assigns each DCTD investigational agent to an IDB staff physician, who is responsible for coordinating the agent’s clinical development. When an investigator has important concerns about the design of a contemplated trial, he or she should contact that physician. 5.6.3 Clinical Research Pharmacists The Pharmaceutical Management Branch has a staff of clinical research pharmacists who interact closely with IDB and Clinical Investigations Branch (CIB) staff physicians. Clinical research pharmacists are available to provide pharmaceutical and agent information data on DCTD investigational agents. (See Appendix IV for contact information). Section 5 - Investigator’s Manual 2009 24
6 Phase 3 Trials 6.1 Scientific Policies of CTEP If investigators observe a study agent’s significant activity in any disease during phase 2, further clinical trials usually compare the experimental therapy’s efficacy with that of a standard or control therapy. If reasonable standard treatment can be defined for the disease in question, we generally wish to know whether the new agent or therapy constitutes a significant contribution in terms of patient benefit. A variety of trial designs may be suitable, according to the state of the art treatment in the particular disease. Those that are most satisfactory are controlled trials that compare the new agent to a standard single agent or a standard regimen plus the experimental agent to the standard regimen alone. Regardless of the design selected, however, an appropriate control group must exist and relevant endpoints must be used to measure relative effects. Of greatest medical importance are relative survival and quality of life. Other measures, such as complete remission rate or disease-free survival, may also be of interest. These studies, which attempt to isolate a new agent’s role in the treatment of a specific cancer, are of obvious importance to pharmaceutical collaborators because the results are pivotal in applications to register the agent for commercial distribution. They are of equal importance to the oncology community, because such approval makes the agent generally available for patient care. These trials’ results may also be of great medical importance. If the control group is properly selected such trials may yield valuable information for the care of cancer patients. Every protocol must contain a section that discusses the study design and the plan for data analysis. The investigator should state the study’s major objectives as hypotheses to be tested, and a target sample size should be clearly specified. They should justify the sample size goal in terms of precision of estimation or of levels of type I and type II error. In a phase 3 study, it is insufficient simply to give the number of patients to be accrued on each arm. The protocol should specify the test to be used to compare the treatment groups, and the probabilities of drawing incorrect conclusions when performing this test with the proposed sample size should be given. The magnitude of improvement in outcome that can be reliably detected using the planned sample size should also be specified. The accrual rate of eligible patients per year that can be realistically anticipated should be stated and documented. The protocol should describe specific statistical plans for interim analysis of accumulating data. Phase 3 randomized trials supported by NCI are required to have a Data Monitoring Committee (Data and Safety Monitoring Board) with organization, responsibilities and operations consistent with NCI policy (http://deainfo.nci.nih.gov/grantspolicies/datasafety.htm) and CTEP policy (http://ctep.cancer.gov/branches/ctmb/clinicalTrials/monitoring_coop_ccop_ctsu.htm) for therapeutic trials conducted by the cooperative groups. The plan for the Data Monitoring Committee to monitor interim results should be indicated in the protocol. If evaluation of treatment effect will require use of nonrandomized controls, a thorough description of the control group to be employed should be part of the protocol. This description should include a detailed discussion of comparability issues and analytic techniques. 6.2 Who Is Eligible to Conduct Phase 3 Trials Section 6 - Investigator’s Manual 2009 25
Page 1 and 2: A Manual for Clinical Investigators
Page 3 and 4: 7.1.3 Purpose .....................
Page 5 and 6: 13.4 Responsibilities of Clinical S
Page 7 and 8: 1 Introduction This manual explains
Page 9 and 10: drugs and biologics rests with the
Page 11 and 12: costs might include additional labo
Page 13 and 14: 3 The Clinical Trial Site and the I
Page 15 and 16: CTEP's site visit monitoring progra
Page 17 and 18: 4 Phase 1 Trials The Development of
Page 19 and 20: Because the correlation between sch
Page 21 and 22: for organ dysfunction studies. The
Page 23 and 24: efore writing a formal LOI. IDB sta
Page 25 and 26: CTEP has based its guidelines conce
Page 27 and 28: 5.1.4 Randomized Phase 2 Studies A
Page 29: • Physician members of CCOPs for
Page 33 and 34: completed by the Cooperative Group
Page 35 and 36: clinical trial participation to all
Page 37 and 38: proposer that the submission will n
Page 39 and 40: at the FDA, and for the listing of
Page 41 and 42: expected adverse events that the pa
Page 43 and 44: • How dose modifications will be
Page 45 and 46: consent forms. However, the informe
Page 47 and 48: Investigators’ failure to submit
Page 49 and 50: espond to this re-review in the sam
Page 51 and 52: 9 Ordering Investigational Agents f
Page 53 and 54: the local oncologist(s) must regist
Page 55 and 56: phase 1 include the first time the
Page 57 and 58: investigator send an additional cop
Page 59 and 60: • Altering existing research by m
Page 61 and 62: CTEP has devised a detailed policy
Page 63 and 64: 13 Affiliate Investigators The part
Page 65 and 66: 13.4.3 Cancer Centers The Cancer Ce
Page 67 and 68: 14.3 Administration of Investigatio
Page 69 and 70: • Agents are stored in various pl
Page 71 and 72: 16 Monitoring and Quality Assurance
Page 73 and 74: 16.5 Components of the Quality Assu
Page 75 and 76: Also, please note that medical reco
Page 77 and 78: • Even if the agent has been repo
Page 79 and 80: Appendix I NCI-Cooperative Group-In
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Phase 0 trials do not replace phase
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phase 2 trials enroll 20-30 patient
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the study should be ordered under t
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Appendix IV Key Contact Information
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Appendix V Informed Consent Checkli
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2. Describe risks as outlined in th
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CLINICAL SITE: An institution, coop
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RAB: Regulatory Affairs Branch, htt
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• Agent preparations must be perf
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Procedure for Acute Exposure or Spi
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Appendix VIII National Cancer Insti
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7) Investigational Drug Accountabil
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• Write treatment instructions cl
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• For agent admixtures that can b
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A Manual for Participants in Clinical Trials of Investigational Agents ...

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