Methodology of Phase I and II trials of anticancer CAM

Summary

Principal Investigator: A Vickers
Abstract: BACKGROUND: Anticancer CAM therapies are increasingly becoming the focus of scientific research. Conventional approaches to early phase trials may not be applicable for the development of some CAM approaches. Perhaps as a result, many CAM therapies taken to clinical trial in cancer have not previously been subject to dose-finding; furthermore, Phase II trials of CAM have often failed to incorporate formal statistical designs. In recent years new designs for Phase I and II trials have been developed in response to the challenges of researching immune, biologic and target-based agents. These methodologies might be usefully adapted for the study of CAM. OBJECTIVES: To review systematically methodologies that have been applied in early phase trials of CAM for cancer; to review systematically available methodologies for such trials; to make specific practical recommendations for future CAM trials based on simulation and analytic studies. METHODS: Three separate systematic reviews will be undertaken of Phase I, II and III trials of CAM in cancer. These will describe previous research and determine the proportion of: Phase I trials that attempted to find an optimal dose; Phase II and III trials that were preceded by dose finding trials; Phase I trials that incorporated a formal statistical design; Phase Ill trials that were preceded by Phase II.A systematic review will be undertaken of Phase I and II designs: each design will be described by pre-specified criteria. The operating characteristics of key Phase I and II designs for CAM will be assessed by simulation and analytic studies. Four sets of dose-response and dose-toxicity functions will be generated for four "archetypal" CAM modalities. Each Phase I design will be tested for each modality: efficiency and closeness of the study dose to a theoretically derived optimal dose will be calculated. Phase II designs will be tested given a range of clinical scenarios common for CAM therapies: sample size and study duration will be compared between designs. The results of these studies will be expressed in non-technical terms so that CAM researchers can make a choice of Phase I and II design depending on simple assumptions about the properties of the modality and cancer population under study.
Funding Period: 2003-06-09 - 2006-05-31
more information: NIH RePORT

Top Publications

  1. pmc Basic introduction to research: how not to do research
    Andrew J Vickers
    Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    J Soc Integr Oncol 6:82-5. 2008
  2. pmc Does a delay between diagnosis and radical prostatectomy increase the risk of disease recurrence?
    Andrew J Vickers
    Department of Urology, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Cancer 106:576-80. 2006
  3. pmc Multiple assessment in quality of life trials: how many questionnaires? How often should they be given?
    Andrew J Vickers
    Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    J Soc Integr Oncol 4:135-8. 2006
  4. pmc How to measure quality of life in integrative oncology research
    Andrew J Vickers
    Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    J Soc Integr Oncol 4:100-3. 2006
  5. pmc Living proof and the pseudoscience of alternative cancer treatments
    Andrew J Vickers
    Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    J Soc Integr Oncol 6:37-40. 2008
  6. pmc Modified technique for neurovascular bundle preservation during radical prostatectomy: association between technique and recovery of erectile function
    Timothy A Masterson
    Department of Surgery, Urology Service, Memorial Sloan Kettering Cancer Center, New York, NY10021, USA
    BJU Int 101:1217-22. 2008
  7. pmc Decision curve analysis: a discussion
    Ewout W Steyerberg
    Department of Public Health, Erasmus University, Rotterdam, The Netherlands
    Med Decis Making 28:146-9. 2008
  8. pmc Which botanicals or other unconventional anticancer agents should we take to clinical trial?
    Andrew J Vickers
    Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    J Soc Integr Oncol 5:125-9. 2007
  9. pmc How to improve accrual to clinical trials of symptom control 2: design issues
    Andrew J Vickers
    Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    J Soc Integr Oncol 5:61-4. 2007
  10. pmc How to improve accrual to clinical trials of symptom control 1: recruitment strategies
    Andrew J Vickers
    Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    J Soc Integr Oncol 5:38-42. 2007

Scientific Experts

  • A Vickers
  • Ewout W Steyerberg
  • Timothy A Masterson
  • James A Eastham
  • John P Mulhall
  • Angel M Serio

Detail Information

Publications16

  1. pmc Basic introduction to research: how not to do research
    Andrew J Vickers
    Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    J Soc Integr Oncol 6:82-5. 2008
    ..As such, it is doubly important that clinical research is conducted by those with appropriate training, statistical help, and institutional support...
  2. pmc Does a delay between diagnosis and radical prostatectomy increase the risk of disease recurrence?
    Andrew J Vickers
    Department of Urology, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Cancer 106:576-80. 2006
    ..In the current study, the authors evaluated whether time from biopsy to radical prostatectomy (RP) was predictive of postoperative biochemical disease recurrence (BCR)...
  3. pmc Multiple assessment in quality of life trials: how many questionnaires? How often should they be given?
    Andrew J Vickers
    Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    J Soc Integr Oncol 4:135-8. 2006
    ..Decisions about the appropriate number of assessments to use can be based on statistical properties derived from simple formulae...
  4. pmc How to measure quality of life in integrative oncology research
    Andrew J Vickers
    Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    J Soc Integr Oncol 4:100-3. 2006
    ..In many cases, it is preferable to use specific symptoms, such as pain or fatigue, as opposed to more generic quality of life scales...
  5. pmc Living proof and the pseudoscience of alternative cancer treatments
    Andrew J Vickers
    Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    J Soc Integr Oncol 6:37-40. 2008
    ..It also suggests that little progress has been made in the conventional treatment of myeloma. This is highly misleading and may lead to cancer patients rejecting effective treatments...
  6. pmc Modified technique for neurovascular bundle preservation during radical prostatectomy: association between technique and recovery of erectile function
    Timothy A Masterson
    Department of Surgery, Urology Service, Memorial Sloan Kettering Cancer Center, New York, NY10021, USA
    BJU Int 101:1217-22. 2008
    ..To prospectively evaluate whether a modified surgical technique for neurovascular bundle (NVB) preservation during radical prostatectomy (RP) is associated with an improvement in erectile function (EF) recovery after RP...
  7. pmc Decision curve analysis: a discussion
    Ewout W Steyerberg
    Department of Public Health, Erasmus University, Rotterdam, The Netherlands
    Med Decis Making 28:146-9. 2008
  8. pmc Which botanicals or other unconventional anticancer agents should we take to clinical trial?
    Andrew J Vickers
    Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    J Soc Integr Oncol 5:125-9. 2007
    ....
  9. pmc How to improve accrual to clinical trials of symptom control 2: design issues
    Andrew J Vickers
    Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    J Soc Integr Oncol 5:61-4. 2007
    ..Patient burden can be reduced by limiting the number of hospital visits and avoiding excessive numbers of questionnaires...
  10. pmc How to improve accrual to clinical trials of symptom control 1: recruitment strategies
    Andrew J Vickers
    Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    J Soc Integr Oncol 5:38-42. 2007
    ..The information given to patients during any initial contact should be as simple and general as possible: presenting too much information too soon can be overwhelming and off-putting...
  11. pmc Setting the bar in phase II trials: the use of historical data for determining "go/no go" decision for definitive phase III testing
    Andrew J Vickers
    Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Clin Cancer Res 13:972-6. 2007
    ..We sought to determine the proportion of phase II trials that require historical data to establish the null and to determine how these historical estimates were derived...
  12. pmc Decision curve analysis: a novel method for evaluating prediction models
    Andrew J Vickers
    Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, USA
    Med Decis Making 26:565-74. 2006
    ....
  13. pmc How to randomize
    Andrew J Vickers
    Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    J Soc Integr Oncol 4:194-8. 2006
    ..Computer randomization can easily incorporate extensions of randomization, such as blocking, stratification, and minimization, which can help ensure balance between groups...
  14. pmc How to design a phase I trial of an anticancer botanical
    Andrew J Vickers
    Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    J Soc Integr Oncol 4:46-51. 2006
    ..Increasing the use of phase I methodology would ensure a more systematic development of botanicals as anticancer agents. This would likely increase the chance that at least one such agent would be proven to extend lives...
  15. pmc Unconventional anticancer agents: a systematic review of clinical trials
    Andrew J Vickers
    Integrative Medicine Service and Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    J Clin Oncol 24:136-40. 2006
    ..The objective of this study was to review systematically the methodologies applied in clinical trials of unconventional treatments specifically for cancer...
  16. pmc Phase II designs for anticancer botanicals and supplements
    Andrew J Vickers
    Department of Epidemiology, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    J Soc Integr Oncol 7:35-40. 2009
    ..Such a design asks whether patients treated by the new agent are doing better than expected; if so, this suggests that the agent should be tested further in phase III trials...