| Issue / problem |
Approaches |
| Patients as research subjects |
Recognize patients as participants and contributors in research rather than research subjects
Share study results with participants
Make results availability at publicly accessible database |
| Patient participation |
Good prior patient-physician relationship
Approach patients who have had prior clinical research participation experience
Choose Institutions with proven research orientation, research facilities and infrastructure
Increase awareness of phase 0 concept among patients and physicians community
Devise and implement an overall clinical care plan for individual patient
Discuss overall clinical care plan with patient, family and primary physician
Consider patients with advanced or metastatic disease waiting for the surgery
Consider enrollment of healthy volunteers in phase 0 trials those do not aim for the characterization of an anticancer drug in tumor tissue |
| Informed consent and therapeutic misconception |
Carefully explain to patients: non-therapeutic nature, study procedures and benefit to others
Document phase 0 trials as exploratory or experimental research rather than as clinical trials
Add an explicit statement in ICD acknowledging no personal benefit and treatment delay
Document participants’ understanding of study objectives and nature
Consider modest payment
Exclude vulnerable patient population
Include impartial witness as a general practice
Inform patients of limited preclinical testing done |
| Delayed participation in other clinical trials |
Acceptance of ≤ 2 weeks washout period of phase 0 trials in other therapeutic clinical trials
Help enroll phase 0 participants in other clinical trials without any delay
Devise and implement an overall clinical care plan for individual patient
Exclude patients requiring immediate medical care
Allow phase 0 participants in later studies of the molecule, if found beneficial |
| Study design and scientific validity |
Make full utilization of each tissue sample for the research purpose
Use validated and optimized PD assay
Confirm validity of dose extrapolations prior to study initiation
Use validates biomarker, if available
Establish and follow SOPs for assay and tissue handling procedures
Minimize possibility of invasive biopsies
Devise novel statistical designs with required power
Use scientifically justified drug doses
Consider patients with advanced or metastatic disease waiting for the surgery to merge post-treatment biopsies with typical surgical procedure |
| Unforeseen adverse effects |
Use lower doses with greater safety margin
Monitor closely of any possible adverse effect
Provide adequate medical care |
| IRB review quality and efficiency |
Seek review from IRBs experienced in phase 0 trials
Mutual acceptance of the review proposals between IRBs |
| Abbreviation: ICD, informed consent document; PD, pharmacodynamic; SOPs, standard operating procedures; IRBs, institutional review boards. |
