New drugs developed to treat diseases go through several clinical trials before they can be sold. A Phase 0 clinical trial is the first stage of testing a new drug on a small sample of 10 to 12 volunteer patients.
The volunteer patients chosen by the contract research organization for this early clinical trial are generally in good health rather than individuals who are suffering from a medical condition which the drug is intended to treat.
The risks for using the drug are unknown at early stages of clinical trials and a very low dosage is administered for a duration of under 10 days in order to minimise harmful side effects which the drug may cause among volunteers.
Goal of Phase 0 Trials
Rather than testing the therapeutic effects of a drug, the goal of Phase 0 clinical trials is to check that patients respond as expected to a drug being tested. Preliminary data is also gathered to examine how a drug affects the body and how the body responds to the drug.
The other objective of Phase 0 clinical trials is to rank the drugs being tested, and shortlist the ones which will be tested in subsequent phases. Drugs which progress to the next phase of trials are tested by the clinical research organization in increasing dosages so that a safe dosage regimen can be established.
Before Phase 0 clinical trials can be administered they require extensive characterization of the agent and development of target assay. The goals of Phase 0 clinical trials can also include the assessment of the pharmacokinetic-pharmacodynamic relationship of the drug being investigated.
Based on the outcome of phase 0 clinical trials by a contract research organization, a pharma company acquires information to decide whether the clinical trial of the drug can be developed to begin the next phase of trials. The positive outcome anticipated from a Phase 0 clinical trial should be a benefit to the broader society in terms of scientifically valid drug development.
It covers the transition from a preclinical to clinical drug development which includes an assessment of the effect of the drug on the surrogate or target.
Perspective of Patients
From the perspective of a patient, Phase 0 clinical trials offer an opportunity to improve the way to evaluate some drugs.
Involvement of patients helps a clinical research organization to quickly identify treatment options either to discard drugs which don’t appear to work or to take promising drugs to the next stage.
Volunteers act as participants rather than research subjects. They play an important role in searching for ways to improve the detection, diagnosis, treatment and ultimate prevention of life threatening diseases.
Risk and Ethical Considerations
There are important ethical concerns which need to be taken into account when conducting Phase 0 clinical trials. These include the risk-benefit ratio, lack of intent for treatment and a participant’s understanding of the consent document. The successful execution of Phase 0 clinical trials requires attention to these issues.
The risk that potential interventions will be required and the limited nature of the clinical trial are challenges for participation in Phase 0 clinical trials.
Prior patient-physician relationship and the general understanding a participant has about clinical trials are important factors to be considered when approaching eligible patients for enrolling in Phase 0 clinical trials.
The risk to patients and risk-to-benefit ratio of Phase 0 trial are important considerations. Additional participation risks are those from research related interventions. These include serial tumour biopsies as well as computed tomography scans in addition to the possibility of future exclusion from participating in further clinical trials which offer the likelihood of a therapeutic benefit.
Volunteer patients who enrol in Phase 0 clinical trials need to understand that they will not have a medical benefit from the trial. Samples obtained for research from participants should be used in validated assays to establish whether the drug being evaluated is having the intended effect.
This knowledge could improve the efficiency and quality of subsequent clinical development of the drug under investigation, making it available much more quickly for patients in the future.
The clinical research organization should consider the benefits and risks involved for patients who are considering participation and may be vulnerable because of their health or competence.