1. Provisions and prerequisites for a clinical trial

1.1. Justification for the trial

It is important for anyone preparing a trial of a medicinal product in humans that the specific aims, problems and risks/benefits of a particular clinical trial be thoroughly considered and that the chosen solutions be scientifically sound and ethically justified.

1.2. Ethical principles

All research involving human subjects should be conducted in accordance with the ethical principles contained in the current version of the Declaration of Helsinki and should respect three basic ethical principles, namely justice, respect for persons, beneficence (maximize benefits and minimize harms and wrongs) and non-maleficence (do no harm) as defined by the current revision of the International Ethical Guidelines for Biomedical Research Involving Human Subjects issued by the Council for International Organizations of Medical Sciences (CIOMS) or laws and regulations of the country in which the research is conducted, whichever represents the greater protection for subjects. All individuals involved in the conduct of any clinical trial must be fully informed of and comply with these principles.

1.3. Supporting data for the investigational product

Preclinical studies that provide sufficient documentation of potential safety and eventual clinical application of a pharmaceutical product are a necessary prerequisite for a clinical trial. Information about manufacturing procedures and data from tests performed on the actual product should establish that the product is of suitable quality. The pharmaceutical, preclinical and clinical data should be adapted to the appropriate phase of the trial, and the amount of supporting data should be appropriate to the size and duration of the proposed trial. In addition, a compilation of information on safety and efficacy collected in previous and ongoing clinical trials elsewhere with the investigational product is vital for the planning and conduct of subsequent trials.

1.4. Investigator and site(s) of investigation

Each investigator should have appropriate expertise, qualifications and competence to undertake a proposed study and be familiar with pharmacokinetic theories underlying bioavailability studies. Prior to the trial, the investigator(s) and the sponsor should establish an agreement on the protocol, the monitoring, the auditing and on standard operating procedures (SOP), and the allocation of trial-related responsibilities. The logistics and premises of the trial site should comply with requirements for the safe and efficient conduct of the trial.

1.5. Regulatory requirements

Countries in which clinical trials are performed should have regulations by which these studies can be conducted. The pre-trial agreement between sponsor and investigator(s) should designate the parties responsible for meeting each applicable regulatory requirement (e.g. application, protocol amendments, adverse reaction reporting, notifications to ethics committee). All parties involved in a clinical trial should comply fully with the existing national regulations or requirements. In those countries where regulations do not yet exist or require supplementation, the relevant government officials may designate, in part or in whole, the WHO Guidelines for Good Clinical Practice as the basis on which clinical trials will be conducted.

2. The protocol

The clinical trial should be carried out in accordance with a protocol agreed upon and signed by the investigator and the sponsor. Any change(s) subsequently required must be similarly agreed on and signed by the investigator and sponsor and appended as amendments. The protocol and attachments/appendices should state the aim of the trial and the procedures to be used; the reasons for proposing that it should be undertaken on human subjects; the nature and degree of any known risks; the groups from which it is proposed that trial subjects be selected and the means for ensuring that they are adequately informed before they give their consent.

The protocol and attachments/appendices should be scientifically and ethically appraised by one or - if required by local laws and regulations - more, review bodies (institutional review board, peer review committee, ethics committee, drug regulatory authority, etc.), constituted appropriately for these purposes and independent of the investigator(s) and sponsor.

(For additional information see WHO Guidelines for Good Clinical Practice (GCP) for Trials on Pharmaceutical Products.)