A designated sponsor organization has ultimate responsibility for a clinical trial, including responsibility for the quality and integrity of trial data.

Sponsors’ responsibilities include:

  • Ensuring that clinical trials are carried out in accordance with Good Clinical Practice (GCP) and international quality standards (e.g. ISO 9001).
  • Ensuring appropriate oversight of all trial-related functions carried out on its behalf.
  • Ensuring that qualified medical personnel are readily available to advise on any medical issues that arise during the trial.

A sponsoring organization may carry out a study itself or transfer any or all sponsor trial-related responsibilities and functions to a contract research organization (CRO).

It is essential for a sponsoring organization to have its own experienced clinical pharmacologist and clinical operations specialist (distinct from the CRO clinical team) to represent its interests during the conduct of the trial.  These individuals may be employees, consultants or contractors.

Planning a phase 1 trial

The design of a phase 1 trial is initially developed within the sponsoring organization, in the form of a synopsis. This is an overview of the planned trial, covering the study’s aims, objectives, types of participants, endpoints and the experimental studies to be carried out to obtain extra information about an investigational drug.

A synopsis is typically reviewed by experts and discussed with potential CROs, if a study is being outsourced. Once a synopsis has been agreed and a CRO selected, a more detailed clinical trial protocol is developed. This details exactly what studies are to be carried out and how they are to be conducted.

The protocol is a critical element of a clinical trial. It must be approved by regulatory authorities and must be closely adhered to during the trial. If a need arises to adapt a study design, a specific protocol amendment must be agreed with regulatory authorities.

Designing a phase 1 trial

The critical aspects of a phase 1 trial include dose selection, dosing strategy and choice of endpoints (clinical and laboratory).

A phase 1 first in human (FIH) study usually follows a double-blind, randomized, placebo-controlled, dose escalation design. This design minimizes bias through blinding and randomization, provides a comparison of safety with respect to no treatment (placebo), and minimizes potential risks by initially evaluating the safety of low doses.

Endpoint selection

FIH studies are designed to assess safety, tolerability and pharmacokinetics. The specific methods to be used in their assessment, including the timing of data collection, must be included in the trial protocol.

Safety evaluation typically includes physical examination, vital signs, adverse events, laboratory safety testing, electrocardiograms, and any compound-specific safety measurements identified as potential risks in preclinical development studies.

Tolerability evaluation aims to assess the degree to which the presentation or side effects of a drug affect the willingness of a participant to take a medication. Tolerability has an important impact on adherence to medication and therefore on a treatment’s effectiveness. Tolerability is determined by assessment of safety endpoints.

Trials may also aim to assess aspects of a participants’ subjective experience of a treatment, although these measures are difficult to standardize. The number of participants dropping out of a trial can also be taken as a measure of tolerability.

Pharmacokinetic assessments are undertaken to improve understanding of an administered drug’s distribution within the body, including at sites of infection. This will generally require measurement of drug levels in the blood and potentially other tissues at different time points after drug administration. Binding to plasma proteins should also be assessed, so that circulating levels of available drug can be determined.

Studies typically also assess metabolism of a drug (e.g. within the liver) and its elimination from the body (generally in urine via the kidney).

For orally administered drugs, a FIH study should assess whether drug exposure is influenced by food intake at the time of dosing (food effect).