Quality assurance in early phase clinical trials plays an important role in minimizing potential risk to volunteers or patients who take part in these types of studies and may help to eliminate potential problems before they occur.

The ICH-GCP principles for clinical trials are applied for early phase clinical trials the same, but some specific points that should be considered while auditing or managing early phase units. The three key factors for the successful operations in the early phase units combine professional staff, proper facilities and equipment, and the administration of healthy volunteers.

Professional staff

The first factor leading to success in early phase clinical trials is experienced, trained, and dedicated staff. Indeed, they are key to the safety of volunteers or patients in early phase trials. Proper resourcing and allocation of staff to the trials is an important aspect of the unit’s day to day function.

Enough staff should be available during dosing days for multiple PK sampling or other procedures to be performed in very tight timelines. Some protocols require an overnight stay and long-term stay, so, night/weekend shifts of doctors and nurses should be planned.

Specific requirements for Principal Investigator/Sub Investigator’s qualification in early phase trials should be followed per local legislation: e. g., medical license within the therapeutic area of the trial, previous experience in Phase I/Bioequivalence studies, or license of Clinical Pharmacologist.

Facilities and equipment

As facilities and equipment affect the progress of clinical trials, the Phase I unit should be located within a hospital environment with the critical care facilities available. For standalone units, 24/7 access to the hospital emergency response team should be available within minutes.

Appropriate emergency equipment should be available and procedures for handling medical emergencies should be in place. The staff should be trained in life support and how to use emergency equipment. Early phase units should be equipped with alarms in any areas where subjects have access (wards, showers, bathrooms, canteen, and recreational areas). Alarms should be regularly tested and the evaluation should be documented. One more important point to consider for early phase trials: synchronized clocks should be placed in procedure areas for accurate PK sampling, dosing, vital signs measurement.

Administration of healthy volunteers

Healthy volunteer identification and taking care of them is a third key factor in early phase units. To enroll the required number of subjects is a challenge in every clinical trial. The early phase units usually have their database of healthy volunteers. Three points to consider on the proper administration of healthy volunteers:

• A recruitment strategy should be developed for every trial separately with the prevention of “over-volunteering” considered.
• All advertisements for recruitment should be approved by the Ethics Committee before using them.
• The consenting of healthy volunteers for personal data processing should be properly documented to meet data protection requirements.

When a potential subject comes to the site, he/she should provide his/her passport or ID card. The site should have a procedure to check the subject’s identity for every visit to ensure the same subject has consented and the same subject is being dosed. Bracelets with subject ID number should be used during study visits, and the staff should check the subject’s ID before conducting any procedure.

Consenting procedure for healthy volunteers or patients in early phase trials is conducted per GCP guidelines and local regulations. Special attention should be paid to potential trial risks (especially in first-in-human trials), protocol compliance: e.g., long-term stays in the unit, restrictions for diet, smoking, alcohol consumption.

Compensation for participation in the trial is an additional topic during the informed consent procedure. The compensation scheme per local regulations should be approved by the Ethics Committee and documented in the Informed Consent Form.

A few more important things to consider for early phase units to ensure a safe and friendly environment: controlled access to the unit, locked windows, fire security system, and emergency exits, sufficient space for leisure, Wi-Fi, TV, books, magazines, board games, etc. And, of course, compliance with the protocol procedures, proper medical care, and protection of the subject’s rights is a benchmark for every clinical trial.

Here are outlined only a few points that should be considered for early phase units. Please refer to the international guidelines and local legislation for further guidance for these types of units.

Saulenė Kudarauskaitė, MD

Quality Assurance Manager

BIO1 Early Phase Unit

References:

1. Annex V to Guidance for the conduct of Good Clinical Practice inspections. Phase I Units.
2. MHRA Phase I Accreditation Scheme, Version 3.