Clinical Trials Services Section
Hospitais da Universidade de Coimbra
Research into new molecules has brought us more effective and safer drugs, which have improved the treatment of patients and their quality of life. The process of drug research has two stages: first the investigation and development of the agent until its approval for use and then the postauthorisation stage. The first stage has the following steps:
- Preclinical development:
– Obtaining the new molecule.
– Activity screening.
– Formulation and production of the new agent.
- Clinical research.
- Register for marketing approval.
The main objectives of this stage are to establish the quality, safety and primary efficacy of the drug. For the second stage of drug research, the goal is to overcome the limitations of the controlled experimental studies.
Protection of the trial subjects and credibility of the research are the greatest responsibilities of the healthcare professionals who are part of the investigation team. Clinical research in hospitals must be undertaken by a multidisciplinary team to ensure effective development and implementation of clinical trials. Pharmacists can, and should, be involved in the process, either as members of the ethics committee or as part of the investigation teams that carry out the trial. Pharmaceutical services must be responsible for all the drugs under investigation in the hospital, and the clinical trial drug and devices distribution system must be centralised to ensure security, efficacy, efficiency and reliability of the process.
Active participation of the pharmacist in clinical trials is invaluable for the correct receipt, storage, distribution and control of the clinical trial drug – tasks already performed by the pharmacy for other drugs used in the hospital. Some of the clinical activities carried out by pharmacists can contribute to better data collection for the studies.
The pharmacist, as a member of the investigation team, in addition to their responsibility towards the study drug itself, may also be involved in other aspects of the study, such as:
- Randomisation of the subjects.
- Providing information/training for the subjects.
- Protecting the study’s blindness.
- Drug preparation.
- Administration of quality-of-life questionnaires.
- Custody of treatment codes.
Before the trial
Pharmaceutical services should develop structures and procedures that allow the control of the drugs used in clinical trials. Protocols must: ensure the security of the drug; set out the responsibilities of the people involved; include the ability to track down who did what and when; and control information access by authorised personnel. Internal procedure protocols must be developed for all those involved in the clinical trial (doctors, nurses, patients and pharmacists). Procedure protocols are needed for the use of investigational drugs, for situations not projected. Protocols must also be in place for drugs not stored under the supervision of a pharmacist.
The right equipment (eg, cabinets or fridges) must be available for storage of the clinical trial drug at the correct temperature and humidity.
The initial meeting
Following authorisation from the administration board for the clinical trial to proceed, a meeting takes place with the trial sponsor, the principal investigator and the hospital pharmacist. At that meeting the following matters are usually discussed:
- The date for the delivery of the clinical trial material.
- The date for the beginning of the study.
- The date for the first monitoring visit, usually at the time of the introduction of the first subject into the clinical trial.
- The clinical trial drug distribution procedures, whether directly to the subject, investigator or nurse.
- Proceedings regarding the clinical trial material reconciliation.
- Internal procedure protocols development (prescription, distribution, information preparation, administration, reconciliation, etc). These protocols, developed in accordance with the clinical trial protocol, are adapted to the hospital’s circumstances. Their objective is to assure safety in the distribution, preparation, administration and reconciliation of the clinical trial drug, thus allowing the documentation of all the data necessary for fulfilling the clinical trial protocol regarding the drug.
During the trial
A continuously updated file on the drugs, investigators, sponsors and clinical trial subjects must be maintained. In addition, the pharmacy should keep a copy of the ethics committee approved protocol, the investigators’ manual, all ethics committee approved modifications, the ethics committee report, national regulatory drug entities’ authorisation and the analytical certificates for the batches of the clinical trial drug. Costs and expenses associated with the trial must be documented.
Receipt of the trial drug
When the clinical trial drug arrives in the department, verification of the packaging and transport conditions, quantities received, batches, retest date, general condition and release statements is essential.
Figure 1 illustrates the clinical trial drug circuit within the hospital.
The pharmacist must ensure there are no breaks in the supply of the drug to the subjects and place a label stating “for clinical trials only” when the trial drug is distributed.
When providing information at the time of drug distribution, it is important to ensure therapeutic adherence and compliance with the administration protocols. Therefore, at the time of dispensing make sure that, if the trial drug is given directly to the clinical trial subjects, it is preceded by an interview with the goal of informing them that they are participating in a clinical trial, with rights and duties, the way to take the drug, its storage, the information they should give to their general practitioner regarding the drug they are taking, which drugs they should not take, and they have the responsibility to return all the unused medication, as well as all packaging, with or without the drug. Register the subjects’ drug history at that time. This information should be transmitted throughout several appointments.
If the trial drug is given directly to the investigators, remind them of all the precautions that the patients should have regarding the drug’s administration and its storage and that they should always return all the medication left and empty packages. If given directly to the nurses, they must be informed of all these things. All of the clinical trial injectable drugs are prepared by the pharmacist and are delivered ready for administration.
Reconciliation of the clinical trial drug to the sponsor should be preceded by tracing the circuit of the drug during the time it was kept in the hospital.
At the end of the trial
At the end of the study it is necessary to inform the patient what will happen to them after the clinical trial is over, what they are entitled to and how to get it. The most frequent concern of the patient is, “I am feeling all right now. How will I keep receiving the drug?”
When compiling internal reports for the principal investigator, pharmaceutical services administration, ethics committee and hospital board, pharmacists should include objective information about all that took place during the study, not only regarding the drug used (quantity received, given to patients, returned to sponsor, costs, etc) but also more personal aspects concerning the clinical trial subjects.
The pharmacist should actively participate in clinical trials as a member of the ethics committee in the clinical trial approval stage and as a member of the investigation team during the clinical trial itself.
In the first instance, the pharmacist, as a member of the ethics committee, contributes knowledge from a clinical point of view as well as directly regarding the drug, its chemical structure, indications and side-effects, which increases the authority of the decision made, whether positive or negative, to proceed or not.
The presence of a member of the pharmacy department on the ethics committee also allows the rest of the department to be kept updated concerning the clinical trials that are taking place within the hospital, which may have implications for the future of therapeutics.
During the clinical trial, the pharmacy department must be responsible for centralising all processes involving the trial drug. A clinical trials section should be created within the department for that sole purpose.
The pharmacist must play a part in the investigation team, being necessarily responsible for the management of both the clinical trial drug and medical devices used for its administration and preparation. They should also take an active part in clinical activities related to the study.
- Bonal J, Alfonso Dominguez G. Farmácia Hospitalaria. 2nd ed. Médica Internacional; 1992.
Fortner CL. Investigational drugs in the hospital. In: Handbook of institutional pharmacy practice. 3rd ed. American Society of Hospital Pharmacists, Inc; 1992.
ASHP guidelines for the use of investigational drugs in organized health-care settings. Am J Health-Syst Pharm 1991;48:315-9.