Case Report Form (CRF) - Clinical Trials

The ICH GCP Guidelines say: The reason for having CRFs in a study is to (collect the necessary information about:

• the patients
•  the administration of the study drug
• the outcome of the assessments.

CRFs are the official documentation of the trial for the authorities, and together with the source documents will be closely examined during audits and inspections.The data on the CRFs will be entered into a computer system and the statistical analyses will then be performed. The data on the CRFs is therefore the basis for the trial report and also for any publications, as well as making up part of the data for regulatory approval of a new drug.

When completing the form use a black ball point pen to complete the CRF. If the CRFs are printed on carbonless duplication paper, always make sure that a suitable separator is inserted under the form being completed. If for some reason you cannot complete part of the form, you shouldn’t just leave a blank space ~ this is impossible for the people doing the data entry into the computer to interpret. Instead write unknown, uncertain, missing or test not donr as appropriate, or similar unambiguous words. Avoid using the ambiguous phrase, ‘not available’.The CRFs must be signed where indicated by the Principal Investigator to indicate that
he/she believes they are complete and correct. Some Sponsors require a signature on each page of the CRF, some only a signature on the final page.

Ensure legibility of all data entries. Corrections should be made as follows:

• Cross out the incorrect entry with a single line - the incorrect entry should still be readable, on no account use liquid correcting fluid.
• Enter the correct data.
• Initial and date the correction, and give an explanation of the correction if it is not obvious why it was changed.

Informed Consent form- Signature

The consent form should be signed and dated by the following people:

• A medically qualified person providing the information, this being the Investigator
• The subject.
•  A witness, if this is possible and if required for the study. 

A witness is defined as someone who records that the subject has provided consent of their own free will and has been fully informed of the study. The best witness is a subject’s friend or family member who has sat in when the study was being explained to the patient. A witness must have no vested interest in the study; therefore a research assistant/SSC/Sub-Investigator is not suitable as a witness.All signatures should be dated by the person who is signing and under the signature or Sub-Investigator. they should write their name in block capitals.

Obtaining Personal Written Informed Consent during Clinical Trials

When describing the study the physician /SSC should cover the following:

•  That it is a research procedure, and which aspects are experimental - it may or may not be beneficial to the subject - e.g. placebo.
•   The purpose of the trial.
•  Details about the drug under investigation. If there is a placebo arm to the study, this must be carefully     explained.
• The design of the trial, for example ‘double dummy’ or ‘crossover’. Often a
•  The number of people involved.
•  Duration of the trial. If the trial is a long-term one, enthusiasm is required.
•  Number of visits involved and duration of the visits. The area where the patient will be seen and by whom.
• Procedures involved, for example blood tests, ECGs, urine samples and chest x-rays - how many and how often.
•  The responsibilities of the subject if he/she participates.
•  Out of pocket expenses and the receipt procedure. If a taxi account is set up for thestudy, then this will be explained. If payments are entailed, the details must be covered, including the arrangements for pro-rated payments.
•  The risks involved to the subject and any benefit that might be expected. If no clinical benefit is intended, the subject must be told.
• Questions about the patient’s medical history will be asked and disclosure of all medication the patient is taking, which will be kept up to date if changes occur.
• Alternative procedures or treatments.
• If the study has a specific exclusion criterion, for example a left ventricle ejection fraction <350/0, but this is measured only after the patient has given written consent, this exclusion will be carefully explained, Providing written informed consent does not mean definite progression into the study.
• The availability of compensation and treatment if needed.
• That, because it is a study, written consent is needed which is voluntary and there is no penalty for refusal.
• The right to withdraw from study medication at any time without affecting their future medical care. Similarly, if the Investigator thinks that the study medication is not suiting the patient, then the medication would be stopped.

Patient Recruitment- Clinical Trials

The first step is to define exactly what is meant by patient recruitment. This is not as straightforward as it sounds. There are several steps from the patient being identified and contacted to starting the study treatment. These include screening the patient, obtaining informed consent. randomising the patient, a possible baseline assessment and then initiation of treatment. Exactly when the patient is said to be enrolled in the trial should be
defined in the protocol.The recruitment period, i.e. starting and finishing date of recruitment for the entire study, may also be defined in the protocol.

Intention to Enrol list:For the purpose of this SOP, an ‘Intention to Enroli st’ is a record of all patients who were considered, were eligible for the study, but who, for one reason or another, were not included. This list enables a comparison of the potential patient population with the patient population actually enrolled in the study. It is helpful when questions of bias arise during evaluation of the data.