Phases of a Clinical Trial

A clinical trial cannot be started until it has been approved by the competent agenciess designated by law. In Spain, approvals are granted by the Spanish Agency of Medicinal Products and Medical Devices (AEMPS) and an accredited Medical Research and Ethics Committee (MREC). All clinical trial applications and communications must be addressed to the AEMPS and to the MREC that has agreed to evaluate the study. The procedure is currently centralized through the Portal of Clinical Trials with Drugs.

Clinical trial assessment application         

The assessment of a clinical trial is divided into two parts: Part I is assessed by the AEMPS and Part II, by the MREC. The assessment application must be sent simultaneously to both agencies, and can be submitted at any time of the month. For a clinical trial to be assessed, several documents must be prepared and sent.

Part I: Documents to be sent to the AEMPS and the MREC:

• Cover letter and assessment application form.
• Protocol and protocol summary.
• Investigator's Brochure or investigational drug data sheet.
• Investigator's Brochure or data sheet of secondary medications, i.e., any medications used in the study but not under investigation (if applicable).

Depending on the type of study, it may be necessary to submit other documents, as in the case of a research involving children or a low-level intervention trial (i.e., a study conducted with authorized drugs according to the indications on the data sheet that does not require a procedure entailing an added risk for patients).

Part II: Documents to be sent only to the AEMPS

These are documents strongly focused on the medications used. In the case of investigational medicinal products, they refer to Good Manufacturing Practices. All files related with the investigational drug, non-investigational medications, the labels for the study drugs, or the payment receipt of the AEMPS' fee must be submitted as well.

Part III: Documents to be sent only to the MREC:

• Document explaining the procedures and materials used for patient recruitment.
• Information sheet and informed consent given to patients to sign if they agree to participate in the study.
• Documents on investigators' qualifications and suitability of the site where the study will be conducted, as well as the résumé of the principal investigator of each participating site.
• Proof of insurance or financial guarantee of the clinical trial to cover potential risks.
• Detailed annual report.
• MREC fee payment receipt (if applicable).

Document validation.

Both the AEMPS and the MREC will notify the sponsor, within a maximum period of 10 calendar days, if the documents received are valid, also providing the corresponding assessment schedule. Should an error require correction, the applicant will have 10 days to do so, and the AEMPS and the MREC will have five days to confirm if the new submission is correct. In the event that Part I or Part II are not considered valid, the whole application will be deemed invalid.

Duration of the assessment.

The maximum assessment period of a clinical trial is of 45 calendar days from the date the application is considered valid.

Result of the assessment.

After all the documents received have been assessed, the AEMPS will inform the sponsor about the result of the assessment of Part I, which will reflect a unified decision of both the AEMPS and the MREC. Also, the AEMPS will make a decision about the trial, which can be an approval, a conditional approval, or a rejection, based on the conclusion on Part I and the MREC's decision on Part II.

Communications after approval of a clinical trial.

After a clinical trial has been approved, it can be started after signing a contract with the site where it will be conducted. Communications with the AEMPS and the MREC must be continued so they can conduct a proper follow-up of the study.

• The dates of start-up of the study, enrollment of the first patient, end of the recruitment period and end of trial shall be informed. When reporting the end of a trial, if it was terminated early, the reasons that led to this decision must be stated.
• An annual report must also be submitted, indicating the number of study patients, the visits conducted, and a detailed list of the documented side effects, whether or not related to the study drug, including the steps taken in each case, among other data. Likewise, every time a serious adverse event is detected, it will be notified immediately.
• A final summary containing the study final data must be submitted, as well as a summary of intermediate results before the end of the study (if applicable).

In order for the clinical trial data to be available at any time in the years after the end of the study, both the sponsor and the investigator will keep the content of the master file of every clinical trial, in paper or digital format, for at least 25 years after the end of the trial, or for a longer period if required by other applicable laws; for example, if the study is presented as the basis to register a medication.