7. Remote Monitoring

Section 13.1.3 “Trial Monitoring”, under section 13.1 “Decentralized Elements in Spain” within the AEMPS Instruction Document, provides the following information:

“Remote verification of source data shall be considered for all ongoing clinical trials as long as it is carried out with all the safeguards and precautions shown in the directives of the UE and with the requirements established by the Spanish Data Protection Agency, and therefore shall require the prior approval of each site with the approval of the data protection delegate of the same. 

Previous approval will not be required for a substantial amendment by the CEIm nor the authorization of the AEMPS. Neither will it be necessary to have the patient's express consent to carry out the verification of source data during remote monitoring.”

7.1 eConsent/Remote Consent

Spanish authorities allow the use of electronic consent as well as electronic signatures as long as those are in compliance with the requirements of Advance Signatures as per the eIDAS regulation 910/2014.

Section 13.1.1 Informed Consent on the AEMPS Instruction Document provides the following information regarding electronic consent:

“13.1.1 Informed consent

 As part of the process of obtaining informed consent, it is considered essential that face-to-face communication takes place between the potential trial participant and the investigator, or a qualified person designated by the investigator. If this discussion is done in a digital/virtual meeting, it is recommended that this takes place in real-time where the parties can both see and communicate with each other via audio and video.

Consent must be obtained preferably in writing. However, in exceptional and justified circumstances it is permissible to get the consent orally (for example, by telephone or video-call), documenting it in the patient's medical records and ratifying it later in writing by means of the patient's signature and that of the investigator. The principal investigator or the person who has been designated by him/her must send the patient information sheet (PIS) to the patient by email or courier. The later ratification in writing by means of the patient's signature and that of the investigator can be carried out by mail, by audio-visual means, or by digital images. The patient can send the scanned, signed PIS by email, or can take a photo of the signed consent and send it to a telephone only accessible to the research team. This image file must be printed out and maintained in the investigator's file as proof of signature." 

7.2 eSignature (including any requirement for a countersignature (e.g. PI, witness, etc.)

Electronic informed consent is possible as long as it is obtained with a high-security level signature, in accordance with eIDAS Regulation nº 910/2014, and confidentiality and security of personal data, as well as secure access, is guaranteed. Only this type of signature meets the specifications, procedures, or controls to avoid the misuse or alteration of the identity. 

EMA’s “Guideline on computerized systems and electronic data in clinical trials” and chapter 3 of EMA’s “Recommendation paper on decentralized elements in clinical trials” should be taken into consideration too. The entire procedure for obtaining informed consent should be described step-by-step in the clinical trial application, part II, to ensure appropriate CEIm ethical review.

7.3 Remote Assessment

While Spanish Authorities have not made any reference to remote assessments, EMA’s “Recommendation paper on decentralized elements in clinical trials” makes some remarks with regard to remote assessments. See below:

"In clinical trials with decentralized elements, parts of the clinical trial may be conducted outside the traditional patient care centers, with the involvement of service providers. General medical rules to protect patient/trial participant’s safety should be upheld in trials with decentralised elements especially when patients/trial participants are separated from traditional patient care centers. Among those is the assessment of individual patient’s risk profile, including appropriate anamnestic information, physical examination, and laboratory or imaging data by a responsible investigator with the required trial population-specific medical background. Exceptions should be justified in the clinical trial application to ensure appropriate case-by-case review. 

When parts of the clinical trial are conducted off-site, and when additional service providers such as home nurses or providers of technology become involved, it is essential that the specific roles and responsibilities of the sponsor, investigator, and any additional parties are clearly defined and understood prior to the start of the trial. In addition, when trial participants are visiting the clinical trial site less frequently, alternate methods of clinical monitoring of the trial participants’ current health status and related data collection may need to be utilized. Data may be received from different routes, for example, collected at home by the participants themselves, by visiting (external) healthcare professionals, or by digital tools. This poses a challenge to the oversight on the rights, safety, dignity, and well-being of the trial participants as well as the reliability of trial results. As a general concept, introducing decentralized elements should be considered as an extension of the clinical trial site with the inclusion of the trial participants’ home, resulting in an additional obligation of oversight for investigators and sponsors. It is therefore important that, when decentralized elements are implemented, it is ensured that the investigator and sponsor still can fulfill their legal obligations as laid down in the CTR or the CTD and ICH E6. In addition, with a potential increase in the number of parties involved in the clinical trial, adherence to the GDPR needs to be safeguarded."

7.4 Electronic Patient Reported Outcome (ePro) 

This is not specifically addressed in the national legislation; however, Spanish CA and EC accept the use of ePROs within clinical trials.

The EMA's “Recommendation paper on decentralized elements in clinical trials” makes some remarks with regard to ePROs. See below:

The trial participant should be fully informed in advance on how the information transmitted via digital tools, for example, electronic Patient Reported Outcomes (ePROs), will be acted upon. It should be made clear to the trial participant that the investigator may not review such data in real time, and that if the trial participant experiences any specific safety concern they need to directly contact the investigator to report such an issue.

ePROs considerations are also reflected within the EMA guidance on “Computerized Systems and electronic data in clinical trials”.

7.5 HHC – Home Nursing

The EMA provides considerations of trial-related procedures that can be conducted at home, within section 5 of the “Recommendation paper on decentralized elements in clinical trials”.

Summary of those recommendations are:

• Investigator to ascertain suitability for trial procedures to be conducted at the participant’s home.
• Inclusion/exclusion criteria should include provisions related to the adequacy of the participant’s home.
• Participant should be informed during the consent process about planned trial procedures conducted at their home.
• Trial-related procedures at home should only be done if the procedures do not cause additional risk to trial participant or reliability of the data and the person performing the task is qualified and/or trained to perform the task. 
• The sponsor and/or investigator should ensure that appropriate guidance and training are provided to the delegated person(s) to conduct the tasks at home correctly. 
• The insurance or indemnity or a guarantee or a similar arrangement foreseen by CTR or the CTD should be in place to cover any damage resulting from trial-related procedures performed at home. 
• Investigator should monitor compliance of the trial participant considering the lack of/decrease in the number of face-to-face visits/meetings between the trial participant and the investigator and/or delegated staff. 
• Trial participants should be given the opportunity to visit the investigator in person if needed/preferred and they should be able to have a direct contact line if further support to perform a trial-related task/collect data is needed. 
• There should be procedures in place for reporting and management of adverse events noticed by the trial participant or by any delegated person during home visits.
• The sponsor should provide alternatives if a trial participant is unable or not willing to use her/his/their own private device (mobile phone, tablet, etc.) to capture trial data. 

7.6 HHC – Home Lab Collection

Collection of biological samples at home is permitted, as long as the procedures involved do not cause any additional risk to trial participants or reliability of the date and the person performing the task is qualified and/or trained to perform the task. If biological samples are collected at home, it should be considered whether persons taking the sample are qualified and allowed by their local legislation to take the sample. In addition, adequate handling and storage conditions for the samples throughout the entire process should be assured.

There may be country-level additional requirements such as IATA training for handling infections and biological material.

7.7 Remote Monitoring

Section 13.1.3 “Trial Monitoring” under section 13.1 “Decentralized Elements in Spain” within the AEMPS Instruction Document provides the following information:

“Remote verification of source data shall be considered for all ongoing clinical trials as long as it is carried out with all the safeguards and precautions shown in the directives of the UE and with the requirements established by the Spanish Data Protection Agency(7), and therefore shall require the prior approval of each site with the approval of the data protection delegate of the same. 

Previous approval will not be required for a substantial amendment by the CEIm nor the authorization of the AEMPS. Neither will it be necessary to have the patient's express consent to carry out the verification of source data during remote monitoring.”

7.8 Telemedicine

While not specifically addressed in the national legislation, telemedicine is permitted in Spain.

Ethics Committees tend to enquire about the privacy settings of any platform used for telemedicine purposes.

7.9 Wearables

Wearables are not specifically addressed in the existing national legislation, but support for their use may be found in the EMA's “Recommendation paper on decentralized elements in clinical trials” which makes some remarks with regards to wearables as part of handling data. References to Wearables as well as Bring Your Own Device (BYOD) can also be found within the EMA guidance on “Computerized Systems and Electronic Data in Clinical Trials”.