Evaluation requirements

Definition

The clinical trials, according to the Royal Decree 1090/2015, are the clinical studies that meet any of the following conditions:

• The trial subject is assigned in advance to a particular therapeutic strategy, which is not part of the usual clinical practice of the Member State involved.
• The decision to prescribe medicines on research is made in conjunction with the decision to enroll the subject in the clinical trial.
• Diagnostic or follow-up procedures are applied to test subjects that go beyond standard clinical practice.

Normative

The clinical trials, according to the Royal Decree 1090/2015, are the clinical studies that meet any of the following conditions:

• The trial subject is assigned in advance to a particular therapeutic strategy, which is not part of the usual clinical practice of the Member State involved.
• The decision to prescribe medicines on research is made in conjunction with the decision to enroll the subject in the clinical trial.
• Diagnostic or follow-up procedures are applied to test subjects that go beyond standard clinical practice.

Evaluation requirements by the CEIm

The documents that must be presented for the initial evaluation of a clinical trial with mediciness are indicated in the next link: “AEMPS instructions to make clinical trials in Spain”. On the documents of the clinical trials there are two different parts, part I (documents to send to the AEMPS and the CEIm, and documents to send only to the AEMPS) and part II (documents to send only to CEIm).

The promoter must present the following documents trough the portal Clinical Trials Information System (link CTIS).

• Initial evaluation
• Substantial modification (amendment)

1. Presentation letter of the substantial modification.
2. Substantial modification solicitude form.
3. Summary and change justifications.
4. Comparative table with previous text ─ new text.
5. New version of the documents to be modified with “track changes”
6. New version of the documents to be modified in a fair copy.
7. New documents.
8. Documents supporting the changes, if applicable.
9. Billing data for payment of the assessment fee or fee waiver request.

Those clinical trials initiated under the previous regulations and submitted on the Clinical Trials Portal may submit substantial modifications under the same portal until 2025.

The management of the contract will be processed in parallel to the application by the CEIm of the Hospital Clínico Universitario de València; for this purpose, please contact the Contracts Management Area of the Foundation at the following address ensayosclinicos@incliva.es.

Favorable opinion of another CEIm

According with the provisions of Article 17 of Royal Decree 1090/2015, all clinical trials with medicinal products will require the favorable opinion of a CEIm accredited in Spain. Said opinion will be unique, binding and recognized throughout the national territory. Therefore, in these cases, the CEIm recognizes the approval and the study will not be re-evaluated. The documentation to be provided by the promoter to the CEIm of the HCUV (ceic_hcv@gva.es) is:

• Suitability of the facilities according to the model published by the AEMPS.
• Abbreviated curriculum vitae (CV) of the principal investigator.
• Declaration of conflict of interest, if not included in the CV.
• Training in good clinical practice, if not included in the CV.

The management of the contract will be processed in parallel to the application by the CEIm of the Hospital Clínico Universitario de València; for this purpose, please contact the Contract Management Area of the Foundation at ensayosclinicos@incliva.es.

Documents models

• Patients’ information sheet
• Economic report
• Proceedings and recruitment material

Definition

A medical device is any instrument, device, equipment, software, implant, reagent, material or other article intended by the manufacturer to be used on persons, separately or in combination, for specific medical purposes.

Normative

The Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices establishes the general requirements in relation to the clinical research with medical devices on chapter VI and the Annexes XIV and XV thereof. The Regulation (EU) 2022/2346 of the commission of December 1, 2022 establishes the common specification for the groups of devices without intended medical purpose listed in Annex XVI of Regulation (EU) 2017/745 of the European Parliament and of the Council on medical devices.

Favorable opinion emitted by CEIm of the national territory would be only and linked.

Types of medical devices

On clinical researches with medical devices there are different situations listed on the AEMPS website:

1. Medical devices without CE marking (article 62 of the Regulation).
2. Medical devices with CE marking, but not used under authorized and usual conditions of use.

Medical devices with CE marking following their instructions for use and within the intended purpose (Research Project).

Evaluation requirements by the CEIm

1. Clinical research with medical devices without a CE market or with a CE market, but outside the scope of their intended purpose: the following documents must be submitted for initial evaluation or substantial modifications:

• Initial evaluation
• Substantial modification (amendment): the promoter must present the following documents:

1. Presentation letter of the substantial modification.
2. Summary and justification of the changes.
3. Comparative table with previous text versus new text.
4. New version of the documents to be modified with “track changes”
5. New version of the documents to be modified in a fair copy.
6. New documents, if applicable.
7. Documents supporting the changes.
8. Consequences of the modification.
9. Billing details for payment of evaluation fee or fee exemption request.

 

2. Clinical research with medical devices with a CE market following the instructions use and inside the scope of their intended purpose: for the initial evaluation or substantial modifications, the following documents must be presented:

 

• Initial evaluation
• Substantial modification (amendment): the promoter must present the following documents:

1. Presentation letter of the substantial modification.
2. Summary and justification of the changes.
3. Comparative table with previous text versus new text.
4. New version of the documents to be modified with “track changes”
5. New version of the documents to be modified in a fair copy.
6. New documents, if applicable.
7. Documents supporting the changes.
8. Consequences of the modification.
9. Billing details for payment of evaluation fee or fee exemption request.

The management of the contract will be processed in parallel to the application by the CEIm of the Hospital Clínico Universitario de València; and for this purpose, they should contact the Contracts Management Area of the Foundation at the address ensayosclinicos@incliva.es.

 

Documents models

• Patients’ information sheet
• Economic report
• Proceedings and recruitment material

Definition

An observational study with medicines is any research involving the collection of individual data relating to the health of persons, provided that it does not meet any of the conditions required to be considered a clinical trial (established in Article 2.1.i) of Royal Decree 1090/2015 and that it is conducted for any of the following purposes:

• Determine the beneficial effects of medicines, as well as their modifying factors, including the patients’ perspective, and their relationship to the resources used to achieve them.
• Identify, characterize or quantify adverse medicines reactions and other patient safety risks associated with the use of medicines, including potential risk factors or effect modifiers, and measure the effectiveness of risk management measures.
• Obtain information on medicines utilization patterns in the population.
• Observational studies with medicines are intended to complement known medicines information without interfering with routine clinical practice.

The observational studies with medicines are intended to complement the known information on the medicines without interfering with routine clinical practice.

Normative

The Royal Decree 957/2020, November 3, which regulates observational studies with medicinal products for human use, establishes the conditions for the evaluation, conduct and follow-up of observational studies with medicinal products for human use carried out in Spain.

Favorable opinion emitted by CEIm of the national territory would be only and linked.

Evaluation requirements by the CEIm

The instructions of the Spanish Agency of Medicines and Health Products (AEMPS) for conducting observational studies with medicines can be found at the following link: AEMPS. In the case of prospective follow-up observational studies, authorization must be requested from the Autonomous Committee for Prospective Observational Studies of Medicines of the Valencian Community (CAEPO).

For the initial evaluation or substantial modifications, the following documents must be presented:

• Initial evaluation
• Substantial modification (amendment): the promoter must present the following documents:

1. Presentation letter of the substantial modification.
2. Summary and justification of the changes.
3. Comparative table with previous text versus new text.
4. New version of the documents to be modified with “track changes”
5. New version of the documents to be modified in a fair copy.
6. New documents, if applicable.
7. Documents supporting the changes.
8. Consequences of the modification.
9. Billing details for payment of evaluation fee or fee exemption request.

The management of the contract will be processed in parallel to the application by the CEIm of the Hospital Clínico Universitario de València; and for this purpose, they should contact the Contracts Management Area of the Foundation at the address ensayosclinicos@incliva.es.

 Documents models

• Patients’ information sheet
• Economic report

Definition

A research project is any biomedical research involving interventions on human beings, the performance of genetic analyses, the processing of genetic data of a personal nature or of biological samples of human origin.

Normative

According to Law 14/2007, of July 3, 2007, on Biomedical Research, the authorization and development of any research project on human beings or their biological material will require the prior and mandatory favorable report of the Research Ethics Committee. The law is built on the principles of the integrity of persons and the protection of the dignity and identity of the human being in any biomedical research. The same obligation is provided for in the Organic Law 3/2018, of December 5, on the Protection of Personal Data and guarantee of digital rights) and in the Implementing Regulation (EU) 2022/868 of the European Parliament and of the Council of 30 May 2022 on European data governance.

Order SSI/81/2017 of January 19 establishes the basic guidelines for action aimed at guaranteeing the patient’s right to dignity and privacy when attended by professionals undergoing specialized training in Health Sciences (residents in training). The following document contains some points of particular relevance of this Order SSI/81/2017: protocol of confidentiality of academic studies.

Evaluation requirements by the CEIm

For the initial evaluation or substantial modifications, the following documents must be presented:

• Initial evaluation
• Substantial modification (amendment): the following documentation must be submitted at the email ceic_hcv@gva.es

1. A presentation letter that includes the summary and the changes justification.
2. New version of the documents to be modified with “track changes”.
3. New version of the documents to be modified in a fair copy.
4. New documents, if necessary.

Documents models:

• Submission of documentation (“Dossier”)
• Confidentiality agreement for residents
• Confidentiality agreement for students
• Project template
• Patient information sheet
• Informed consent extension request template
• Principal Investigator’s commitment and Service Chief’s authorization
• Principal Investigator’s report
• Approval from involved departments
• Project economic report
• Confidentiality agreement for external researchers of the Regional Ministry for Health of the Valencian Government.

According with the regulations of the University of Valencia, the end-of-degree project (TFG)  in the modality of research work involving patients must have a favorable report from the CEIC or CEIm of the Center where the research is carried out.

If the research topic of the Master’s Thesis (TFM) or Doctoral Thesis is related to animal experimentation, biosafety or human research, even if it is only the use of medical records, biological samples of human origin or biological agents, the evaluation by the CEIC or CEIm of the Center where the research is carried out must be requested prior to its realization (www.uv.es/uvetica).

Normative

Order SSI/81/2017 of January 19 establishes the basic guidelines for action aimed at guaranteeing the patient’s right to dignity and privacy when attended in the presence of students of degrees related to health sciences (students) and when attended by professionals undergoing specialized training in Health Sciences (residents in training). The following document contains some points of particular relevance of this Order SSI/81/2017: protocol of confidentiality of academic studies.

 

Evaluation requirements by the CEIm

For the initial evaluation or substantial modifications, the following documents must be presented:

• Initial evaluation
• Substantial modification (amendment): the following documentation must be submitted at the email ceic_hcv@gva.es

1. A presentation letter that includes the summary and the changes justification.
2. New version of the documents to be modified with “track changes”.
3. New version of the documents to be modified in a fair copy.
4. New documents, if necessary.

Documents models

• Submission of documentation (“Dossier”)
• Confidentiality agreement for residents
• Confidentiality agreement for students
• Project template
• Patient information sheet
• Informed consent extension request template
• Principal Investigator’s commitment and Service Chief’s authorization
• Principal Investigator’s report
• Approval from involved departments
• Project economic report
• Confidentiality agreement for external researchers of the Regional Ministry for Health of the Valencian Government

Normative

According to the latest amendment of September 05, 2022 of Law 14/2007, of July 3, on Biomedical Research, the Research Ethics Committees are responsible for the authorization of research projects with human pluripotent cells obtained by cellular reprogramming when they involve:

1. a) Its generation through the use of non-embryonic somatic cells from healthy or diseased donors and their characterization, including the formation of teratomas.
2. b) Its generation from registered cells, of human origin, non-embryonic, coming from biobanks or of commercial origin.
3. c) Its use or that of its derivatives, coming from biobanks or from researchers in other countries for in vitro research, except those that have reproductive purposes, gamete production and formation of interspecies primary chimeras.

Evaluation requirements by the CEIm

For the initial evaluation or substantial modifications of research projects involving Induced Pluripotent Stem Cells (iPSC) the following documents must be presented:

• Initial evaluation
• Substantial modification (amendment): the following documentation must be submitted at the email (ceic_hcv@gva.es)

1. A presentation letter that includes the summary and the changes justification.
2. New version of the documents to be modified with “track changes”.
3. New version of the documents to be modified in a fair copy.
4. New documents, if necessary.

Documents models

The Institute of Health Carlos III has drafted a document with the indications for the drafting of the Participant Information Sheet and the Informed Consent for research projects involving the generation of iPSCs.

• Patient information sheet

Definición

Los registros médicos o de enfermedades son sistemas estructurados de recopilación, almacenamiento y gestión de datos clínicos y epidemiológicos sobre pacientes afectados por una enfermedad específica, un grupo de enfermedades o una condición de salud. Su propósito principal es servir como herramienta para la vigilancia epidemiológica, la investigación clínica, la evaluación de tratamientos y la planificación de políticas de salud pública. Estos registros contienen información estandarizada, como datos demográficos, diagnósticos, tratamientos, resultados de salud y seguimiento longitudinal de los pacientes.

Para garantizar su calidad, interoperabilidad y comparabilidad internacional, suelen utilizar estándares reconocidos como la Clasificación Internacional de Enfermedades (CIE-10), SNOMED CT y FHIR.

Asimismo, están sujetos a estrictas normativas éticas y legales, como el Reglamento General de Protección de Datos (RGPD) en Europa o la HIPAA en EE. UU., que aseguran la protección y confidencialidad de los datos personales. Los registros pueden ser gestionados por instituciones públicas, privadas o mixtas y requieren procedimientos rigurosos de autorización para el acceso a sus datos, a fin de garantizar un uso legítimo y responsable en investigación biomédica, clínica y de salud poblacional.

Normativa

En España, la operación de los registros médicos o de enfermedades está sujeta a un marco normativo que combina legislación nacional y europea para garantizar la protección de datos personales y el uso ético de la información clínica. A nivel europeo, el Reglamento General de Protección de Datos (RGPD, UE 2016/679) establece los principios fundamentales para el tratamiento de datos personales, desarrollando detalladamente los aplicables a los de categorías especiales, como los datos de salud, exigiendo para su uso, el consentimiento explícito del paciente o su tratamiento por interés público, investigación científica o fines estadísticos. En el ámbito nacional, la Ley Orgánica 3/2018, de Protección de Datos Personales y garantía de los derechos digitales (LOPDGDD) adapta el RGPD al contexto español, especificando las condiciones para el tratamiento de datos de salud y su seudonimización. Además, la Ley 14/2007, de Investigación Biomédica regula el uso de datos en la investigación científica y establece los requisitos para los registros relacionados con ensayos clínicos y estudios observacionales. En el caso de registros de enfermedades específicas, como el cáncer, la Ley 33/2011, General de Salud Pública, y los decretos autonómicos también pueden imponer la obligatoriedad de notificación y registro. Estas normas garantizan la seguridad, confidencialidad e interoperabilidad de los registros, permitiendo su uso responsable en investigación y salud pública.

Requisitos para la evaluación por el CEIm

1. F‐CE‐GEva‐2R Declaración responsable de uso confidencial, cumplimentado y firmado por el personal solicitante y el titular
2. F‐CE‐GEva‐3R Consentimiento informado de tratamiento y cesión de datos a registros, cumplimentado con los datos del registro
3. Documentación de información general sobre el registro, generalmente es elaborada por el titular, sobre:
   • las finalidades y el objetivo general del registro
   • la descripción o listado de las variables que se pretende recoger y la tipología de personas de las que provienen
4. Información sobre el procedimiento o mecanismo para que los investigadores realicen la solicitud de acceso/uso de los datos del registro. La solicitud suele/debería incluir:
   • El protocolo de investigación aprobado por un Comité de Ética para Investigación.
   • Información sobre los responsables del proyecto (institución, equipo de investigación).
   • Justificación del uso de los datos solicitados (criterio de necesidad y proporcionalidad).
   • Declaración de cumplimiento ético y legal.
   • Plan de gestión y protección de la confidencialidad de los datos.
5. Información sobre el procedimiento o mecanismo para la evaluación de las solicitudes de acceso a datos presentadas. De manera general, en un registro la evaluación se realiza y aprueba por distintos órganos colegiados, por ejemplo, los siguientes:
   • Comités de Ética en Investigación (CEI): Para garantizar que el uso de los datos cumple principios éticos (Declaración de Helsinki).
   • Comités Científicos o Técnicos: Para evaluar la calidad y relevancia del proyecto.
   • Organismo Gestor del Registro: Para verificar que el uso de los datos cumple con sus políticas y términos de acceso.
   • Puntos Clave Evaluados:
   • Justificación y relevancia del estudio.
   • Minimización de riesgos para la confidencialidad de los pacientes.
   • Cumplimiento de la normativa de protección de datos (anonimización o pseudonimización).
   • Capacidad técnica y científica del investigador y su equipo.
6. El “modelo de acuerdo de uso de datos” que el registro firma con cada investigador que es autorizado para usar los datos. Este acuerdo suele/debería incluir los siguientes aspectos:
   • Condiciones específicas de acceso y uso de los datos.
   • Limitaciones sobre la reutilización o distribución de los datos.
   • Compromiso de anonimización de resultados y protección de la confidencialidad.
   • Periodo de tiempo autorizado para el uso de los datos.
   • Obligación de devolución o destrucción de los datos tras finalizar el estudio.
7. Descripción de las medidas de seguridad del registro. Dentro de ellas:
   • especificar el lugar donde se almacenarán los datos
   • Indicar las medidas de seguridad técnicas y organizativas existentes, así como cualquier estándar de seguridad que el registro cumpla (ENS, ISO 270001, etc.)
   • la descripción o identificación de personas que tendrán acceso a los datos como parte de la operación y mantenimiento del registro
   • información sobre evaluaciones de impacto a la privacidad o análisis de riesgos realizados

Modelos de documentos

• F‐CE‐GEva‐2R Declaración responsable de uso confidencial
• F‐CE‐GEva‐3R Consentimiento informado de tratamiento y cesión de datos a registros