Since May 1, 2004, Royal Decree 223/2004 has replaced Royal Decree 561/1993 , of April 16, which established the requirements for the conduct of clinical trials with medicinal products, although the latter is still applicable to clinical trials processed while it was in force.

• Declaration ofHelsinki
• Oviedo Convention ,of April 4, 1997 on human rights and biomedicine, ratified in the BOE of October, 1999.
• Legislation for the protection of personal data, according to Organic Law 15/1999 on the Protection of Personal Data.
• Rights and duties related to clinical information and documentation, according to Law 41/2002, of November 14, regulating the autonomy of patients

Also applicable to all clinical trials, together with Good Clinical Practice (GCP) Standards is the planning, conduct and communication of all the clinical trials conducted in Spain, and the set of ethical and scientific requirements acknowledged on an international scale and to guarantee the protection of the rights, safety and welfare of all trial subjects and the reliability of trial results.
On a European level, European Parliament and Council Directive 2001/20/EC, of April 4, 2001, regulates the approximation of the legal, regulatory and administrative provisions of member States on the application of good clinical practice in the conduct of clinical trials of medicinal products for human use.


Spanish legislation regulating other types of research in humans

Chapter V of Royal Decree 711/2002, of July 19, 2002, regulating the pharmacovigilance of medicinal products for human use establishes the rules for the conduct of studies with medicinal products in usual conditions of use, called post-authorisation observational studies.

At the same time, the Committee for the Safety of Medicinal Products for Human Use developed specific guidelines for this type of study, defined in annex IV to Circular Nº 15/2002, of September 30, 2002. Reporting procedures in pharmacovigilance matters for medicinal products for human use between the pharmaceutical Industry and the Spanish Pharmacovigilance System of medicinal products for human use,published by the Spanish Agency for Medicines and Medical Devices. The conduct of this type of study must consider, besides State legislation, the legislation established by the Autonomous Regions where post-authorisation observational studies are conducted. This regional legislation is currently at different stages of development, and must therefore be consulted locally before conducting a study of this kind.

Circular 7/2004 on clinical research with medical devices defines the standards for research with medical devices, according to European directive 2001/20/EC and Spanish legislation RD 223/2004.

International Conference on Harmonisation (ICH) guidelines

The International Conference on Harmonisation (International Conference on Harmonisation of technical requirements for registration of pharmaceuticals for human use or ICH) arose in 1990 as a joint initiative of the regulatory authorities and the pharmaceutical industry, aimed at establishing the same minimal technical and procedural requirements for the three main pharmaceutical markets (United States, Europe and Japan), so the regulatory requirements for the authorisation of new pharmaceutical products are similar in the three places and to prevent repeating similar studies to satisfy the different demands in each area.

Based on this initiative, a series of guidelines have been developed in 4 areas (quality, safety, efficacy and multidisciplinary (referring to regulatory procedures)) establishing the methods approved in the three markets for a series of processes and procedures. Although they are not compulsory, they constitute an excellent point of reference.

The efficacy guidelines identify the best methods for different aspects of clinical research, based on ethical and technical criteria, aimed at drug registration. The website of the European Agency for the Evaluation of Medicinal Products (EMEA) includes all these guidelines as documents accepted for application in the European Union:

Topic E1A Step 5 Note for Guidance on Population Exposure: The extent of Population Exposure to assess Clinical Safety (CPMP/ICH/375/95 adopted November 94)
Topic E2A Step 5 Note for Guidance on Good Clinical Safety Data Management: Definitions and Standards for Expedited Reporting (CPMP/ICH/377/95 - adopted November 94)
Topic E 2B(M) Step 5 Modification Note for Guidance on Clinical Safety Data Management: Data Elements for Transmission of Individual Case Safety Reports (ICH ICSR DTD Version 2.3)(CPMP/ICH/287/95 - Mod. released for information November 2000)
Topic E2B (M) Step 5 Clinical Safety Data Management: Data Elements for Transmission of Individual Case Safety Reports- Release for information November 2003
Topic E2C Step 4 Note for Guidance on Clinical Safety Data Management: Periodic Safety Update Reports for Marketed Drugs (CPMP/ICH/288/95 - adopted December 96)
Topic V1* Clinical Safety Data Management Periodic Safety Update Reports for Marketed Drugs (CPMP/ICH/4679/02 - final approval of addendum by CPMP February 2003) (Addendum to ICH E2C )
Topic E2D Note for Guidance on Definition and Standards for Expedited Reporting (CPMP/ICH/3945/03 -Final approval by CPMP November 2003)
Topic E3 Step 4 Note for Guidance on Structure and Content of Clinical Study Reports(CPMP/ICH/137/95 - adopted Dec. 95). Annex I ; Annex II ; Annex III ; Annex IVa ; Annex IVb ; Annex V ; Annex VI ; Annex VII ; Annex VIII
Topic E4 Step 5 Note for Guidance on Dose Response Information to support Drug Registration (CPMP/ICH/378/95 - adopted May 94)
Topic E5 Step 4 Note for Guidance on Ethnic Factors in the Acceptability of Foreign Clinical Data.(CPMP/ICH/289/95 - adopted Mar.98)
Topic E5 Step 5 Questions and Answers Ethnic Factors in the Acceptability of Foreign Clinical Data (CPMP/ICH/289/95) - Release for information November 2003
Topic E6 Step 5 Note for Guidance on Good Clinical Practice(CPMP/ICH/135/95 - adopted July 96)
Explanatory Note and Comments to CPMP/ICH/135/95
Topic E7 Step 5 Note for Guidance on Studies in support of Special Populations: Geriatrics( CPMP/ICH/379/95 - adopted Sept. 93)
Topic E8 Step 4 Note for Guidance on General Considerations for Clinical Trials(CPMP/ICH/291/95 - adopted Sept. 97)
Topic E9 Step 4 Note for Guidance on Statistical Principles for Clinical Trials.(CPMP/ICH/363/96 - adopted Mar.98)
Topic E10 Step 4 Note for Guidance on Choice of Control Group for Clinical Trials (CPMP/ICH/364/96 - adopted July 2000)
Topic E11 Step 4 Note for Guidance on Clinical Investigation of Medicinal Products in the Paediatric Population.(CPMP/ICH/2711/99 - adopted July 2000)


Other links of interest  

Spanish Agency for Medicines and Medical Devices
Ministry of Health and Consumer Affairs
European Agency for the Evaluation of Medicinal Products.
F DA-CDER Food and Drug Administration, Center for Drug Evaluation and Research