GCP – Good Clinical Practice

Version 2, 14.11.2025

Training requirements for the new version of Good Clinical Practice (ICH E6 R3)

The EMA-approved version of ICH E6 R3 was published on January 23, 2025, and came into effect on July 23, 2025. Responsible parties (sponsors and investigators) must identify new and updated training requirements for new or ongoing clinical drug trials.

Training from the Investigator's perspective

According to ICH E6 R3:

The investigator should be qualified by education, training and experience to assume responsibility for the proper conduct of the trial (Annex 1, 2.1.1). The investigator must be able to provide evidence of his/her qualifications and be familiar with the proper use of the investigational product as described in the information sources provided by the sponsor (Annex 1, 2.1.2). The investigator must also have sufficient time, qualified staff, and suitable facilities for the duration of the trial to ensure it is conducted properly and safely (Annex 1, 2.2.2). If the investigator delegates trial-related tasks to others, he/she must ensure that these individuals have sufficient knowledge of the trial protocol, investigational product, and their assigned trial tasks. The training of individuals performing trial-related tasks must correspond to the requirements of their delegated tasks, especially when the tasks exceed their usual training and experience: "Trial-related training to persons assisting in the trial should correspond to what is necessary to enable them to fulfill their delegated trial activities that go beyond their usual training and experience" (Annex 1, 2.3.2).

This highlighted sentence is important: E6 R3 emphasizes trial tasks that exceed individuals' usual training and experience. Not all staff necessarily need ICH E6 training (or retraining); it depends on their role in the trial. For example, a laboratory technician who routinely takes blood samples needs very little training, but the lead investigator must be thoroughly familiar with the guideline. Assistant investigators must be trained in their specific trial tasks, such as the consent process and adverse event reporting. When a new individual or entity is assigned trial-related tasks, it is important to consider their current level of experience in relation to these trial tasks.

The same applies to retraining. When determining the general need for retraining, it is important to consider whether conducting clinical drug trials is routine for the individual or entity (e.g., often in oncology and hematology departments) or if the individual or party only occasionally participates in clinical trials in human medicines. In the latter case, training for a specific trial is more appropriate. Retraining should be considered whenever there are significant updates to trial guidelines, such as the publication of the new E6 R3 version.

Especially regarding ICH E6, Fimea expects lead investigators to familiarize themselves with/train in its R3 version, as they are one of the two legally responsible parties for the trial (along with the sponsor). Individuals or parties to whom the investigator has delegated trial-related tasks need retraining depending on their tasks. If an individual performs tasks for which the guidelines have not changed, retraining is not necessary. However, it is likely that most clinical trial staff will need some retraining due to significant changes in the guidelines. If the trial protocol and other trial manuals already comprehensively describe the tasks of delegated individuals or parties, the need for retraining may be less.

The appropriate amount, frequency, and methods of training are case-specific. Responsible parties (investigator and sponsor) must ensure that training and qualifications are sufficient for the tasks. Since trials vary, there is no one-size-fits-all solution.

Since the sponsor is responsible for selecting the investigator/organization (Annex 1, 3.7.1), the sponsor has a shared responsibility to ensure that each investigator is qualified based on training, orientation, and experience.

Training from the Sponsor's perspective

According to ICH E6 R3:

The sponsor must utilize appropriately qualified individuals and service providers (e.g., biostatisticians, clinical pharmacologists, physicians, data analysts/data managers, auditors, and monitors) throughout the trial (Annex 1, 3.4, 3.11.2.1.(b), 3.11.4.2 (a), 3.16.1 (x) (ii), 4.3.2 and Appendix C.3.1.(l and m)).

When the sponsor uses service providers, it is their responsibility to assess the suitability of the service provider. The sponsor must ensure that the selected service provider can properly perform the tasks assigned to them (Annex 1, 3.6.7). Therefore, the sponsor must assess whether the service provider's staff training is sufficient.

The same training principles apply to sponsors as described in the previous section for investigators.

ICH E6 R3 training

Responsible parties should compare guideline versions using methods such as gap analysis or other means to identify new or updated training requirements for new or ongoing clinical trials.

GCP inspectors may request this comparison or equivalent documentation during GCP inspections and use it to assess whether the ICH E6 R3 training requirements have been properly implemented.

ICH has prepared training package, which can be found in the ICH Training Library (Efficacy Guidelines → E6(R3) – Training Materials). It is important to note that records demonstrating that the investigator and delegated personnel are qualified for their tasks based on training, orientation, and experience are essential records.

Monitoring is a ICH GCP requirement in all clinical trials with medicinal products, as it is one of the principal methods to control trial quality and reliability of trial results (ICH-GCP(R3) principles 6 and 9, CTR 536/2014 article 48). The sponsor is responsible for arranging monitoring. Based on risk assessment, the sponsor must determine the extent and nature of monitoring, taking into account the specific characteristics of the trial and the critical factors affecting quality. Aim and basis of monitoring are described in ICH GCP(R3) Annex 1 section 3.11.4. Monitoring can target a specific investigator site, but it can also be done in a centralised manner. Monitoring can be done on-site or remotely depending on the systems employed in the trial. It should be performed by persons not involved in the clinical conduct of the trial at the site being monitored (Annex 1 3.11.4). A description of monitoring should be presented in the trial protocol (ICH-GCP(R3) Appendix B.12.2 and CTR 536/2014 Annex 1 D. 17. (ad)) and/or in a separate monitoring plan (ICH-GCP(R3) 3.11.4.3).

Version 1, 14.11.2025

Laadun suunnittelu (Quality by Design, QbD) ja kriittiset laatutekijät (Critical to Quality Factors)
Kliinisen lääketutkimuksen laatu on tarkoitukseen soveltuvuutta (Fitness for Purpose). Laatu varmistetaan suunnittelemalla laatu proaktiivisesti osaksi tutkimussuunnitelmaa ja -prosesseja. Laadun suunnittelua pitää toteuttaa ennen tutkimuksen aloittamista ja sen aikana.
Laadun suunnittelu keskittyy tutkimuksen kannalta kriittisiin laatutekijöihin (Critical to Quality Factors) ja niihin liittyviin riskeihin, jotta tutkimuksen tavoitteet toteutuisivat mahdollisimman suurella todennäköisyydellä samalla kun suojellaan tutkimukseen osallistujia ja varmistetaan tulosten luotettavuus. Tutkimuksen osallistujien suojelulla tarkoitetaan osallistujien oikeuksien, turvallisuuden ja hyvinvoinnin suojelua.
Laatutekijät ovat kriittisiä, jos niiden puutteellinen suunnittelu tai toteutus voi vaarantaa tutkimuksen tulosten luotettavuuden ja/tai osallistujien turvallisuuden tai oikeudet. Kriittiset laatutekijät ovat tutkimuskohtaisia. Ne pitää määrittää ennen tutkimuksen aloittamista. Määrittämisessä auttaa ICH E8 (R1) General considerations for clinical studies -ohje. 
Esimerkiksi jos tutkimuksen päämuuttujan tietoja kerätään sähköisellä potilaspäiväkirjalla, se on kriittinen laatutekijä. Tämän takia on tarkoituksenmukaista kohdistaa sähköisen potilaspäiväkirjan hallintaan ja laadunvarmistukseen riittävästi huomiota sekä suunnitteluvaiheessa että tutkimuksen toteutuksen aikana.
Laadun suunnittelussa auttaa myös potilaiden (ja muiden oleellisten sidosryhmien) osallistaminen. Esimerkiksi Rationaalisen lääkehoidon tutkimusverkoston (RATTI) kautta löytyy potilaan osallistumisen tarkastuslista tutkijalle, mitä voi soveltaa myös kliinisissä interventiotutkimuksissa.

Suhteellinen riskiperusteinen lähestymistapa (proportionate risk-based approach)
Kliinisen tutkimuksen toteuttamista tukevien prosessien tulisi olla suhteessa kerättävän tiedon merkitykseen, osallistujien turvallisuuteen ja tutkimustulosten luotettavuuteen. 
Suhteellista riskiperusteista lähestymistapaa voi toteuttaa esimerkiksi riskien hallinnassa, tietokoneistettujen järjestelmien hallinnassa, tutkimustehtävien delegoinnissa, tutkimuksen monitoroinnissa ja olennaisten tallenteiden määrittämisessä.
Esimerkiksi osallistujan painon punnitseminen voi olla osa henkilökunnan normaalia työtä, jolloin tehtävää ei tarvitse erikseen delegoida tai kouluttaa. Myös laadunvarmistuksen, valvonnan ja riskienhallinnan tarve voi olla silloin vähäisempi. Sen sijaan, jos kyseessä on esimerkiksi vastasyntyneen paino, jota käytetään tutkimusvalmisteen annoksen määrittämiseen, tehtävään liittyy suurempi riski. Tällöin tarvitaan huolellinen riskienhallinta, valvonta, laadunvarmistus sekä tehtävän selkeä delegointi ja koulutus.

Tarkoituksenmukaisuus (fitness for purpose)
Tutkimus, sen prosessit ja tiedot/tulokset ovat tarkoituksenmukaisia, jos ne ovat riittäviä ja sopivia käyttötarkoitukseensa. Tarkoituksenmukaisuus riippuu asiayhteydestä (mm. laatu, tietokoneistetut järjestelmät, toimeksiantajan/tutkijan valvonta).
Esimerkiksi tutkimuksessa kerättyjen tietojen ei tarvitse olla täysin virheettömiä, mutta niiden on oltava riittävän virheettömiä, jotta tutkimuksesta voidaan tehdä luotettavia ja oikeita johtopäätöksiä. Tarkoituksenmukaisuutta on myös se, että käytetään tietokoneistettuja järjestelmiä, jos ne vähentävät virheitä ja helpottavat tiedonhallintaa, mutta ei käytetä liian monimutkaisia järjestelmiä, jos yksinkertaisempikin riittää. Myös tilastolliseen voimalaskentaan perustuva otoskoko on osa tarkoituksenmukaista tutkimuksen suunnittelua. Sen avulla varmistetaan, että otos on riittävän suuri luotettavien tulosten saamiseksi, mutta ei tarpeettoman suuri, jolloin osallistujia kuormitetaan turhaan ja resursseja käytetään tehottomasti.

Metatieto (metadata) ja kirjausketju (audit trail)
Metatieto tarkoittaa tietoa tiedosta. Se on kuvailevaa tai jäsentävää tietoa, joka kertoo jonkin aineiston sisällöstä, rakenteesta, kontekstista tai ominaisuuksista. Metatieto ei ole itse sisältöä, vaan se auttaa ymmärtämään, hallitsemaan ja hyödyntämään sisältöä. Metatietoa on esimerkiksi tiedoston nimi, sijaintitiedot, yhteydet muihin tiedostoihin, koko, muoto ja sisällön määritteet.
Metatieto sisältää myös kirjausketjun eli tutummin audit trailin. Audit trail tarkoittaa jäljitettävyyttä varmistavaa tietoa, joka tallentaa kaikki merkittävät tapahtumat, muutokset ja käyttäjätoiminnot. Se kertoo, kuka teki mitä, milloin ja miksi.
 

Version 1, 30.1.2026

The requirement that the monitors, auditors and inspectors must have direct access to medical records appears in several sections of ICH E6(R3), both a requirement for investigator (Annex 1 2.8.10, 2.12.14) and sponsor (Annex 1 3.6.3, 3.16.4, Appendix B.11).

The requirement for direct access is also described in the EU regulation 536/2014 on clinical trials on medicinal products for human use. The regulation states that the protocol must include a statement from the sponsor (either in the protocol or in a separate document) confirming that the investigators and institutions involved in the clinical trial are to permit clinical trial-related monitoring, audits and regulatory inspections, including provision of direct access to source data and documents.
According to the Guideline on computerised systems and electronic data in clinical trials, section A6.8 Direct access, the access should be direct, read-only access, which is restricted to all relevant data for all trial participants (including potential participants screened but not enrolled in the trial) and should include access to audit trails.

Responsible investigator and data controller must plan how the direct access for monitors, auditors, and inspectors to electronic client/patient records will be arranged. Where existing electronic health/medical systems do not yet support this functionality, the need for such access should be considered and addressed as part of the next feasible system update (or if new system is purchased).

If the electronic health/medical record system does not currently provide the required technical capability for direct access, relying solely on printed records does not necessarily fulfill the direct access requirement and does not always provide a sufficient quality control method for clinical trial purposes. There are several reasons for this which have been seen during the inspections. All the relevant information is not always captured in the printouts, because it may, for example, be stored in different locations within the system. This can result in incomplete medical histories or missing safety information. In addition, updates made in the electronic source data after the printing are not reflected in the printouts (and vice versa), or the changes made are not clearly visible. Printouts can also be misplaced, which, in the worst case, may lead to data breaches or rejection of clinical trial data.

If it is not currently possible to provide direct access, the clinical trial site should manage the limitation in the organisation’s (or electronic system’s) risk assessment, and clinical trial site should implement appropriate interim measures until system updates can be made (or a new system is purchased). Organisations’ internal Data Protection Officers help to ensure compliance with data protection regulations. Chapter 2 of the Act 703/2023 on the Social and Health Care data contains general principles on the processing of client data. If supported access, i.e. so called over-the-shoulder access is used, appropriate and acceptable measures must be in place, both from the clinical trial and organizational perspectives, for example to ensure appropriate traceability. This includes, for example, keeping records of persons who viewed the medical data, when the access occurred, how the records were accessed, and what information was viewed, and how and where the access information is stored.