Topics - Clinical Trials

Clinical Trials

A clinical trial is a research study conducted in human participants to evaluate the safety and efficacy of a medicine expected to improve patients health. Clinical trials can only be started after a compound has survived rigorous pre-clinical development work, which involves laboratory testing (chemical/biological/pharmacological/toxicological). It is only when these tests show favourable and promising results that a company can proceed to assess the medicine in humans.

The impact of clinical trials

The importance of clinical trials

According to the European Medicines Agency (EMA), around 4,000 trials are authorised each year across the EEA and this phenomenal effort, in partnership with other global research partners is transforming the way we care for patients and treat many diseases. Over the last 60 years, life expectancy across the EU has increased by nearly a decade. Since the 1980s, death rates from HIV have fallen by around 80% and since the 1990s, death rates from cancer have fallen by 20% in some countries. Hepatitis C can now, in most cases, be cured, and advances in targeted, precision medicines are transforming the way we will treat patients in the future.

Medicines’ development takes an average of 12 years until approval for use in patients. Clinical research is an essential part of the development process but it is also the lengthiest and most expensive. Clinical Trials represent on average 58,6% of a product total development costs. EFPIA continues to work with stakeholders to further harmonization of Member States’ administrative requirements and procedures for approval of clinical trials. The goal is to ensure Europe remains competitive in attracting investment in clinical trials, increasing the speed, reducing the costs and allowing the European citizens access to the innovative medicines.

The legislative framework for clinical trials

The conduct of clinical trials (CT) in humans in the EU is regulated through Commission Directive 2001/20/EC[1] and reinforced by Directive 2005/28/EC[2], laying down rules on Good Clinical Practice (GCP). Compliance with them ensures the rights, safety, and wellbeing of clinical trial participants, consistent with the principles of the Declaration of Helsinki[3]; and that the clinical trial data are credible. Compliance with Good Manufacturing Practice (GMP)[4] under Commission Directive 2003/94/EC is also required and ensures that the results of clinical trials are unaffected by inadequate safety, quality or efficacy arising from unsatisfactory manufacture. The directives and supplementary guidance must be read in conjunction with relevant national Member State level legislation and guidelines. 

About clinical trials in EU - From Test Tubes to Animals

Drug discovery aims to find potential disease-altering targets, such as a gene or a protein in humans. When a candidate compound is found, its safety needs to be tested for a specific indication or disease condition. This pre-clinical or non-clinical testing phase takes up to four years. Candidate compounds need to be introduced into a living biological system (animal) to see if they function as anticipated. At least two different species of animals have to be used.

About clinical trials in EU - From Animals to Human Phase 1 Trials

If pre-clinical test results support further development, the candidate compound is tested in humans in a phase 1 clinical trial.  All clinical trials, including phase 1 trials must first be registered in European EudraCT database after which the clinical trial application (CTA) is scrutinised by a Competent Health Authority and an Ethics Committee, in each country where the trial is intended to be conducted.

All clinical trials, including phase 1 trials only include participants who give their free, written consent prior to participation, after being informed about the possible harm the trial medicine may cause. This consent may be withdrawn at any time by the participant. 

Phase 1 trials are conducted in a small number (20 to 80) of healthy volunteers and last approximately one year. The aim is to find the lowest dose at which the treatment is effective and the highest dose at which it can be taken without causing harm. The trial also measures the participant’s clinical response to the medicine, e.g. how it absorbs into the blood or the tissue.

About clinical trials in EU - From Healthy Volunteers to Larger Patient Populations

Where the phase 1 trial is successful, the compound is then evaluated in about 100 to 500 patients with the disease, in a phase 2 trial, for its potential efficacy while gathering further safety data. Taking around two years, it helps determine the most effective dosages, the best method of delivery (e.g. tablet form or injection) and begins evaluating the benefits and risks of the medicine.

Phase 3 – which can take over four years and involves several hundreds to many thousands of patients – is used to test the results of earlier phase 2 trials in larger populations and generate robust data about safety, efficacy and the overall benefit-risk relationship of the medicine. The compound at this stage is almost always compared to placebo (non-active substance) if ethical considerations permit, and/or to an “active comparator”. Active comparators are usually the best standard treatment (where this exists) for the investigated disease .The active comparator is used to determine if the new medicine has additional benefit beyond current treatment.

If the phase 2 and 3 trials meet their objectives, and/or the benefit/risk ratio of the medicine is favourable for a specific indication/ disease condition, the CT sponsor, commonly a pharmaceutical company, submits an application containing in depth information on the safety, efficacy and manufacturing (quality) of the medicine to a Competent Health Authority.  A successful application results in a marketing authorisation for the medicine in that specific indication/ disease condition.

Often, phase 4 post-authorisation trials, that include thousands of patients globally and can take over 10 years to finalise, will be conducted to get more detailed information on medicine’s efficacy and safety in even larger patient populations.  It is also more common to use data from disease and product registries to anticipate trends at this stage. 


Designing a Clinical Trial

Transparency & Privacy

The Journey of Clinical Trials


Clinical Trials Regulation 536/2014 

The European Clinical Trials framework will undergo a major change when the Clinical Trials Regulation 536/2014 [5] comes into application towards the end of 2018. The legislation becomes a regulation, rather than a directive, which will ensure key aspects have identical rules throughout the EU.

The main characteristics of the new Regulation are:

  • A streamlined application procedure via a single entry point, the EU portal.
  • A single set of documents to be prepared and submitted for the clinical trial application (CTA).
  • A harmonised procedure for the assessment of applications for clinical trials, which is divided in two parts. Part I is jointly assessed by all Member States concerned, which means the countries where the trial is intended to be conducted. Part II is assessed by each Member State concerned separately.
  • A harmonised procedure for the assessment of clinical trials application.
  • The involvement of the Ethics Committees in the assessment procedure in accordance with the national law of the Member State concerned but within the overall timelines defined by the Regulation.
  • Extension of the tacit agreement principle to the authorisation process which, without compromising safety, will give sponsors increased legal certainty.
  • Streamlined safety reporting procedures which will spare sponsors from submitting broadly identical information separately to various bodies and different Member States.
  • Increased transparency as regards clinical trials and their outcomes.
  • Union controls in Member States and third countries to ensure that clinical trials rules are being properly supervised and enforced.
  • Clinical trials conducted outside the EU, but referred to in a clinical trial application within the EU, will have to comply with regulatory requirements that are at least equivalent to those applicable in the EU.

EFPIA sees the implementation of the Clinical Trials Regulation as an opportunity to demonstrate Europe’s commitment to clinical innovation, scientific collaboration and transparency of clinical trials information.

In order to meet the essential elements for successful implementation of the Regulation and reaching its objectives, EFPIA has identified three key and distinct needs as follows:

  • Deliver flexible, efficient and streamlined execution of the authorization procedure to 
avoid administrative delays.
  • Enable the required collaboration between concerned Member States, as well as 
  • Appropriately manage the transparency of data over the life of the clinical trial.

In collaboration with EFPIA’s national trade association members, we are monitoring the implementation of the Regulation on the national level through our comprehensive National Trade Association Clinical Trials Implementation Monitor survey (CTiMonitor survey).

Sharing clinical trial information

EFPIA and its members believe that sharing clinical trial information is in the best interests of patients, clinicians and medical research. We are committed to working with stakeholders to ensure that clinical trial information is shared responsibly taking in to account patient anonymity, maintaining the integrity of regulatory systems worldwide and continuing to support innovation with appropriate arrangements for commercial-in-confidence information.

Trials conducted in the EU need to be registered with the EudraCT database. Since 2014, a summary of results of phase 2-4 studies that ended must also be submitted within 12 months of their end to the Clinical Trials Register[6], irrespective of the result (and within 6 months for paediatric trials).

The new EU Clinical Trials Regulation requires the submission of summary results and clinical study reports to be made public, based on predefined disclosure rules [7].  A new EU Portal and Database at the European Medicines Agency for publicly-accessible information should be operational by the end of 2018. 

Data from clinical trials can also be obtained for products, which have been approved by the European Medicines Agency (through the centralised approval procedure) through policy 0043 [8] on access to documents and policy 0070 [9] on proactive publication and access to clinical trial data, which applies to products that were approved by the EMA after the beginning of 2015.

Delivering responsible transparency and data sharing is a process of continuous development, including alignment of companies’ policies to a rapidly evolving regulatory environment 

To support the sharing of clinical trial data, EFPIA and its member companies published and implemented the EPFIA/PhRMA principles for responsible sharing of clinical trial data.  Going beyond the legislative requirements, the principles bring new levels of access to clinical trial data.

Case studies

Johnson & Johnson

Principles for Responsible Clinical Trial Data Sharing


Since the publication of the EFPIA/PhRMA principles for responsible sharing of clinical trial data, companies have made great progress in developing processes for clinical trial data access schemes, translating principles into practice. We are now seeing data being shared with researchers through some particularly innovative solutions and processes. You see data sharing case studies below.

Clinical trials are evolving with new approaches, technologies and designs. They remain an essential part of medical research as they aim at providing the community with the latest innovative treatments and state-of-the-art clinical practice. In the future, clinical trial data will be enhanced by the availability of real world data from patient registries, hospitals and general practitioners. Industry is working with stakeholders to develop systems to maximise the potential of big data while protecting confidentiality of patient data, to further biomedical research.  

[2] COMMISSION DIRECTIVE 2005/28/EC of 8 April 2005
[3] News version of Declaration of Helsinki
[4] The Rules Governing Medicinal Products in the European Union Volume 4, EU Guidelines to Good Manufacturing Practice Medicinal Products for Human and Veterinary Use Annex 13 Investigational Medicinal Products,
[6] Clinical Trials Register,
[7] Appendix to Functional Specifications of EU CT portal and database,
[8] European Medicines Agency policy on access to documents (related to medicinal products for human and veterinary use) Policy 0043,
[9] European Medicines Agency policy on publication of clinical data for medicinal products for human use