Key principles for planning and conducting clinical trials: the European Medicines Agency's vision for 2030

Introduction

In modern healthcare, clinical trials are one of the key tools for the development of medical science and clinical practice. Every year, clinicians and researchers face a constantly growing flow of scientific information, which increases the requirements for critical appraisal of the quality and reliability of the obtained data.

This article is based on a fundamental study by a group of authors on the prospects for the development of the clinical evidence base up to 2030, and presents an analysis of six core principles [1]. That work provides a comprehensive overview of current trends and a forecast for the development of the clinical evidence base up to 2030, including an analysis of methodological challenges, technological innovations, and regulatory changes.

The quality of clinical research becomes particularly important in the context of the rapid development of the pharmaceutical industry and the need for prompt implementation of new treatment methods. At the same time, a fundamental contradiction arises: on the one hand, accelerated development and introduction of innovative drugs are required; on the other hand, a high level of evidence and safety of new therapeutic approaches must be ensured.

The methodology of clinical research must comply with strict international standards, ensure the validity and reproducibility of results, and take into account the interests of all participants in the process. Under these conditions, the formulation and implementation of clear principles for conducting clinical trials, allowing a balance between the speed of data acquisition and their quality, become particularly relevant.

Modern healthcare is characterised by high dynamics of development, active introduction of new technologies and research methods. This requires continuous improvement of approaches to the organisation and conduct of clinical trials, the development of modern methodological solutions, and the standardisation of research processes.

The relevance of the topic is determined by the need to form an effective clinical research system capable of ensuring:

• high speed of obtaining results;

• reliability of collected data;

• safety of research participants;

• compliance with international standards;

• optimal cost‑benefit ratio.

This article examines six fundamental principles for conducting clinical trials, formulated in the EMA document “Vision of the European regulatory network for medicines in the field of clinical evidence by 2030” and forming the foundation of modern methodology:

1. Patient‑centred orientation of clinical research.

2. Use of existing data to identify knowledge gaps.

3. Clarity in formulating research questions.

4. Coverage of available data spectra with selection of the most effective and rapid methods.

5. Early agreement on methods for obtaining clinical data with all stakeholders.

6. Transparency and openness of clinical trials.

The practical significance of the work lies in systematising the basic principles of clinical research, which can serve as a methodological basis for planning and conducting projects of various levels of complexity in modern medical practice.

Principle 1: Orientation of clinical research to patient needs

Decision No. 79 of the EEC Council of November 3, 2016 “On approval of the Rules of Good Clinical Practice of the Eurasian Economic Union” regulates the protection of patient rights and compliance with ethical standards in clinical trials [2]. At the same time, the patient in the context of clinical trials is often viewed primarily as an object of research rather than an active participant.

Most often, drug development is aimed at eliminating the aetiology of the disease, but achieving this goal may take decades. Much less frequently, clinical trials focus on alleviating symptoms and improving quality of life.

A notable example is dornase alfa, a human recombinant deoxyribonuclease 1. Dornase alfa is one of the main drugs for the treatment of cystic fibrosis, with high efficacy and a solid evidence base. However, its use may be accompanied by voice changes in the patient [3]. This effect can cause social and psychological discomfort, leading to reduced treatment adherence.

Patient comfort and subjective well‑being are often no less important to them than, for example, survival rates. Attentiveness to the patient's opinion makes the clinical trial less traumatic and more focused on achieving their physiological and psychological well‑being.

Patient‑centred orientation in clinical research allows:

• increasing the patient's sense of safety and trust;

• enhancing adherence to prescribed therapy;

• increasing patient involvement in the research process;

• making clinical data collection more accurate and transparent.

Thus, consideration of patient priorities and experience becomes a necessary condition for high‑quality planning and conduct of clinical trials.

Principle 2: Use existing data to identify and address gaps

Specialists in many areas of healthcare face the problem of insufficient continuity of information. Often, a patient arrives without accompanying medical records, and their treatment essentially starts from a “blank slate,” leading to a loss of precious time.

The situation with clinical trials is largely similar. Drug development projects may not rely sufficiently on the results of previous studies. Pharmaceutical companies' databases are fragmented and, as a rule, not integrated with each other due to competitive restrictions. Around the world, active development of new metadata and specialised repositories is underway, indicating a pronounced need for such infrastructure projects in healthcare [4].

Another important factor is that the vast majority of published studies have positive results. The work by Showell MG et al. “Time to publication for results of clinical trials” demonstrates a pronounced publication bias [5]. The authors systematised data on the publication activity of clinical trials and identified significant patterns related to the nature of results, study size, funding source, and a number of other factors.

The development of drugs that have not shown the expected efficacy is often delayed for years or completely discontinued without proper reflection in the publication field. Trials with positive results were published on average after 2 years, while studies with negative or neutral results — after approximately 2.6 years. This facilitates faster dissemination of data on potentially effective interventions but simultaneously slows access to information about ineffective or potentially dangerous methods. Clinical trials with positive results (statistically significant in favour of the experimental intervention) were published significantly more often than studies with negative or neutral outcomes; the probability of publication was more than two and a half times higher.

As a result, the scientific community loses the opportunity to fully assess adverse outcomes, leading to repetition of ineffective studies and suboptimal use of resources. Patients are deprived of earlier access to next‑generation drugs, and pharmaceutical companies lose time and motivation to continue developing such molecules. Systematic use of already accumulated data and results of both successful and unsuccessful trials can reduce duplication, optimise the design of new projects, and accelerate the development of pharmacotherapy.

Principle 3: Clarity in the formulation of research questions

One of the most important stages of a clinical trial is formulating questions aimed at filling the existing “gap” in the studied area. In the structure of a clinical trial, the stage of formulating research questions occupies a special place: it sets the framework for the entire work and determines how effectively the identified “gap” in knowledge can be filled.

The essence of the problem is that medical science regularly faces data fragmentation: the results of individual studies often contradict each other or do not allow forming a holistic view of the problem. Under such conditions, an inaccurately formulated research question leads to vagueness of methodology, complicates the search for relevant sources, and reduces the practical value of the obtained conclusions.

Thus, clarity in formulating research questions is not a formal step but a fundamental principle that determines the quality of a clinical trial. A correctly formulated question ensures:

• purposefulness and focus of scientific search;

• methodological rigor and validity of the study design;

• increased reliability and reproducibility of results;

• practical significance of conclusions for clinical practice.

The use of structured frameworks, such as PICO, facilitates standardisation of question formulation and eases further literature analysis and study planning. The PICO framework (Population, Intervention, Comparison, Outcome) was proposed by Richardson et al. in 1995 as a tool for formulating focused clinical questions and planning studies within evidence‑based medicine [20].

Principle 4: Covering the spectrum of data and methods with selection of the highest quality and fastest methods

The fourth principle emphasises the need to find ways to accelerate clinical trials while maintaining high quality of the obtained data. Randomised controlled trials (RCTs) remain the gold standard for assessing the efficacy and safety of medical interventions. Over time, requirements for reporting RCT results have been standardised using the CONSORT (Consolidated Standards of Reporting Trials) system, reflecting the drive to optimise reporting quality and increase research transparency.

Currently, artificial intelligence (AI) plays one of the most prominent roles in optimising clinical trials, with companies around the world investing significant resources in its development. A notable example is the high efficiency of machine learning algorithms for identifying patients at elevated risk of Fabry disease.

In the Russian Federation, initiatives aimed at accelerating clinical trials are already being implemented. This is partly due to the tasks of active import substitution of drugs and medical technologies. Particular attention deserves efforts to accelerate and standardise the assessment of drug costs. In particular, approaches to optimising pharmacoeconomic analysis of biosimilars are being actively developed, which can reduce the cost of the final product and increase its accessibility for patients.

A rational combination of RCT data, real‑world data sources, and modern analytical tools allows simultaneously increasing the informativeness of studies and reducing time and resource costs.

Principle 5: Agree in advance on methods for obtaining clinical data with all stakeholders

The need to implement this principle is reflected in the activities of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH).

The fundamental significance of this principle is that it ensures coordinated interaction of all participants already at the study planning stage. This is critically important because modern clinical trials often involve multiple stakeholders, each of which may use its own methodological approaches and technical solutions.

One of the key problems of interdepartmental and cross‑border coordination is the heterogeneity of formats and structure of data sources. Metadata may differ both in file types and in the ways of centralisation in local systems, which often precludes the very possibility of their effective exchange and shared use. This creates serious obstacles for effective information exchange and its joint use within a single study. Standardisation of processes is needed, covering all aspects of data work — from initial collection to final processing and analysis. Particular attention should be paid to the development of unified information exchange protocols and the introduction of modern data processing tools.

The technological aspect of implementing this principle may include not only the development of standards but also the creation of platforms for information exchange, implementation of data protection systems, ensuring their integrity and confidentiality.

The ultimate goal of this principle is to form an effective and sustainable model of clinical trials, where all participants in the process work according to unified methodological principles. This allows minimising technical barriers, accelerating the research process, and ensuring high quality of the obtained results.

Principle 6: Transparency is the foundation of public trust

This principle is the most comprehensive and fundamental, although it is presented last in the structure of this article. Only with a high level of trust from all parties, with honesty and openness of clinical trials, can the full implementation of the previous five principles be achieved.

The essence of the transparency principle is that all research results should be accessible for analysis and verification regardless of their nature. This means the inadmissibility of concealing or distorting information about the conduct of the study and its results. Honest presentation of data ensures the possibility of independent assessment of the quality and reliability of the obtained results.

In practical implementation, the transparency principle requires a detailed description of all stages of the study.

Conclusion

Consistent application of the six principles discussed contributes to improving the quality, efficiency, and reproducibility of clinical trials, as well as strengthening trust in their results from the scientific community, regulators, and patients.