SUMMARY CLINICAL STUDIES
Inhoudsopgave
1 Protocol in a clinical trial ....................................................................................................... 3
1.1 Start-up of a clinical trial: Essential documents ...................................................................... 3
1.2 What Is a Protocol? ............................................................................................................... 3
1.3 Structured overview of protocol ............................................................................................. 4
1.4 Protocol content ................................................................................................................... 7
2 Legal framework for clinical research on humans in Belgium ................................................. 19
2.1 Old Legal framework ........................................................................................................... 19
2.2 “Old” Legal framework for clinical research in Belgium ......................................................... 20
2.3 “New” legal framework ....................................................................................................... 21
2.4 Why a New Legal Framework for Clinical Trials in the EU? ..................................................... 22
2.5 Why a New Legal Framework for Clinical Investigations (Medical Devices)? ........................... 24
2.6 Definitions .......................................................................................................................... 25
2.7 Scope ................................................................................................................................. 26
2.8 Actors Involved in Clinical Studies ....................................................................................... 28
2.8.1 Who Can Be the Principal Investigator (PI)? ...................................................................... 30
2.8.2 Sponsor .......................................................................................................................... 31
2.8.3 Non-Commercial Clinical Studies .................................................................................... 32
2.8.4 Accredited bodies ........................................................................................................... 33
2.8.5 Co-sponsorship .............................................................................................................. 33
2.8.6 CRO ............................................................................................................................... 34
2.9 Authorization procedure ...................................................................................................... 34
2.9.1 Remaining experiments ................................................................................................... 35
2.9.2 Clinical trials ................................................................................................................... 37
Europe: ..................................................................................................................................... 39
Belgium: .................................................................................................................................... 43
2.10 Transition period ................................................................................................................. 46
2.11 Vulnerable populations ....................................................................................................... 47
2.12 Liability and insurance......................................................................................................... 48
2.13 Summary ............................................................................................................................ 49
Summary Clinical studies 1
, 2.14 Conclusion ......................................................................................................................... 50
3 Clinical Trial Management Statistics .................................................................................... 50
3.1 General Statistical ideas...................................................................................................... 50
3.2 what endpoint? ................................................................................................................... 52
3.3 Fixed and Adaptive randomization schemes ......................................................................... 52
3.4 Representation of data ........................................................................................................ 53
3.5 Confidence Intervals for a mean (x̄) ...................................................................................... 53
3.6 Enrichment ......................................................................................................................... 58
3.7 Practical enrichment ........................................................................................................... 58
3.8 Prognostic enrichment ........................................................................................................ 58
3.9 Predective enrichment ........................................................................................................ 59
3.10 multiple testing ................................................................................................................... 60
3.11 confidence intervals give: .................................................................................................... 63
4 Study design ........................................................................................................................ 65
4.1 protocol writing ................................................................................................................... 65
4.2 Depression ......................................................................................................................... 65
4.3 Schizofrenie........................................................................................................................ 66
4.4 lipids .................................................................................................................................. 66
4.5 Vaccins .............................................................................................................................. 67
4.6 orphan diseases ................................................................................................................. 67
4.7 diabetes ............................................................................................................................. 68
4.8 cancer ................................................................................................................................ 69
5 informed Consent form (ICF) ................................................................................................ 69
5.1 informed consent process ................................................................................................... 69
5.2 informed consent form ........................................................................................................ 69
5.3 Content and recommendations * ......................................................................................... 70
5.3.1 Cover sheat .................................................................................................................... 70
5.3.2 Description of study and law participation ........................................................................ 71
5.3.3 informed consent ............................................................................................................ 72
Summary Clinical studies 2
,1 PROTOCOL IN A CLINICAL TRIAL
1.1 START-UP OF A CLINICAL TRIAL: ESSENTIAL DOCUMENTS
Starting a clinical trial requires several key documents and the completion of specific
procedures. More detailed information can be found on the UZ Leuven intranet under the
Clinical Trial Center (CTC), and on the official websites of the Ethics Committee (EC) and the
Federal Agency for Medicines and Health Products (FAMHP). Additionally, the CONSORT
guidelines (Consolidated Standards of Reporting Trials) are an important resource for the
proper reporting of clinical trials.
Commercial vs. Non-commercial Studies
A distinction is made between commercial and non-commercial clinical trials:
- Commercial trials are conducted on behalf of a sponsor, often a pharmaceutical
company.
- Non-commercial trials are initiated and conducted by a physician or researcher
without a commercial sponsor.
The classification also depends on the type of study — e.g., retrospective, observational, or
interventional.
Essential Documents for Trial Start-up
The following documents are crucial when starting a clinical trial:
- Protocol
- Informed Consent Form (ICF)
- Participant documents (questionnaire, diary,…)
- Recruitment materials
- Insurance
- Contracts with other departments/hospitals/companies/… (data property, publication
rights,…)
1.2 WHAT IS A PROTOCOL?
A clinical trial protocol is the foundational document that outlines how a clinical trial will be
conducted, how participant safety will be safeguarded, and how the integrity of collected data
will be maintained throughout the study. It serves as a comprehensive plan and must be strictly
followed once the trial begins.
Summary Clinical studies 3
, Purpose of a Protocol
The protocol demonstrates that the researchers have a thorough understanding of the study
they are conducting. It answers key questions such as:
- How will the trial be carried out?
- What safety measures are in place to protect participants?
- How will data be managed, analyzed, and kept reliable?
This document is often the first assignment in the development phase of a clinical trial and is
crucial for ethics approval and regulatory submission.
Core Components of a Protocol
A well-designed protocol contains the following elements:
- General information: Identification of the trial (title, ID), sponsor, investigators,
institutions involved, and responsible parties.
- Background and rationale: The scientific justification for the study. This includes a
summary of relevant preclinical data and prior clinical studies. It explains how dose
levels were determined and why the trial is necessary.
- Study objectives and design: A clear description of the trial’s goals and methodology.
This includes the choice of design (e.g., randomized, placebo-controlled) and why it is
appropriate for the research question.
- Participant selection: Inclusion and exclusion criteria must be specified. Special
attention is required when studying conditions that are harder to define clinically (e.g.,
chronic fatigue syndrome), where diagnostic criteria need to be robust and well justified.
- Treatment plan: Detailed information on the study product, dosage regimen, route of
administration, duration, and how treatment compliance will be monitored.
- Efficacy and safety assessments: Criteria for measuring the therapeutic effect (e.g.,
cholesterol levels in a cholesterol study) and safety (e.g., adverse event monitoring).
- Statistical analysis: A description of the statistical methods used, including how
statistical significance will be evaluated. This section justifies the sample size and
outlines how primary and secondary outcomes will be analyzed.
- Data management and access: How data will be collected, stored, handled, and who
will have access to it. This ensures transparency and protection of sensitive information.
- Financial and insurance details: Information on trial funding, compensation, and
insurance coverage for participants in case of harm related to the trial.
1.3 STRUCTURED OVERVIEW OF PROTOCOL
A clinical trial protocol is organized into clearly defined chapters, each addressing a specific
aspect of the study. This structure ensures that the trial is scientifically sound, ethically
approved, and operationally feasible.
Summary Clinical studies 4
Inhoudsopgave
1 Protocol in a clinical trial ....................................................................................................... 3
1.1 Start-up of a clinical trial: Essential documents ...................................................................... 3
1.2 What Is a Protocol? ............................................................................................................... 3
1.3 Structured overview of protocol ............................................................................................. 4
1.4 Protocol content ................................................................................................................... 7
2 Legal framework for clinical research on humans in Belgium ................................................. 19
2.1 Old Legal framework ........................................................................................................... 19
2.2 “Old” Legal framework for clinical research in Belgium ......................................................... 20
2.3 “New” legal framework ....................................................................................................... 21
2.4 Why a New Legal Framework for Clinical Trials in the EU? ..................................................... 22
2.5 Why a New Legal Framework for Clinical Investigations (Medical Devices)? ........................... 24
2.6 Definitions .......................................................................................................................... 25
2.7 Scope ................................................................................................................................. 26
2.8 Actors Involved in Clinical Studies ....................................................................................... 28
2.8.1 Who Can Be the Principal Investigator (PI)? ...................................................................... 30
2.8.2 Sponsor .......................................................................................................................... 31
2.8.3 Non-Commercial Clinical Studies .................................................................................... 32
2.8.4 Accredited bodies ........................................................................................................... 33
2.8.5 Co-sponsorship .............................................................................................................. 33
2.8.6 CRO ............................................................................................................................... 34
2.9 Authorization procedure ...................................................................................................... 34
2.9.1 Remaining experiments ................................................................................................... 35
2.9.2 Clinical trials ................................................................................................................... 37
Europe: ..................................................................................................................................... 39
Belgium: .................................................................................................................................... 43
2.10 Transition period ................................................................................................................. 46
2.11 Vulnerable populations ....................................................................................................... 47
2.12 Liability and insurance......................................................................................................... 48
2.13 Summary ............................................................................................................................ 49
Summary Clinical studies 1
, 2.14 Conclusion ......................................................................................................................... 50
3 Clinical Trial Management Statistics .................................................................................... 50
3.1 General Statistical ideas...................................................................................................... 50
3.2 what endpoint? ................................................................................................................... 52
3.3 Fixed and Adaptive randomization schemes ......................................................................... 52
3.4 Representation of data ........................................................................................................ 53
3.5 Confidence Intervals for a mean (x̄) ...................................................................................... 53
3.6 Enrichment ......................................................................................................................... 58
3.7 Practical enrichment ........................................................................................................... 58
3.8 Prognostic enrichment ........................................................................................................ 58
3.9 Predective enrichment ........................................................................................................ 59
3.10 multiple testing ................................................................................................................... 60
3.11 confidence intervals give: .................................................................................................... 63
4 Study design ........................................................................................................................ 65
4.1 protocol writing ................................................................................................................... 65
4.2 Depression ......................................................................................................................... 65
4.3 Schizofrenie........................................................................................................................ 66
4.4 lipids .................................................................................................................................. 66
4.5 Vaccins .............................................................................................................................. 67
4.6 orphan diseases ................................................................................................................. 67
4.7 diabetes ............................................................................................................................. 68
4.8 cancer ................................................................................................................................ 69
5 informed Consent form (ICF) ................................................................................................ 69
5.1 informed consent process ................................................................................................... 69
5.2 informed consent form ........................................................................................................ 69
5.3 Content and recommendations * ......................................................................................... 70
5.3.1 Cover sheat .................................................................................................................... 70
5.3.2 Description of study and law participation ........................................................................ 71
5.3.3 informed consent ............................................................................................................ 72
Summary Clinical studies 2
,1 PROTOCOL IN A CLINICAL TRIAL
1.1 START-UP OF A CLINICAL TRIAL: ESSENTIAL DOCUMENTS
Starting a clinical trial requires several key documents and the completion of specific
procedures. More detailed information can be found on the UZ Leuven intranet under the
Clinical Trial Center (CTC), and on the official websites of the Ethics Committee (EC) and the
Federal Agency for Medicines and Health Products (FAMHP). Additionally, the CONSORT
guidelines (Consolidated Standards of Reporting Trials) are an important resource for the
proper reporting of clinical trials.
Commercial vs. Non-commercial Studies
A distinction is made between commercial and non-commercial clinical trials:
- Commercial trials are conducted on behalf of a sponsor, often a pharmaceutical
company.
- Non-commercial trials are initiated and conducted by a physician or researcher
without a commercial sponsor.
The classification also depends on the type of study — e.g., retrospective, observational, or
interventional.
Essential Documents for Trial Start-up
The following documents are crucial when starting a clinical trial:
- Protocol
- Informed Consent Form (ICF)
- Participant documents (questionnaire, diary,…)
- Recruitment materials
- Insurance
- Contracts with other departments/hospitals/companies/… (data property, publication
rights,…)
1.2 WHAT IS A PROTOCOL?
A clinical trial protocol is the foundational document that outlines how a clinical trial will be
conducted, how participant safety will be safeguarded, and how the integrity of collected data
will be maintained throughout the study. It serves as a comprehensive plan and must be strictly
followed once the trial begins.
Summary Clinical studies 3
, Purpose of a Protocol
The protocol demonstrates that the researchers have a thorough understanding of the study
they are conducting. It answers key questions such as:
- How will the trial be carried out?
- What safety measures are in place to protect participants?
- How will data be managed, analyzed, and kept reliable?
This document is often the first assignment in the development phase of a clinical trial and is
crucial for ethics approval and regulatory submission.
Core Components of a Protocol
A well-designed protocol contains the following elements:
- General information: Identification of the trial (title, ID), sponsor, investigators,
institutions involved, and responsible parties.
- Background and rationale: The scientific justification for the study. This includes a
summary of relevant preclinical data and prior clinical studies. It explains how dose
levels were determined and why the trial is necessary.
- Study objectives and design: A clear description of the trial’s goals and methodology.
This includes the choice of design (e.g., randomized, placebo-controlled) and why it is
appropriate for the research question.
- Participant selection: Inclusion and exclusion criteria must be specified. Special
attention is required when studying conditions that are harder to define clinically (e.g.,
chronic fatigue syndrome), where diagnostic criteria need to be robust and well justified.
- Treatment plan: Detailed information on the study product, dosage regimen, route of
administration, duration, and how treatment compliance will be monitored.
- Efficacy and safety assessments: Criteria for measuring the therapeutic effect (e.g.,
cholesterol levels in a cholesterol study) and safety (e.g., adverse event monitoring).
- Statistical analysis: A description of the statistical methods used, including how
statistical significance will be evaluated. This section justifies the sample size and
outlines how primary and secondary outcomes will be analyzed.
- Data management and access: How data will be collected, stored, handled, and who
will have access to it. This ensures transparency and protection of sensitive information.
- Financial and insurance details: Information on trial funding, compensation, and
insurance coverage for participants in case of harm related to the trial.
1.3 STRUCTURED OVERVIEW OF PROTOCOL
A clinical trial protocol is organized into clearly defined chapters, each addressing a specific
aspect of the study. This structure ensures that the trial is scientifically sound, ethically
approved, and operationally feasible.
Summary Clinical studies 4
