Each subsection below includes two parts. The subsection opens with an explanation of the subject and guidance on how to address it. This is followed by a list of tools that have been identified in relation to this subsection. The tools listed may not be unique to clinical trials in rare diseases, this is specified in the table to better understand the use of the tool. You can visit the different section by clicking on the buttons above or return to the full toolkit here.
Risk assessment is a systematic process for identifying and evaluating events that could affect the achievement of clinical study objectives related to quality, safety, timelines and budget, positively or negatively.
Some academic organisations may not be in a position to undertake the role of sponsor for clinical trials or may only sponsor trials of a certain risk level. It is essential therefore that a risk assessment is undertaken at the very start. The process could be defined such that the risk assessment is undertaken on the research proposal and then further refined once the protocol has been drafted.
The risk-based approach relies on the identification and assessment of risk(s) and mitigation of these risks.
For years, risk has been interpreted as the risk for patient's safety or rights only. However, other types of risk should be considered: the institutions and teams in charge of the study conduct, the governance structures, the target population, the public health stakeholders, etc.
The risks of a clinical trial depend on a number of factors but can be broadly categorised as:
• the risks of the investigational medicinal product (IMP)
• the risks associated with the regulatory and legal requirements, the trial conduct, design and methods
The OECD Recommendation on the governance of Clinical Trials introduced a risk-based oversight and management methodology for clinical trials. It combines a stratified approach that is based on the marketing authorisation status of the medical product and can be applied in a common manner across countries’ regulatory frameworks, with a trial-specific approach that considers other issues such as the type of populations concerned by the trial, or the informed consent of the patients. EMA Reflection paper on risk-based quality management in clinical trials (2013) and EC considerations on Risk Proportionate approaches in clinical trials (2017) aim to facilitate the development of a systematic, prioritised, risk-based approach to quality management of clinical trials, to support the principles of Good Clinical Practice and to complement existing quality practices, requirements and standards.
|Tool Name||Relevance||Year||RD/Paediatric specific||Type|
|OECD Recommendation on governance of clinical trials||To facilitate international co-operation in clinical trials on medicinal products, particularly for trials initiated by academic institutions, in December 2012 the OECD Council adopted a set of principles calling for improved consistency among national regulations and their interpretations, and on streamlined procedures for the oversight and management of clinical trials. This framework introduces a risk-based oversight and management methodology for clinical trials.||2013||No||Recommendation|
|Guideline on strategies to identify and mitigate risks for first-in-human and early clinical trials with investigational medicinal products||The guideline is intended to further assist stakeholders in the transition from non-clinical to early clinical development and in identifying factors influencing risk for new investigational medicinal products (IMPs). The document includes considerations on quality aspects, non-clinical and clinical testing strategies, study design and on the conduct of FIH/early CTs||2017||No||Guideline|
|Risk assessement form for clinical research projects||Swiss Clinical Trials Organisation Tools: Risk Assessment of potential risks of a clinical research project-in line with current requirements (ICH GCP E6(R2))||Regular updates||No||Guideline|
TRIAL MANAGEMENT PLAN
The purpose of a Project Management Plan (PMP) in a clinical trial is to define the scope, outline responsibilities and describe key steps of the clinical trial process. This not only ensures that those performing the tasks have a clear plan of what, when and how the trial activities are undertaken, but also enables auditors/inspectors to reconstruct how a trial was managed. Trial management procedures/responsibilities that are common across all trials are usually defined in the sponsor’s research standard operating procedures (SOPs)/policies and for less complex trials, the trial management documentation may simply consist of an index of these SOPs with any trial-specific management described in sufficient detail in the protocol. The level of detail required will depend upon:
a) The clinical trial risk assessment
b) The organisational structure within which the clinical trial is conducted
c) The design and methods of the clinical trial
The trial management plan should outline procedures regarding:
- Documentation (Trial Master File)
- Investigational product
- Site management
- Safety plan
- Data management (Data Management plan)
|Tool Name||Relevance||Year||RD/Paediatric specific||Type|
DATA MANAGEMENT PLAN (DMP)
DMP is a written document that describes the plans for collection and management of data throughout the lifecycle of a clinical trial. The DMP describes which clinical data will be acquired and how it will be handled, stored, checked for consistency and plausibility, and made available for the final analysis and further research after the end of the project.
For effective data management, planning must begin at the time of trial design. It should consider the collection and management of data during the trial, data sharing and archiving at trial closure. A well-designed DMP will provide a road map on how to handle the data, establish processes to handle unforeseeable conditions and assess potential risks.
As there are various stakeholders and staff members involved in data handling, the key goal of this document is to communicate to each stakeholder the required information to create and maintain a high-quality database that is ready for analysis. In addition to the database specification, DMP should also document CRF (Case report Form) design and development.
It is considered best practice to develop the DMP in collaboration with all stakeholders involved in the trial, to ensure compliance. Institutes and agencies involved in clinical research might consider developing DMP templates, which are customised as per the requirements of the trial.
Typical data management plan elements:
- Data collection: Types of data, contextual details (metadata)
- Data Storage: Storage, backup and security
- Data Protection: Access, monitoring, provisions for protection/privacy
- Policies for re-use
- Access and sharing
|Guidelines for effective Data Management Plan||Guidance to create Data Management plans developed by the Inter-university Consortium for Political and Social Research (ICPSR), an international consortium of academic institutions and research organizations.||Regular updates||No||Guideline|
|Data Management Plan Online||Templates for data management plans based on the specific requirements listed in funder policy documents.||Regular updates||No||Template|