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Clinical studies - step by step

Clinical studies - step by step
  • Page contents:

    Health and medical care or clinical research?

    Compare your idea with previous research

    Search for knowledge among systematic analyses

    Search for gaps in scientific knowledge

    Use data found in registers

    Formulate the problem

    Särskilda regler för läkemedel och medicinteknik

  • Page contents:

    Research plan

    Statistical analysis plan

    Information to study participants

    Insurance for study participants

    Study budget

    Registering your study

    Handling of personal data

    Health economics evaluation

    Specific rules for clinical trials with medicines or medical devices

    Särskilda regler för läkemedel och medicinteknik

  • Page contents:

    Applying for an ethical review

    Applying for authorisation from a radiation protection committee

    Setting up a biobank

    Specific rules for clinical trials with medicines or medical devices

    SKL and LIF – agreements and templates for clinical studies

    Särskilda regler för läkemedel och medicinteknik

  • Page contents:

    Consent from study participants

    Access to information from medical records

    Collecting and managing data

    Specific rules for clinical trials with medicines or medical devices

    Särskilda regler för läkemedel och medicinteknik

  • Page contents:

    Statistical analysis plan

    Analysis population

    Replacement (imputation) of missing values

    Statistical analysis

    Adjustment analysis

    Subsidiary group analysis and interactions

    Sensitivity analysis

    Interim analysis

    Analysis database and analysis program

    Evaluating the result

    Writing a study report

    Särskilda regler för läkemedel och medicinteknik

  • Page contents:

    Writing a scientific article

    Selecting the journal

    Open access

    Särskilda regler för läkemedel och medicinteknik

  • Page contents:

    Personal data

    Specific rules for clinical studies using medicines

    Särskilda regler för läkemedel och medicinteknik

Planning

Read time 9 min

Once the problem formulation is completed and you know what questions are to be answered and what data need to be collected and analysed, the planning of your clinical study starts.

It is possible to get help with the planning process from Clinical Studies Sweden’s regional nodes or from specialists at your HEI if you are a researcher at an HEI or a university.

Research plan

Clinical studies carried out in Sweden require approval from an ethical review board. The ethical review application shall be accompanied by a complete and detailed research plan (also called a review plan). The research plan must include:

  • the scientific question including specific goals and the purpose of the proposed project
  • an area survey that summarises previous research findings within the research area
  • a project description, accounting for the design, selection of study participants including a calculation of population size, procedures, methods and definition of primary and secondary effect variables
  • a brief description of the project’s significance to the research area

If biobank samples are to be used in your clinical study, the biobank should be contacted early on in the planning. The biobank coordinator and the regional biobank centre can help you with advice in conjunction with planning, application templates, design of patient information and the biobank sections of the ethical review application.

The website of the ethical review boards includes guidelines for how the research plan shall be designed (pdf, 10kB) .external link, opens in new window

Statistical analysis plan

For open studies, a statistical analysis plan (SAP) shall be in place before the study starts, for blind studies before the database has been locked (further information on statistical analysis is available in the Analysis step). An SAP shall include:

  • detailed definitions of analysis populations
  • analysis variables
  • general description of the analyses
  • exact analysis methods for each analysis variable

Information to study participants

The information to be given to the study participants before they consent to participate in a clinical study shall include all the information that a person may reasonably need to know in order to decide whether or not to take part in a research project. The website of the ethical review boards includes guidelines for how the information shall be designed (pdf, 47kB)external link, opens in new window.

Insurance for study participants

The research principal for a clinical study shall ensure that there is insurance to cover any injury that may arise in conjunction with the implementation of the study. You will need to find out what insurance cover there is for the participants in your study, and check whether supplementary insurance needs to be arranged. The application to the ethical review board shall state whether the Swedish Patient Injury Insurance is valid, or if separate insurance needs to be arranged for the project.

Study budget

The financing of the project needs to be secured during the planning phase. There are a large number of Swedish and international research funding bodies, and researchers can also apply for grants and bursaries for which calls are published within the healthcare regions or by the universities in Sweden, the Nordic countries or the EU.

In order to carry out a clinical study, you should plan for resources in terms of time, money and personnel. A study budget is a calculation of all the costs in the project. The list of costs shall include items such as personnel, training, applications, agreements, data handling, programming, study medicines/medical devices, laboratory samples, statistical analysis, biobanks and administration. One item in the budget is monitoring, which is mandatory for studies involving medicines and medical technology non-CE marked products. The budget should be followed up regularly during the course of the project.

Registering your study

All clinical medicine studies must be registered in a publicly accessible database before the first study participant is recruited. All applications for medicine studies registered with the Medical Products Agency are also registered with the European study database EudraCTexternal link, opens in new window. The European Medicines Agency (EMA) is responsible for EudraCT. In USA, the Federal Drug Association (FDA) has the equivalent requirements for registration and result reporting of medicine studies. One way of registering the study is via clinicaltrials.govexternal link, opens in new window .

There is no registration requirement for studies that are not medicine studies, that is to say other therapy studies, observation studies, diagnostic studies or qualitative studies. However, it may still be beneficial to register your clinical study. WHO lists the following:

  • registering clinical studies is a prerequisite for enabling health and medical care to make well-informed decisions that take into account all available knowledge
  • it counteracts only some results being reported
  • unnecessary repetition of research can be avoided when researchers and funding bodies have the chance of finding information about similar or identical studies that have already been carried out
  • it makes it easier to understand where there are knowledge gaps
  • recruitment of study participants can be quicker if researchers and healthcare personnel can find information on ongoing studies more quickly
  • collaboration within clinical research becomes more efficient if researchers can find information about the studies that are in progress
  • research quality increases if reviewers can identify at an early stage studies where the study design can be improved

Many respected scientific periodicals require studies to be registered in order for the results to be approved for publication, and in practice there is thus often a registration requirement even for studies that are not therapy studies.

At clinicaltrials.gov, you can register your study even if it is not a medicine study.

Handling of personal data

Data protection regulation regulates if and how personal data may be handled for research purposes. The legal entity that handles the personal data in its operation and who decides on what data is to be handled, and what the data shall be used for is responsible for the handling of personal data (personal data controller).

Before starting your clinical study, you should find out what applies for handling of personal data within your organisation. The Data Protection Officer is a suitable person to contact.

Information about personal data management on the Swedish Data Protection Authority’s website (in Swedish)external link, opens in new window

Health economics evaluation

You should also consider whether to add a health economics evaluation to your study. Such an evaluation discovers whether a medical intervention is cost effective, that is to say whether there is a reasonable relationship between cost and effect as measured in improved health and increased quality of life, or Health Related Quality of Life (HRQoL).

In SBU’s handbook Assessments of methods in healthcare you can read more on health economics evaluation (pdf, 1796 kB)external link, opens in new window. The Dental and Pharmaceutical Benefits Agency, (TLV), has information about health economics evaluationexternal link, opens in new window on its website.

Specific rules for clinical trials with medicines or medical devices

A trial protocol is required for the application to the Medical Products Agency

For most clinical studies using medicines or medical devices, authorisation from the Medical Products Agency is also required. The Medical Products Agency’s website has a test to help you determine whether or not your study requires authorisation from the Medical Products Agency (pdf, 154 kB, in Swedish)external link, opens in new window.

A trial protocol must be appended to the application to the Medical Products Agency. For medicine studies involving several clinics, the trial protocol forms the basis for uniform implementation and shall include all the information needed to ensure the participating clinics conduct the study correctly. On its website, the Medical Products Agency provides information on how to conduct clinical trials with medicinesexternal link, opens in new window.

Allocating roles and responsibilities in accordance with Good Clinical Practice

Good Clinical Practice (GCP) is an international ethical and scientific quality standard for designing, conducting and reporting on clinical studies using medicines or medical devices. The purpose of GCP is to safeguard the rights, safety and well-being of the study participants. For medicine studiesexternal link, opens in new window, GCP is defined by the International Conference on Harmonisation (ICH)external link, opens in new window, which includes US, European and Japanese medicine authorities. For clinical trials involving medical devicesexternal link, opens in new window, an international standard is used that is harmonised with the GCP standard for medicines as far as possible. SIS, the Swedish Standards Institute, is a standardisation organisation tasked with issuing standards (such as a standard for GCP for medical devices) within all operational and societal areas. All Swedish healthcare personnel have access to these standards via internet by means of an agreement between SIS publishers and SKL (in Swedish)external link, opens in new window.

Common questions about GCP on the European Medicines Agency’s websiteexternal link, opens in new window

More on the allocation of responsibility in the Medical Product Agency’s regulations on clinical medicine trials on human subjects (pdf, 96 kB, in Swedish)external link, opens in new window

According to GCP, there are a number of roles with varying responsibility to allocate when planning to carry out a clinical study using medicines or medical devices.

The sponsor is the physical person or legal entity responsible for starting, organising and/or financing the study. In some cases, an individual can be both the sponsor and the principal investigator, and is then the person who both initiates and leads a clinical study. The role thus includes the obligations of both the sponsor and the principal investigator.

The sponsor has overall responsibility for the implementation of the study, and is responsible for issues such as:

  • ensuring there are written instructions for work, quality control and quality assurance
  • ensuring instructions are complied with
  • ensuring the study participants are guaranteed financial protection by means of insurance or otherwise

The sponsor may delegate all or parts of its tasks to an individual person, a company, an institution or an organisation, but the sponsor retains responsibility for ensuring the study is conducted and reported according to the applicable authorisations and rules.

The clinical investigator shall be a registered medical doctor or dentist and shall have the qualifications in the form of the education, training and experience required to take responsibility for the implementation of the study and the health and safety of the study participants, including documented training in GCP.

Some of the tasks of the clinical investigator are:

  • to provide the prerequisites for recruiting the agreed number of study participants and to set aside sufficient time to implement the study
  • to appoint qualified personnel who can help in the implementation of the study and also monitor delegated personnel in order to safeguard all processes
  • to take responsibility for delegated personnel receiving suitable training on the study
  • to ensure information on the study is provided, and that consent to participate is obtained according to the applicable rules
  • to draw up procedures for saving all study documentation and to allow monitoring and audit
  • to allow monitoring and audits

The clinical investigator has overall responsibility for the study, but may delegate tasks on condition that the delegation is done in writing. For this reason, a signature and delegation list must be drawn up and kept updated in the event of any personnel changes during the course of the study. A task must first be delegated before it may be executed by any person other than the clinical investigator.

If there is more than one clinical investigator at a trial site, the sponsor may appoint one of them to be the principal investigator.

The monitor is a person appointed by the sponsor, whose responsibility it is to monitor the development of a clinical study, by carrying out tasks such as:

  • ensuring on location that the study is conducted, documented and reported according to the protocol, GCP and applicable public agency requirements
  • submitting a written report to the sponsor following each visit to the study site and to report on other study-related communication

In order to enable the monitor to monitor a study, he or she needs to have scientific and/or clinical prior knowledge, and also knowledge about:

  • the product being tested
  • the protocol
  • study participant information
  • the sponsor’s procedures
  • GCP
  • regulatory requirements

Set up systems for data collection, data processing and data storage

Data on the study participants in a clinical medicine study shall be collected into a data collection form, a Case Report Form (CRF). You can choose between setting up the system in paper format or electronic format. Electronic CRF (eCRF) may constitute the foundation for the database that is created for analyses, while paper CRF need to be converted into electronic data at a later stage. The material must be saved and be readable for at least ten years after the study has been concluded and reported.

You also need to write plans for data handling (Data Management Plan, DMP) and data validation (Data Validation Plan, DVP).

Särskilda regler för läkemedel och medicinteknik

To consider

  • Is the research plan complete?
  • Is there information to and insurance for the study participants?
  • Has a biobank been contacted?
  • Is there a budget?
  • Does the study need to be registered?
  • Is the study a clinical trial? If so, there are special rules concerning allocation of responsibility and data handling.

Skapad: 2017-11-10
Senast uppdaterad: 2018-12-11 

Contact

Office for Clinical Studies, Swedish Research Council

Östra Hamngatan 26
SE-411 09 Göteborg

 

Phone (Swedish Research Council, switchboard):
+46 (0)31 757 41 75

E-mail: kliniskastudier@vr.se

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Clinical Studies Sweden - a collaboration between The Swedish Research Council and the Swedish Association of Local Authorities and Regions.