Good Clinical Practice (GCP)
Good Clinical Practice (GCP) is an international ethical and scientific quality standard for designing, conducting, recording, and reporting trials that involve the participation of human subjects.
Compliance with this standard provides public assurance that the rights, safety and well-being of trial subjects are protected, and that the trial data is credible.
Everyone involved in the conduct of clinical research must have training in Good Clinical Research to ensure they are best prepared to carry out their duties.
This is laid down in the Research Governance Framework for Health and Social Care 2005, covering all research in the NHS in England, and in law for those people working on clinical trials.
The principles of GCP state that: each individual involved in conducting a trial should be qualified by education, training and experience to perform his or her respective task(s).
For information on GCP training, please see Training (below).
The principles of GCP
- Clinical trials should be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki, and that are consistent with good clinical practice (GCP) and the applicable regulatory requirements.
- Before a trial is initiated, foreseeable risks and inconveniences should be weighed against the anticipated benefit for the individual trial subject and society. A trial should be initiated and continued only if the anticipated benefits justify the risks.
- The rights, safety, and well-being of the trial subjects are the most important considerations and should prevail over interests of science and society.
- The available nonclinical and clinical information on an investigational product should be adequate to support the proposed clinical trial.
- Clinical trials should be scientifically sound, and described in a clear, detailed protocol.
- A trial should be conducted in compliance with the protocol that has received prior institutional review board (IRB)/independent ethics committee (IEC) approval/favourable opinion.
- The medical care given to, and medical decisions made on behalf of, subjects should always be the responsibility of a qualified physician.
- Each individual involved in conducting a trial should be qualified by education, training and experience to perform his or her respective task(s).
- Freely given informed consent should be obtained from every subject prior to clinical trial participation.
- All clinical trial information should be recorded, handled and stored in such a way that allows its accurate reporting, interpretation and verification.
- The confidentiality of records that could identify subjects should be protected, respecting the privacy and confidentiality rules in accordance with the applicable regulatory requirements.
- Investigational products should be manufactured, handled and stored in accordance with applicable good manufacturing practice. They should be used in accordance with the approved protocol.
- Systems with procedures that assure the quality of every aspect of the trial should be implemented.
The Principal Investigator's (PI's) responsibilities
The Chief Investigator (CI) is the person designated overall responsibility for the design, conduct and reporting of a study in the UK.
However, as mostly a participating site, the main role in the Trust is that of PI.
If you are the PI on a research study, it is your responsibility to ensure that:
- The dignity, rights, safety and well-being of participants are given priority at all times by the research team.
- The research is carried out in accordance with the Research Governance Framework.
- The appropriate approvals are given before the research commences.
- The available non-clinical and clinical information on an investigational product is adequate to support the proposed clinical trial.
- When a study involves participants under the care of a doctor, nurse or social worker for the condition to which the study relates, those care professionals (both within and outside the Trust) are informed that their patients or users are being invited to participate and agree to retain overall responsibility for their care.
- When the research involves a service user or carer or a child, looked after or receiving services under the auspices of the local authority, the agency director or deputy agrees to the person (and/or their carer) being invited to participate and is fully aware of the arrangements for dealing with any disclosures or other relevant information.
- The study complies with all legal and ethical requirements.
- Each member of the research team is qualified by education, training and experience to discharge their role in the study.
- Students and new researchers have adequate supervision, support and training.
- The research follows the protocol approved by the relevant ethics committee and the research sponsor.
- Any proposed changes or amendments to, or deviations from, the protocol are submitted for approval to the ethics committee, the research sponsor and any other appropriate body.
- Procedures are in place to ensure the collection of high quality, accurate data and the integrity and confidentiality of data during processing and storage.
- Arrangements are made for the appropriate archiving of data when the research has finished.
- Reports on the progress and outcomes of the work required by the sponsor, funders, or others with a legitimate interest are produced on time and to an acceptable standard.
- The findings from the work are opened to critical review through the accepted scientific and professional channels.
- Once established, findings from the work are disseminated promptly and fed back as appropriate to participants.
- He/she accepts a key role in detecting and preventing scientific misconduct by adopting the role of guarantor on published outputs.
- Arrangements are in place for management of financial and other resources provided for the study, including the management of any intellectual property arising.
- All data and documentation associated with the study are available for audit at the request of the appropriate auditing authority.
A key requirement for anyone involved in the conduct of clinical research is Good Clinical Practice (GCP) training. GCP is the ethical and practical standard to which all clinical research is conducted.
Everyone involved in the conduct of clinical research must have training to ensure they are best prepared to carry out their duties.
This is laid down in the Research Governance Framework for Health and Social Care 2005, covering all research in the NHS in England, and in law for those people working on clinical trials.
The principles of GCP state that "each individual involved in conducting a trial should be qualified by education, training and experience to perform his or her respective task(s)".
[2.8, E6 Guideline for Good Clinical Practice]
How often you need to complete GCP training
This is decided by your Trust/Employer, as the answer depends on the research you are involved in and your experience.
Within Great Western Hospitals NHS Foundation Trust the requirement is to undertake GCP training every two years.
Research and Innovation is in the process of setting up Introduction to GCP courses for staff involved in Research at the Trust.
More details about how to book these courses will appear here shortly.
More information on external GCP courses can be found on the Clinical Research Network website.
You need to ensure that you or your team have the necessary expertise to carry out the research before starting on the project.
If you don't have the required expertise, you need to collaborate with someone who does.
To discuss you training requirements and options, please contact the Research and Innovation team.
For more details please contact us.
Roles and responsibilities
All members of the team must strictly follow the agreed protocol and collect the agreed data.
If you are involved in research on Trust patients you also have an obligation to ensure that they are treated ethically and safely at all times.
Research and Innovation Team
The Research and Innovation are responsible for making sure that all the required approvals are in place before the research commences, and that the delivery and governance of the research is in accordance with what was agreed with the sponsor.
Delegation is essential for the success of a trial.
Specific tasks will need to be delegated downwards between different members of the trial team.
Initially a contract between the sponsor and the host organisation will delegate who does what at a high level.
Once the contract is agreed the Principal Investigator (PI) should delegate trial specific task to his team.
All roles and duties must then be documented in a delegation log.
Risks and mitigation
All trials carry some risk to the researchers, the patients, the sponsors and the Trust.
Protocols are designed to minimise trial risks and sponsors will monitor that it is being followed.
Trial leaders will be asked to complete a risk assessment before sponsorship is agreed.
Monitoring and inspection
Any trial is liable to inspection/audit by the Research and Innovation Team at any time.
Trials involving medicines are monitored by the Research and Innovation department and the trial sponsor.
An inspection by the MHRA is also possible.
All will be checking to see that you have followed the protocol and that the terms of the contract have been adhered to.
Below are some examples of what might be checked:
- Filing of trial paperwork is appropriate and complete. This is at the heart of any trial and is vital to its success.
- The sponsor's approval of amendments is recorded.
- Entries in the patient notes match the date of consent/visit schedule.
- Evidence that medical results have been reviewed in a timely manner exists.
- Safety reporting is in line with the protocol
- Data in the trial database matches the source/patient notes.
- Clinical confirmation of eligibility is in the data set/patient notes.
- Descriptions of how samples are collected, stored, transported or processed.
- Contracts are in place with third parties.
Recruitment of trial subjects
Recruitment is the process by which:
- Eligible patients are identified
- And approached to determine if they are willing to consent to participate in the study
Each protocol identifies the inclusion and exclusion criteria for potential participants
- Inclusion: criteria which must be present to address the study question
- Exclusion: criteria which may mean the study is not safe for the potential participant, or their involvement might undermine the scientific basis of the study
Informed consent of trial subjects
Before informed consent may be obtained, the investigator should provide the subject with ample time and opportunity to inquire about details of the trial and to decide whether or not to participate in it.
All questions about the trial should be answered to the satisfaction of the subject.
Investigators should not coerce or unduly influence a subject to participate or to continue in a trial.
The language used in all the oral and written information about the trial should be as non-technical as practical and should be understandable to the subject or their representative.
Prior to a subject's participation in the trial, the written informed consent form should be signed and personally dated by the subject (or subject's representative) and by the person who conducted the informed consent discussion.
Both the informed consent discussion and the written informed consent form and any other written information to be provided to subjects should include an explanation on the following:
- That the trial involves research.
- The purpose of the trial.
- The trial treatment and the probability for random assignment to each treatment.
- The trial procedures to be followed.
- The subject's responsibilities.
- The aspects of the trial that are experimental.
- The reasonably foreseeable risks and/or inconveniences to the subject
- The reasonably expected benefits. Where there is no intended clinical benefits to the subject, they should be made aware of this.
- The expected duration of the subject's participation in the trial.
Prior to participation in the trial, the subject should receive a copy of the signed and dated informed consent form.
A Screening Log should be maintained to demonstrate:
- Timeline of introduction, approach, discussion and consent process
- Number of people assessed for eligibility
- Number of people approached to join the study
- Number of declined offers and reasons for declines
- Number recruited to the study
The Site File is a collection of documents that allows the conduct of the study on Site, the integrity of the data and compliance with the protocol to be evaluated
- It should be maintained throughout the study and archived when the study is complete
- It should contain all the relevant documents received at Site relating to a specific study
- Under GCP guidelines, the Site File must contain all the essential documents pertaining to a study
Amendments are changes made to the study conduct or documentation after a favourable ethical opinion has been given by the Research Ethics Committee (REC).
A 'substantial amendment' is defined as an amendment to the terms of the application, or to the protocol, that is likely to affect to a significant degree:
- the safety or physical or mental integrity of the subjects of the study
- the scientific value of the study
- the conduct or management of the study
- the quality or safety of any investigational medicinal product used in the trial.
The PI is responsible for ensuring that any substantial amendments are implemented at site, and that measures are put in place to check that everyone is working to the right version of all the documents following the amendment.
The process of conducting research begins with the gathering of source data from participants as directed by the Protocol.
Source data is the first record of any interactions with participants and is the foundation of all other activity in the trial.
Comprehensive source data supports effective patient care and helps maximise the contribution that individual participants make to research.
- With every participant during any trial activity you should:
- Recheck their willingness to continue in the trial
- Discuss how they are feeling and how they have been since you last saw them
- Check baseline clinical information and any concomitant medications
- Conduct the required specific trial procedures
- Record a summary of your discussions and specify the activities completed in the participant's patient notes as well as detailing the data gathered during the study related procedures.
Electronic source data is common in primary care where patient notes are recorded directly into electronic systems. Good practice is to print, sign and date each entry and store this in the Site File.
Completing Clinical/Case Report Forms (CRFs)
CRFs should provide the sponsor with only the data they need to answer the research question.
The transfer of data should be done carefully and correctly to avoid unnecessary data queries.
CRFs are only as good as the source sata.
Until the CRF is completed and sent to the sponsor, your study activity is not visible or usable by the sponsor.
The sponsor uses data throughout the study to ensure participants are safe and the study conduct is appropriate.
Carefully copy the data required from the source data to the CRF.
Ideally this should be done the same day as the source data was collected or shortly afterwards.
Integrate completion of the CRF into your daily work routine where possible to ensure timely reporting of the data to the sponsor.
Mistakes and omissions when completing the CRF result in data queries being generated by the sponsor.
Avoid this duplication of effort by ensuring that the CRF is completed correctly the first time.
Things to look out for:
- The participant's initials and ID number are completed correctly and consistently
- Dates and numbers are completed consistently
- All required data fields have been completed
- Any changes are correctly entered
Deviations from the protocol
Mistakes will sometimes occur and unavoidable events will lead to deviations.
These should be reported to the sponsor as soon as possible.
You should also document what happened in the patient notes and in a file note in the Site File.
As much detail as possible should be captured to ensure that the events can be reconstituted and verified.
Any correspondence and records of telephone conversations should also be kept
Remember: if it is not documented, it 'did not happen'.
Every effort should be made to ensure compliance with the Protocol and deviations from it should not be commonplace.
"A serious breach is a breach which is likely to effect to a significant degree:
a) The safety or physical or mental integrity of the subjects of the trial, or
b)The scientific value of the trial."
[Medicines for Human Use (Clinical Trials) Regulations 2004]
Ensuring the safety of participants and scientific value of the study is essential for all types of clinical research.
It is essential that a serious breach is acted upon immediately as notification must be made to the MHRA within seven days of the sponsor becoming aware of the breach.
It is everyone's responsibility to do this.
Systematic failures left unchecked or identified and ignored put participants at risk and undermine the validity of the research and the contribution made by each participant.
As soon as a Serious Breach has been identified, the Sponsor should be notified.
If the study is a CTIMP the Sponsor is also required to inform the MHRA.
Any additional actions required by the Sponsor or MHRA require to investigate or address the breach should be completed as soon as possible.
An 'adverse event' is any untoward occurrence that happens during the conduct of the trial.
The event may be as a result of the trial conduct of intervention, or may have no relationship to it at all.
All adverse events should be recorded in the participant's patient notes in as much detail as possible.
Serious Adverse Events (SAEs)
There are three questions that should be asked to determine whether an adverse event can be categorised as an SAE:
Question 1: Is it serious?
The standard definition of an SAE is an event which:
- Results in death
- Is life-threatening
- Requires hospitalisation or prolongation of existing hospitalisation
- Results in persistent or significant disability or incapacity
- Consists of a congenital anomaly or birth defect
Check the definition of 'serious' in the protocol as it may be amended to reflect the likelihood of occurrence in a particular trial.
Question 2: Can it be attributed to the study?
The decision whether an event has been caused by a trial procedure or trial drug must be made by a medically qualified person who has been delegated the responsibility of assessing adverse events.
Decisions about causality must be made at Site and must involve the PI.
Neither the sponsor or CI can change the Site's assessment of causality, even if they do not agree.
Question 3: Is it consistent with the available information?
The extent to which an event could be expected is determined by comparing the symptoms with the available information related to the trial procedures or trial drug.
References for all studies will be found in the protocol and Patient Information Sheet.
All SAEs should be reported immediately upon knowledge of the event.
Study closer gives a final opportunity to ensure all data is complete and accurate.:
- Complete any outstanding data queries or gather any missing data
- Ensure all essential documents are archived safely and appropriately