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This is the ‘active’ stage of a research study after all research approvals and permissions are in place and recruitment of participants and/or data collection begins. This stage occurs when the researchers start to follow the procedures as described in the protocol. It is a busy time usually and researchers need to be vigilant in their documentation and their reporting responsibilities to all the authorities who have a legitimate interest in the research study; these will include the ethics committee, the regulatory body, the funder, the NHS Trust, the University, the employer. Any changes to the protocol need to be dealt with following the due processes.

Keeping oversight of the conduct of a research study overall is the responsibility of the Chief Investigator and locally the Principal Investigator is responsible for the conduct of the research study at their site. This will include, of course, ensuring participant safety, rights and wellbeing and it also includes ensuring research team availability and expertise.

Delivery of a research project to “time and target” means the researchers have recruited the agreed number of participants in the agreed time. Research teams are monitored closely to ensure they meet their performance targets.

Conduct, Amendments & Urgent Safety Measures


The Chief Investigator (CI) is responsible for the conduct of the research project overall and should be fully aware of what is going on across all sites. The CI should have understanding and knowledge of the rules and regulations that govern research in the NHS. For a clinical trial involving an investigational medicinal product (CTIMP), it is illegal for a person to conduct a clinical trial or perform the functions of the sponsor of a clinical trial (whether that person is the sponsor or is acting under arrangements made with that sponsor) otherwise than in accordance with the conditions and principles of good clinical practice as provided in the UK Clinical Trial Regulations (Schedule 1).

In practice, and especially in non-commercial research, many of the responsibilities of the sponsor are delegated to the Chief Investigator/research team or a clinical trials unit for larger multi-centre studies.

The Principal Investigator (PI) is responsible for the conduct of the research project at their site and should be able to demonstrate effective communication and oversight of the study; an up-to-date delegation log and a well maintained Site File should go a long way in demonstrating this.

Investigators involved in any type of clinical trial, but particularly those involved in CTIMPs, should undertake regular Good Clinical Practice (GCP) training. It is Bradford Teaching Hospitals NHS Foundation Trust policy that Investigators involved in CTIMPs should be able to demonstrate recent GCP training. Recent training is defined as within the last two years or sooner if there are changes to the regulations and/or guidance. This applies to all who are involved the study.

In practice, being responsible for overseeing a study’s conduct means –

  • Ensuring that the Study is managed, monitored and reported as agreed in the Protocol.
  • Ensuring that no Participant is recruited to the Study until the PI is satisfied that all relevant regulatory permissions and approvals have been obtained.
  • The CI being responsible for the ongoing assessment of participant wellbeing and safety for the duration of the Study and reporting to the Research Ethics Committee (REC) in accordance with the conditions of the REC Favourable Opinion.
  • Reporting suspected research misconduct immediately.
  • Ensuring that the Study adheres to the guidance as given by the ethics committee with regard to identification, recruitment and enrolment of participants.
  • Ensuring the Study adheres to the terms of the Clinical Trial Authorisation issued by the MHRA.
  • The CI maintaining detailed records of all adverse events reported by Investigators (unless otherwise specified in the Protocol) and ensuring that all investigators are, at all times, in possession of the current relevant safety information for the Study.
  • The CI complying with all reporting requirements with regard to safety and progress within the reporting timeframes to the relevant ethics committee, the MHRA and any other authority with a legitimate interest. These reports will include expedited safety reporting, annual progress reports and annual safety reports to the ethics committee and MHRA. The forms and guidance are available from the HRA website at The PI complying with all monitoring reports to their R&D Office.
  • The CI notifying the ethics committee and the MHRA (for a CTIMP) in writing when the Study has finished within 90 days of the conclusion of the Study. The end of study declaration form is available from the HRA website, The PI notifying the R&D Office of the Study’s end date at site.
  • The CI notifying the ethics committee and the MHRA (for a CTIMP) if the Study is terminated early in accordance with timefames. If the Study is prematurely terminated or suspended for any reason, the Chief Investigator is responsible for ensuring there is a process in place for informing the Study participants, ensuring appropriate therapy and follow-up for the participants.
  • Intellectual Property (IP) can be created where research, delivery or management of care or other creative work is being undertaken. Researchers should notify their employer should any IP issues arise during the life of the Study.
  • Amendments

    The sponsor may make an amendment to a research project at any time. The sponsor is responsible for the assessment of substantiality of proposed amendments and for sending a valid notice of amendment to the ethics committee and the MHRA (for a CTIMP).

    The sponsor is responsible for ensuring that amendments are not implemented at the study sites until HRA, ethics committee and MHRA approval (for a CTIMP and if applicable) and any other necessary permissions are in place. The forms and guidance are available from the HRA website at The PI is resposible for assesment of ongoing capacity capability to deliver the research at their site.

    Urgent Safety Measures

    The sponsor and investigator may take appropriate urgent safety measures in order to protect the subjects of a clinical trial against any immediate hazard to their health or safety. If this is the case, the sponsor is responsible for notifying the ethics committee and the MHRA (for a CTIMP) immediately in writing of any ‘urgent safety measures’ and no later than 3 days from the date the measures were taken (Regulation 30 of the UK Clinical Trial Regulations). The protocol should stipulate the procedure and timelines for reporting an ‘urgent safety measure’ to the sponsor to enable the sponsor to comply with this regulatory requirement.


Progress & Safety Reporting

The UK Policy Framework for Health and Social Care Research aims to forestall adverse incidents and ensure that lessons are learned and shared when incidents are identified. It states that it is the responsibility of the researcher to report any adverse events in accordance with their organisaiton’s standard reporting procedures, and that organisations are responsible for reporting through the normal incident reporting channels.

The sponsor should ensure mechanisms are in place to be informed of all adverse events and progress of the study.

Researchers should return completed monitoring reports to their R&D Office in a timely manner. Other reporting requirements include –

Funders External funders usually require financial updates and/or progress reports, these tend to be required annually. The details will depend on the funding body and should be outlined in the terms and conditions of the grant award. For studies that aim to recruit large numbers of participants, the funding body may wish to be updated on whether recruitment targets are being met.

Research Ethics Committee (REC) Ethics committees require updates on progress and to be informed of any safety issues. Information is available on the HRA websiteand there is specific guidance for annual progress reports and safety reporting in clinical trials involving medicinal products (CTIMPs) and studies other than CTIMPs. Expedited reporting is required for serious adverse events and researchers should be aware of their responsibilities and timelines.

Medicines and Healthcare Products Regulatory Agency (MHRA) The regulations distinguish between Adverse Events (AEs), Serious Adverse Events (SAEs), Serious Adverse Reactions (SARs) and Suspected Unexpected Serious Adverse Reactions (SUSARs). The trial sponsor must be notified of SAEs immediately. Sponsors have to make sure that SUSARS are reported promptly to both the regulatory authorities and the relevant Research Ethics Committee (REC). The Regulations set time limits.

An investigator should report any serious adverse event which occurs in a subject at a trial site at which s/he is responsible for the conduct of a clinical trial immediately to the sponsor in accordance with the sponsor’s instruction. The sponsor must keep detailed records of all adverse events relating to a clinical trial which are reported to him by the investigators for that trial. A sponsor should ensure that all relevant information about a SUSAR (suspected unexpected serious adverse reaction) which occurs during the course of a clinical trial in the UK and is fatal or life-threatening is recorded and reported as soon as possible to the MHRA, the competent authorities of any European Economic Area (EEA) State in which the trial is being conducted, and the relevant research ethics committee, and in any event not later that 7 days after the sponsor was first aware of the reaction. A sponsor should ensure that within 8 days of a report any additional relevant information is sent to the persons or bodies listed above. All other SUSARs that are not fatal and non-life threatening must be reported as soon as possible and in any event not later than 15 days after the sponsor is first aware of the reaction.

EudraLex – Volume 10 Clinical trials guidelines –  The rules governing medicinal products in the European Union contains guidance documents applying to clinical trials.

There are stations in the Clinical Trials Tool Kit and the Data and Tissues Tool Kit that provide further guidance for researchers with regard to reporting.

Reporting Serious Breaches of Protocol and Good Clinical Practice

For a clinical trial that involves an investigational medicinal product (CTIMP), the sponsor is responsible for notifying the relevant ethics committee and the Medicines and Health Products Regulatory Agency (MHRA) in writing of any ‘serious breach’ of the protocol or of the conditions and principles of good clinical practice within 7 days of becoming aware of it (Regulation 29A of the UK Clinical Trial Regulations).

For the purposes of the UK Clinical Trial Regulations, a “serious breach” is a breach which is likely to effect to a significant degree –

  • the safety or physical or mental integrity of the subjects of the trial; or
  • the scientific value of the trial.

The Protocol should stipulate the procedure and timelines for reporting a serious breach to the sponsor to enable the sponsor to comply with this regulatory requirement.

An investigation will follow of the incident and a decision will be made as to whether the study should continue in its current form, continue with new arrangements in place or be terminated early.

Reporting Performance

R&D Offices are required to report research performance on a regular basis to the NIHR (National Institute for Health Research) local networks and the Department of Health. It is, therefore, important that research teams track and analyse their own performance and keep accurate, real-time data so that the recruitment information required by the R&D Office is readily available.


Sponsor Oversight

All studies have an element of oversight by the Sponsor which will vary based on the type of Study (eg, clinical trial involving an investigational medicinal product (CTIMP), non-CTIMP) and the risk management plan completed during the Sponsor Decision process.

Most sponsors use a risk-based approach to overseeing and monitoring research.

Oversight activities provide quality control checks or functions which ensure that all studies, have the proportionate amount of quality control and management in place to protect the Sponsor.

Oversight can consist of:

  1. Monitoring (including audit)
  2. Review of External Agreements
  3. Study tracking

Organisational Oversight

The role of the R&D Office is to provide organisational oversight of a study’s conduct. The approach taken for each Study should be proportionate to the risks associated with the study and the level of monitoring and support being undertaken by the sponsor. Typically, R&D Offices’ oversight activities will include the following and will utilise a risk-based approach –

  1. Study Tracking by annual progress reports and end of study declaration report
  2. Issue Management –
    • Managing External Agreements.
    • Managing Internal Agreements.
    • Managing Study Processes.
    • Managing Research Passports
    • Managing Performance
  1. Audit Priority is normally given to studies with the higher risk scores, clinical trials involving an investigational medicinal product(s) (CTIMPs), NIHR portfolio studies, and studies sponsored by the organisation. Some low risk studies may not be subject to scheduled audit at all.

Principal Investigator Oversight

One of the most common inspection findings is lack of demonstrated Principal Investigator (PI) oversight. It is entirely acceptable for the PI at a research site to delegate tasks and responsibilities to other members of the research team who are adequately trained and experienced to undertake them, however, the PI cannot delegate their responsibility entirely and must at least retain oversight of the conduct of the research at their site.

During the conduct of a research study there are key events where the PI should “sign-off” their involvement, eg, confirming the study can commence when all the necessary research approvals and permissions are in place, completing the delegation log, confirming a participant’s eligibility to take part in the study, confirming the occurrence of serious adverse events, notifying the sponsor of a serious breach, maintenance of the clinical trial agreement, etc.

Research Misconduct & Fraud

What is research misconduct and fraud?

The Medical Research Council (MRC) definition of misconduct and fraud (or a variation of the MRC code) is widely used. This code states the following definition:

‘The fabrication, falsification, plagiarism or deception in proposing, carrying out or reporting results of research or deliberate, dangerous or negligent deviations from accepted practices in carrying out research. It includes failure to follow established protocols if this failure results in unreasonable risk or harm to humans, other vertebrates or the environment and facilitating of misconduct in research by collusion in, or concealment of, such actions by others. It also includes intentional, unauthorised use, disclosure or removal of, or damage to, research-related property of another, including apparatus, materials, writings or devices used in or produced by the conduct of research. It does not include honest error or honest differences in the design, execution, interpretation or judgement in evaluating research methods or results or misconduct unrelated to the research process. Similarly it does not include poor research unless this encompasses the “intention to deceive” (MRC, 1997).’

Some examples include:

  • Deliberately fabrication of laboratory analysis
  • Submitting the signature sheet for ethics from a different study
  • Recruiting and consenting patients without ethics approval
  • Conducting an equipment trial without MDA approval
  • Failure to document consent appropriately – e.g. consenting the patient whilst they are still anaesthetised
  • Gifted authorship on publications

The Medicine for Human Use (Clinical Trial) Regulations 2004 enacting the European Directive on Clinical Trials in the UK, lays down certain legal requirements and restrictions for the conduct of such trials. It would be considered research misconduct if these regulations or restrictions were breached.

Detecting research misconduct and fraud

Research misconduct and fraud is usually very difficult to detect and although organisations have monitoring and audit procedures these are unlikely to be fool proof in identifying deliberate fraudulent acts.

Research project steering groups, Trial Steering Committee and Trial Management Groups should be set up for each project as appropriate, and these should have Terms of References that include research misconduct and fraud.

Finally, the Medicines and Healthcare Products Regulatory Agency (MHRA) has the power of inspection of sites involved in the conduct of clinical trials of medicinal product, and may identify alleged research misconduct or fraud.

Whistle blowing is also an important route of notification. Most organisations have a raising concerns at work policy and this should be referred to where allegations of research misconduct or fraud arise, particularly from sources wishing to maintain anonymity. Normally, in these cases, the organisation will take all reasonable measures to protect the confidentiality of the member of staff raising bona fide concerns and to ensure that they suffer no detriment as a result.

Most organisations have a complaints procedure, and the R&D Office can link into the identification and investigation of any complaints that are research related.

Financial Policies and Conflicting Interests All researchers are asked on the IRAS research application forms to declare any interests they may have, including commercial interests/income, other research grants, other income. Institutions will have clear policies covering the receipt of such income or potentially competing interests. There may be a Counter Fraud Specialist within the organisation that the R&D Office can liaise with.

Preventing research misconduct and fraud

The organisation’s procedures for monitoring and auditing research will act as some deterrent.

However, an important element in an organisation’s approach to research misconduct and fraud is the setting up and dissemination of clear operational policies and procedures for research.

This section of the website clearly describes the key requirements for undertaking and being involved with research.  Keeping in place appropriate supervision may also help to reduce instances of malpractice and research misconduct or fraud.

Investigating research misconduct and fraud

The allegation will be dealt with in a timely manner, and in accordance with the organisation’s disciplinary procedures.