Posted: January 29th, 2023

Ethics and Governance Arrangement in Safety Reporting
Definitions

Course: Health Sciences and Medicine
Ethics and governance are critical considerations when submitting a protocol for a clinical trial or research study. This includes the ethical considerations that need to be taken into account when developing the protocol, as well as the governance arrangements that need to be put in place to ensure that the study is conducted in a responsible and ethical manner.
When submitting a protocol, it is important to consider the ethical implications of the study design and the potential impact on the study participants. This may include ethical considerations related to informed consent, privacy and confidentiality, risk to participants, and the potential for harm. It is also important to consider ethical issues related to the use of placebo treatments, the use of vulnerable populations, and the potential impact of the study on the wider community.
In addition to these ethical considerations, it is also important to consider the governance arrangements that will be in place during the study. This may include the appointment of an independent ethics committee to oversee the study, the appointment of a Data Safety Monitoring Board to monitor participant safety, and the development of a robust adverse event reporting system.
When amendments to the protocol are needed, it is important to ensure that these changes are made in a responsible and ethical manner. This may involve updating the informed consent process, modifying the study design to reduce risk to participants, or making changes to the governance arrangements to ensure that the study is being conducted in a safe and ethical manner.
Finally, when handling safety reporting and end-of-study reporting, it is important to ensure that the study is conducted in accordance with the governance arrangements that have been put in place. This may include regular safety monitoring and reporting to the independent ethics committee and the Data Safety Monitoring Board, as well as regular reporting of adverse events to the regulatory authorities.
The ethics and governance arrangements that need to be considered when submitting a protocol, making amendments, and handling safety reporting are critical considerations in the conduct of a clinical trial or research study. Ensuring that these arrangements are in place and followed will help to ensure that the study is conducted in a responsible and ethical manner, and that the safety and welfare of the study participants is protected.Ethics and Governance Arrangement in Safety Reporting
Definitions
Definition of Research
Research refers to an attempt to develop generalizable new knowledge by answering a number of clearly defined questions through systematic and rigorous methods (Woolham 2011, p.4). The preceding definition is broadened to cover even enquiries from most forms of disciplines. Research governance deals with both clinical and non-clinical research. Research is very important step in discovering empirical, qualitative and other forms of relationships between different variables under the study. Solutions for many disturbing health situations are sourced from research findings.
Definition of Research Governance
Research governance, as defined by Woolham (2011, p.3), is an arrangement that safeguards and protects research participants, researchers and investigators through the provision of a clear framework under which they carry out their research, enhances scientific and ethical quality, mitigates risks, monitors and promotes practice and performance.
All researches must be undertaken safely and under the strict guidance of the highest quality standards. As a result, research governance sets out policies and regulations to ensure that every research complies with the principles set out in the Research Governance Framework for Health and Social Care. Meanwhile, very much emphasis is reasonably laid on compliance with standards of good practices while the individual researchers’ freedom is not stringently restricted with the intent of flourishing good ideas that improve health care (Woolham 2011, p. 3).
Definition of Ethics
Ethics is a set of moral principles governing conduct of the research participants at all the stages of the research including data collection and analysis, writing and reporting. Ethics ensure that research participants are accorded dignity, well-being and safety. Ethical principles differ from their legal counterparts in that they question the morality of various actions of research participants throughout the research stages (Woolham 2011, p. 3).
Definitions of Amendments
Amendments imply changes that are made to a research upon the reception of the approval by the review body. In the following sections, this work will lay out the various requirements of the review body and its guidance in effecting the two types of amendments. Unless called for in cases of safety measures, only amendments that have been approved by the review body can be implemented (Field & Berman 2004).
Additionally, all researches sponsored by the OUH are subject to R&D team’s review and approval before they can be submitted to the regulatory bodies. The aforementioned action is taken to ensure that the changes effected do not affected indemnity (Sanders 2000, p. 19).
Substantial amendments
Substantial amendments are changes to the terms of the protocol or other documentation that significantly affects:
• The scientific values of the research
• The management of the research
• All aspects of participant’s integrity such as physical, mental and safety
• The quality and safety of a medicinal research
Examples of substantial amendments: The situations that change the management of the research are exemplified in the appointment of a new Principal Investigator at an already existing trial site or in the addition of new trial sites in CTIMP. Additionally, changes in the design methodology, background information and procedures affect the quality of the research. On one hand, the risk assessment benefit of the research can be greatly affected by the changes related to mental and physical integrity and safety of the participant while on the other the changes in documentation and sponsors have a much broader impact than can be imagined superficially (Annas 2003, p.1488).
Non-substantial amendments
The sponsor should be notified of non-substantial amendments that affect indemnity. They, however, do not require the approval of the HRA, REC and MHRA. The only requirement of non-substantial amendment is that the changes be kept in a Clinical Trail Master File.
Examples of Non-substantial amendments include:
• Minor changes effected on the protocols such as update of contact points, sponsor contacts, error correction and minor clarifications
• Updating the investigator’s brochure
• Minor alterations to the Chief Investigator’s research team at particular trial sites
• Flexes in the funding arrangements
• Changes in the arrangement for logistics for sample transportation and storage
• Inclusion of new investigators other than CTIMPs and new sites, and;
• Extension of the period of research
Submission of an Amendment
Sometimes it is necessary to amend various aspect of research projects such a updating the investigators brochures, new site additions, protocol changes, changing personnel in the study and many more. Sponsors and researchers must communicate these changes to the HREC.
The Review Process
A large portion of the amendments to the research do not require to be immediately reviewed by the HREC at the meetings or submission by a specified tight deadline. As a consequence, they are reviewed out of the session. Where necessary, the amendments to the research are sent to an approved ethics and scientific spokesman for the projects to determine whether the amendment can be approved or whether more details are needed. The ethic and scientific spokesman is required by law to be a member of the HREC. Should the amendment requires detailed consideration, the issue will be listed for discussion at the forthcoming meeting of the HREC (Karlberg & Speers 2010, p105).
Guidelines for Formulating General Amendments
The guidelines as outlined below include documents for commonly effected amendments submissions. Amendments to research are each unique and thus have different requirements. Significant differences will be seen in multisite and commercially sponsored projects or in projects that use ionization radiation (Abernethy, Shelby-James, Fazekas, Woods & Currow 2005, p.2). The documents that appropriate for specific amendments are confirmed and information about the ones which are not required is put in the amendments form. The following are the general requirements for amendments formulation:
All amendments to a research must be emailed to the HREC.
• All tracked and clean copies of the documents to which changes are made must be submitted together with the amendment.
• All documents which are new to the HREC should be accompanied with a statement alongside the amendment form.
• All study protocols must contain updated information regarding all research processes such as consent, recruitment and research procedures. In case the amendment process is deemed to change the aforementioned study processes, updated protocols must be submitted to the committee. This effectively ensures any new investigators to take on the latest protocol and carry out an approved protocol.
• The correctness of the approval is ensured by accurately and carefully listing the documents submitted on the amendment form. These documents are used to generate the approval letter.
• In case updates occur in the Participant Information and consent Form, the new wording should be in a lay language.
Examples of Amendments That Have Been Rejected By the Ethics Committee
European Data Protection Regulation
According to Robinson, Graux, Botterman and Valeri (2009, p.5), the amendment to the European data protection policy was reviewed and rejected by the European Union Committee. It was proposed by the European parliament in late January 2014. After reviewing the proposed amendments to the European data protection regulation at the commissioners’ of European Privacy and Data Protection Conference at Edinburgh from 23 to 24 April 2009, the commissioners ruled out the proposed amendments. The commission found out that the directive could not suffice in the long-run because the world’s society is constantly becoming globally networked. While the proposed amendment to the European data protection regulation contained plausible principles, they would have been only useful in the front-end but would have later required to be supported in order to meet the demands. More value could still be extracted from the arrangements that already existed through a better implementation of the current regulations. For example, a consensus could be established over the interpretation of various principles to shift the emphasis on the interpretation of others (Robinson, Graux, Botterman & Valeri 2009, p.5). The committee continued to underscore that abandoning the directive as it was not the best option because the directive had served, continued to serve and was the basis of taking data protection seriously.
Submission of Progress and Final Report
The principal investigator must submit the progress report to the Melbourne Health Human Research Ethics Committee in order that the project be approved. The principal Investigator is required to submit to the Committee the final report upon the completion date of the project or before the completion dates for projects that may be prematurely aborted (Emanuel, Wendler & Grady 2000, p. 2710).
Definition of Completion of a Project
Different projects have different sign posts signaling their completion. The different project types include: commercially sponsored clinical trials; investor initiated clinical trial and among others.
Firstly, commercially sponsored clinical trials is complete upon the execution of the closeout visit. Secondly, investor initiated clinical trials are complete upon the complete of the follow-up to the last patient and analysis of the associated data. Lastly, other forms of projects are complete upon the completion of the data collection process, a point where there is no further contact being made with patients, no access to medical records and personal health records and all the associated data have been analyzed.
Ongoing HREC Project Approval
Continued ethical approved is pegged on the reception of progress report by the Office for Research before the anniversary of approval by HREC. Should the investigator fail to do so, the project may be withdrawn from ethical approval (Karlberg & Speers 2010, p88).
Project Reporting Period
The reporting is done twelve months after the anniversary of the approval date. This implies that the first report is done after 11 months and then the subsequent reports are done at 12 months interval. For example, supposing a project was approved on 10th February 2012, the progress report for the first year would be for the period between February 2012 and January 2013, then January 2013 and January 2014. These dates must be noted at the top of the form.
Acknowledgement of Report Submission and Approval
The reception of projects is acknowledged through an auto-generated email response. The recipients are required to file the auto-generated response with other file containing information about the project site as evidence of reception of the progress report by the Office for Research. It also indicates that the on-going HREC approval will last for a further 12 months (Hays, S.J., Murphy, G. and Sinclair, N., 2003, p.187).
Audit of Project Reports
Taking an audit of a project is the only sure way through which RMH ensures that any research conducted within the realms of it auspices is adherent to the good clinical practices and ethical guidelines. Besides, auditing of project reports serves as an educative activity that is very helpful in streamlining and improving project procedures.
Deviations From and Violation of Protocol
Definitions of Project Deviations:
Deviations from protocols imply changes or departure from an originally intended project design and procedures under the control of investigator especially if it has not been approved by the ethics committee.
Although it is not mandatory to report to the HREC minor deviations that do not pose significant ethical consequences to the project and its users, they have to be recorded in the study file in addition to reporting them to the project sponsor.
Definitions of Protocol Violation:
Violations of project protocols imply changes or departure from an originally intended design or procedure of the research protocol which impacts the rights, well-being and safety of the participants and the reliability, accuracy and completeness of the study data.
Conversely, major deviation and violation of project protocols have a higher risk to the safety of the patient and substantial ethical and administrative ramification and must therefore be reported to the HREC and the sponsor immediately they are noticed.
Safety Reporting and Study Completion
Safety Reporting
It is the duty of the project sponsors to compile lists of cases suspected to bear high risks to the human subjects with regard to clinical trials annually. In addition to compiling annual reports, sponsors are supposed to submit such report to the relevant Ethics Committees (Ioannidis and Lau 2002, p.79). These reports should detail the safety measures for the human subjects and national coordinators such as the person responsible for the study. Accordingly, they should offer their opinions on the suspected cases.
Completion of the Study
Within 90 days upon the completion of the study, the investigators and the sponsors must notify the relevant ethics committee of status of the clinical trial on medical products. In case the trail are discontinued prematurely, the reasons for that course along with the project completion status must be submitted to the ethics committee within 15 days (Abernethy, Shelby-James, Fazekas, Woods & Currow 2005, p8). There are specification forms through which then end of a project can be done.

Ethical Philosophies for Medical Research Involving Human Beings
Medical research involving human subjects must, by all means, be strictly compliant to the prescribed scientific principles such as being based on a sound knowledge of scientific literature, relevant information sources, satisfactory laboratory and prior animal experimentation where applicable. The medical staff to conduct a medical research must have all the relevant scientific and clinical qualifications which are proven. This effective ensures that the responsibility for the human subjects rests with highly qualified medical staff even after the consent of the human subject has been obtained (Eckstein 2003, p.145).
It is also required of a medical research physicians to protect and safeguard the life and health, dignity, well-being and privacy of the human subjects involved (Eckstein 2003, p.145). Additionally, any medical research involving human subjects must only be conducted should its medical benefits outweigh its potential risk, the subjects must be informed volunteers and the protocol should be clearly formulated in accordance with all the scientific and clinical requirements, governance and review of the ethics committee and must contain a statement indicating that ethical considerations involved in the study have been met in compliance with the requirement of the ethics committee.
Special Requirements for Clinical Trials Involving DNA Samples
The ethics committee requires that a separate consent form for DNA be included. The consent form details such as elaborate information about the DNA samples, the content of the information the human subject can be given on his DNA sample, the data will be managed and how the DNA sample will be stored. It is the general recommendations of the Committees, for example of the Finland’s to store the samples locally except for the cases where they are sent abroad for analysis (Roden et al. 2008, p.362). The samples can be sent abroad to avoid gathering of the data in the DNA sample banks. As a special requirement, the DNA samples are usually given pseudo-names and coded before sending them abroad to ensure maximum donor anonymity.
Issues and Challenges
There are many challenging issues with which the organizations reviewing ethics and governance policies are faced. While many are in consensus that these challenges are uniquely manifested in the individual organizations, mot are common among the said agencies.
The Extent of Regulation
Many concerned researcher are questioning how far must the agencies go in regulating ethics and governance arrangements in formulation, submission and reporting research. With the fear of a possibility of ethics creep setting in, Haggerty (2004, p.394) warned against supporting and flourishing regulatory agencies that constrain freedom for academic and scholarly activity. Thee school of thoughts is a constant reminder to us that we need vigilance because the impetus to develop ethic and governance systems are based on mere guidance and not regulations. Moreover, there are presently no performance sign posts through which the universities, the NHS and the councils may be held accountable for their ethics and governance review systems (Woolham 2011, p. 20). There are only a couple of researches who emphasize on the significance of such reviews in directions that maybe unwelcomed by other researcher. Such complaints comprise the inconsistency of decision making by the ethics committee.

Proportionality
It is agreeable that research should be scrutinized for their proportionality to the degree of risk in principle. Nonetheless, the practical achievement of these proportionality has been a nightmare amongst researchers (Woolham 2011, p.23). Majority of researchers dismiss the exiting ethics and governance arrangement as being appropriate only for clinical research. Dingwall (2006) expressed this in a rather pungent tone when he suggested they (researchers) should not be treated as though they were going to forcibly inject dependent patients with some sort of an irreversible toxic substance (p.54).
Inexperienced Researchers and Students
Different universities have different policies regarding allowing students to conduct non-desk based research involving ‘live subjects’. Although some universities may offer such learning opportunities to students there are strong counter arguments (Black & Donald 2001, p.276). Foremost among the counter arguments, is the need to protect vulnerable patients from the clumsy questions and the concerns that the ongoing research may not add meaningful knowledge to the topic under investigation. Secondly, the opponents of this premise argue that students should seek an independent ethic and governance review of their study. Lastly, the timescale for the students project completion is too short to allow for amendments should they be required after a review. As a consequence, many universities current discourage allowing undergraduates from carrying out ‘live’ especially in healthcare (Woolham 2011, p. 24).
In conclusion, ethics and governance requirements for clinical research processes such as data collection, report compilation, reporting, amendments and auditing are very important in ensuring that research projects are conducted in accordance with the set standards of quality. Research ethics and governance serve to uphold quality, well-being, safety and health of participants of a research. Although non-substantial amendments may intentionally slip the table of the ethics committee, the committee must be notified of any substantial amendments for approval. The proposed amendments must be submitted to the ethics committee to be review to determine whether the amendments are approvable or not. This done by the ethics spokesman. The amendments must be formulated under strict guidance of the set regulations. The approval of amendments are subject to the timely submission of both progress and final project reports. Continued ethical approved is pegged on the reception of progress report by the Office for Research before the anniversary of approval by HREC. The reporting is done twelve months after the anniversary of the approval date. Medical research involving human subjects must be strictly compliant to the prescribed scientific principles such as being based on a sound knowledge of scientific literature, relevant information sources, satisfactory laboratory and prior animal experimentation where applicable. The ethics committee requires that a separate consent form for DNA be included among other emerging issues in safety reporting.

References
Abernethy, A.P., Shelby-James, T., Fazekas, B.S., Woods, D. and Currow, D.C., 2005. The Australia-modified Karnofsky Performance Status (AKPS) scale: a revised scale for contemporary palliative care clinical practice [ISRCTN81117481]. BMC palliative care, 4(1), p.1.
Annas, G.J., 2003. HIPAA regulations-a new era of medical-record privacy? New England Journal of Medicine, 348(15), pp.1486-1490.
Black, N. and Donald, A., 2001. Evidence based policy: proceed with care Commentary: research must be taken seriously. Bmj, 323(7307), pp.275-279.
Dingwall, R., 2006. Confronting the Ant-Democrats: the unethical nature of ethical regulation in social science. Medical Sociology Online (1) pp51-58.
Eckstein, S., 2003. Manual for Research Ethics Committees: Centre of Medical Law and Ethics, King’s College London. Cambridge University Press.
Emanuel, E.J., Wendler, D. and Grady, C., 2000. What makes clinical research ethical? Jama, 283(20), pp.2701-2711.
Field, M.J. and Berman, R.E. eds., 2004. The ethical conduct of clinical research involving children. National Academies Press.
Haggerty, K.D., 2004. Ethics creep: Governing social science research in the name of ethics. Qualitative sociology, 27(4), pp.391-414.
Hays, S.J., Murphy, G. and Sinclair, N., 2003. Gaining ethical approval for research into sensitive topics: ‘two strikes and you’re out?’1. British Journal of Learning Disabilities, 31(4), pp.181-189.
Ioannidis, J.P. and Lau, J., 2002. Improving safety reporting from randomised trials. Drug safety, 25(2), pp.77-84.
Jaretzki, A.I.I.I., Barohn, R.J., Ernstoff, R.M., Kaminski, H.J., Keesey, J.C., Penn, A.S. and Sanders, D.B., 2000. Myasthenia gravis Recommendations for clinical research standards. Neurology, 55(1), pp.16-23.
Karlberg, J.P.E. and Speers, M.A. eds., 2010. Reviewing clinical trials: a guide for the ethics committee. Clinical Trials Centre.
Robinson, N., Graux, H., Botterman, M. and Valeri, L., 2009. Review of eu data protection directive: summary. Information Commissioner’s Office.
Roden, D.M., Pulley, J.M., Basford, M.A., Bernard, G.R., Clayton, E.W., Balser, J.R. and Masys, D.R., 2008. Development of a large‐scale de‐identified DNA biobank to enable personalized medicine. Clinical Pharmacology & Therapeutics, 84(3), pp.362-369.
Woolham, J., 2011. Research governance and ethics for adult social care research: procedures, practices and challenges.

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