A close and effective monitoring is required to assess the risks associated with the use of medicines. In fact adverse effects, interactions with foods or with other medicines and risk factors are to be noticed only during its real use over the years.
- 1 What is the importance of safety monitoring of the drug?
- 2 What is pharmacovigilance monitoring of drug safety?
- 3 What is the importance of clinical monitoring?
- 4 Who monitors drug safety and clinical trials?
- 5 What does FDA post market drug safety monitoring mean?
What is the importance of safety monitoring of the drug?
2.2. Communicating Safety Information among Stakeholders – Timely communication among the various stakeholders is critical to ensure subject safety in clinical trials. Sponsors of clinical trials are accountable for monitoring the subjects appropriately, including the requirement of long-term follow up as appropriate.
- The protocol (including the ICF) specifies the details of the assessments, the frequency and the length of follow-up.
- In addition, most pharmaceutical sponsors have Standard Operating Procedures (SOPs) in place to collect, process, review, evaluate, report and communicate accumulating safety data to ensure a systematic approach for safety surveillance and monitoring.
In general, safety information, including adverse events and laboratory findings are reported to a sponsor by investigators conducting the clinical trial. However, safety information may come from sources outside the immediate clinical trial. The sponsor is required to promptly review all information relevant to the safety of the drug and to update subjects, investigators, IRBs and regulatory authorities of any new risks associated with the use of the investigational drug that arise from the clinical trial or from other sources.
Amending the clinical trial protocol is one way to implement procedural changes that are necessary given the updated safety information. Another way to communicate the evolving safety information is through the periodic update of the Investigator’s Brochure (IB). The IB is a compilation of the clinical and non-clinical data on the investigational drug that are relevant to the study of the drug in human subjects.
Its purpose is to provide the investigators and others involved in the trial with the information to facilitate their understanding of the rationale for and their compliance with many key features of the protocol, such as the dose, dose frequency/interval, methods of administration and safety monitoring procedures,
The IB should be reviewed at least annually and revised as necessary in compliance with the sponsor’s written procedures and the local requirements. A new safety finding that represents a significant risk to study subjects should be communicated to the investigators immediately, along with an update to the IB and possibly to the protocol and the ICF.
For trials where DSMBs are in place, sponsors should also communicate significant safety findings to the DSMBs employed to oversee clinical trials of the same or similar investigational drug(s). In other situations, DSMBs may be in possession of critical safety information and they will need to follow the DSMB charter and the protocol to make recommendations to the sponsor with regard to its safety findings and whether the trial should continue as planned.
- The goal of safety monitoring in clinical trials is to identify, evaluate, minimize and appropriately manage risks.
- In Europe, Risk Management Plans (RMPs) are required by the EMA as part of the drug approval process.
- An RMP includes a summary of important identified risks of the drug, potential risks and missing information, which serves as the basis for an action plan for pharmacovigilance and risk minimization activities.
The CIOMS VI working group recommended establishing a multidisciplinary Safety Management Team (SMT) within the sponsor organization to be in charge of safety surveillance and decision making on risk management and minimization activities. The SMT is responsible for coordinating all safety-related activities involving quantitative assessment of risks, signal detection and identification of adverse events of special interest (AESIs).
- For trials in earlier stages without DSMBs, sponsors may choose to appoint an internal multi-functional data review team removed from the direct day-to-day trial operations related to the investigational drug to perform ongoing review of the safety data.
- This independent data review team is empowered to perform similar functions as the DSMB on later stage trials.
The CIOMS VI working group endorsed the use of the Development Core Safety Information (DCSI) as the summary of the identified safety issues for an investigational drug. DCSI was recommended to be a part of the IB that defines the list of suspected adverse reactions.
- Safety issues or adverse drug reactions contained in this document should be considered “expected” for regulatory reporting purposes.
- Only suspected adverse drug reactions that are both serious and unexpected are subject to expedited case reporting to regulatory authorities in either seven (fatal or life-threatening) or 15 calendar days.
Slightly different terminologies exist, including Suspected Unexpected Serious Drug Reaction (SUSAR) or Serious Unexpected Suspected Drug Reaction, Contrary to the routine expedited case reporting to regulatory authorities, the CIOMS VI working group recommended sponsors provide periodic updates of the evolving benefit/risk profile and highlight important new safety information to the participating investigators and IRBs.
However, in some regions, expedited case reporting to investigators and IRBs are still required by local regulations. Regulatory authorities also require reporting of safety information in the aggregate rather than the individual cases. In the US, the FDA IND regulations require annual IND reports, which include aggregate safety information across the entire development program of an investigational drug.
CIOMS VI working group recommended defining a single Development Safety Update Report (DSUR) for submission to regulators on an annual basis. For submission of New Drug Applications (NDAs), sponsors aggregate safety information from all relevant trials of the drug to perform integrated safety analyses in support of the filing for marketing authorization.
The common data structure using SDTM (Standard Data Tabulation Model) defined by Clinical Data Interchange Standards Consortium (CDISC) has greatly facilitated the safety data integration and analyses. It also enables sponsors to build a safety data warehouse to better respond to safety related queries across the entire drug program.
Proactive early planning of safety analyses in a Program Safety Analysis Plan (PSAP) and periodic aggregate safety analyses have been recommended as standard industry practices, The PSAP is a living document that will form the basis for integrated safety analyses in an NDA.
What is the meaning of drug safety monitoring?
Drug safety monitoring is a risk mitigation exercise in which the ADRs caused by therapeutic drugs, biologicals or devices can explored, prevented or minimized.
What is pharmacovigilance monitoring of drug safety?
Pharmacovigilance is the process and science of monitoring the safety of medicines and taking action to reduce the risks and increase the benefits of medicines. It is a key public health function. The EU pharmacovigilance system is one of the most advanced and comprehensive in the world and represents a robust and transparent instrument to ensure a high level of public health protection throughout the EU.
What is the role of pharmacovigilance in safety monitoring in clinical trials?
Pharmacovigilance analyse which adverse events cross the line of drug’s efficacy. Or in other words we can say it determines which side effects are worth the risk to patients compared with how effective they are at treating a disease.
What is the purpose of medication monitoring?
Monitoring Methods – Through our rigorous monitoring methods, clients receive support and are held accountable when taking their medication. Our medication monitoring program includes: Comprehensive Testing As a result of our detection capabilities and testing methods, medication monitoring can highlight the use of prescription medications and illicit drugs.
- The goal of medication monitoring is to ensure that prescription medication levels remain therapeutic and that no other illicit drugs are ingested,
- Based on the individual needs of a client, as well as their recovery goals, we can test for different medications.
- Emphasis may be placed on the areas that will have the greatest effect on the individual.
Drug Abuse and Misuse Detection The potential for opiate addiction is severe, but opiates are still prescribed to patients for various reasons, often to deal with chronic pain. In order to combat the harmful potential of prescription opiates and other drugs, medication monitoring helps identify signs of misuse and abuse before they spiral out of control.
What is the importance of clinical monitoring?
What is the purpose of clinical trial monitoring? 1 MRC Clinical Trials Unit at UCL, 90 High Holborn, London, WC1V 6LJ UK Find articles by 1 MRC Clinical Trials Unit at UCL, 90 High Holborn, London, WC1V 6LJ UK Find articles by 2 Bristol Trials Centre (BTC), BRI Hub (CTEU Bristol), Level 7 Queens Building, Bristol Royal Infirmary, Marlborough Street, Bristol, BS2 8HW UK Find articles by 3 Nottingham Clinical Trials Unit, University of Nottingham, Building 42, University Park, Nottingham, NG7 2RD UK Find articles by 4 NHS Blood and Transplant Clinical Trials Unit, Long Road, Cambridge, CB2 0PT UK Find articles by 5 Clinical Trials Research Unit, ScHARR, The University of Sheffield, Regent Court, 30 Regent Street, Sheffield, S1 4DA UK Find articles by 6 Department of Surgery & Cancer, Imperial College London, Hammersmith Campus, 1st Floor, ICTEM Building, Du Cane Road, London, W12 0NN UK Find articles by 7 Centre for Trials Research, College of Biomedical & Life Sciences, Cardiff University, 6th Floor, Neuadd Meirionnydd, Heath Park, Cardiff, CF14 4YS UK Find articles by 8 Health Research Board – Trials Methodology Research Network, NUI Galway, University Road, Galway, Ireland Find articles by 9 ICR-CTSU, 15 Cotswold Road, Belmont, Sutton, Surrey, SM2 5NG UK Find articles by 10 Norwich Clinical Trials Unit, Norwich Medical School, University of East Anglia, Norwich, NR4 7TJ UK Find articles by 11 Centre for Trials Research, College of Biomedical & Life Sciences, Cardiff University, 7th Floor, Neuadd Meirionnydd, Heath Park, Cardiff, CF14 4YS UK Find articles by 3 Nottingham Clinical Trials Unit, University of Nottingham, Building 42, University Park, Nottingham, NG7 2RD UK Find articles by
- 1 MRC Clinical Trials Unit at UCL, 90 High Holborn, London, WC1V 6LJ UK
- 2 Bristol Trials Centre (BTC), BRI Hub (CTEU Bristol), Level 7 Queens Building, Bristol Royal Infirmary, Marlborough Street, Bristol, BS2 8HW UK
- 3 Nottingham Clinical Trials Unit, University of Nottingham, Building 42, University Park, Nottingham, NG7 2RD UK
- 4 NHS Blood and Transplant Clinical Trials Unit, Long Road, Cambridge, CB2 0PT UK
- 5 Clinical Trials Research Unit, ScHARR, The University of Sheffield, Regent Court, 30 Regent Street, Sheffield, S1 4DA UK
- 6 Department of Surgery & Cancer, Imperial College London, Hammersmith Campus, 1st Floor, ICTEM Building, Du Cane Road, London, W12 0NN UK
- 7 Centre for Trials Research, College of Biomedical & Life Sciences, Cardiff University, 6th Floor, Neuadd Meirionnydd, Heath Park, Cardiff, CF14 4YS UK
- 8 Health Research Board – Trials Methodology Research Network, NUI Galway, University Road, Galway, Ireland
- 9 ICR-CTSU, 15 Cotswold Road, Belmont, Sutton, Surrey, SM2 5NG UK
- 10 Norwich Clinical Trials Unit, Norwich Medical School, University of East Anglia, Norwich, NR4 7TJ UK
- 11 Centre for Trials Research, College of Biomedical & Life Sciences, Cardiff University, 7th Floor, Neuadd Meirionnydd, Heath Park, Cardiff, CF14 4YS UK
Sharon B. Love, Email:, Corresponding author. Received 2021 Dec 22; Accepted 2022 Sep 16. © The Author(s) 2022 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.
The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
To view a copy of this licence, visit, The Creative Commons Public Domain Dedication waiver () applies to the data made available in this article, unless otherwise stated in a credit line to the data. The sources of information on clinical trial monitoring do not give information in an accessible language and do not give detailed guidance.
- In order to enable communication and to build clinical trial monitoring tools on a strong easily communicated foundation, we identified the need to define monitoring in accessible language.
- In a three-step process, the material from sources that describe clinical trial monitoring were synthesised into principles of monitoring.
A poll regarding their applicability was run at a UK national academic clinical trials monitoring meeting. The process derived 5 key principles of monitoring: keeping participants safe and respecting their rights, having data we can trust, making sure the trial is being run as it was meant to be, improving the way the trial is run and preventing problems before they happen.
From the many sources mentioning monitoring of clinical trials, the purpose of monitoring can be summarised simply as 5 principles. These principles, given in accessible language, should form a firm basis for discussion of monitoring of clinical trials. The online version contains supplementary material available at 10.1186/s13063-022-06763-2.
Keywords: Clinical trial monitoring, Trial conduct, Clinical trials methodology The MRC-NIHR Trials Methodology Research Partnership (TMRP) Trial Conduct Working Group Data Quality and Monitoring (DQM) subgroup (hereafter “TMRP DQM”) comprises 13 people (authors of this paper) interested in improving the monitoring of clinical trials (four researchers, six trial managers, three other).
Though location was not an exclusion when applications were requested for this subgroup, the current members are those involved in academic trials from the UK and Ireland, each involved in a variety of national and international trials. Despite each adapting our way of working from the guidance available, it was clear that we did not have a common monitoring strategy or understanding of terminology.
We identified the need to go back to basics and define the purpose of monitoring. This will enable communication between researchers, regulators and trial teams and will give a strong easily explained foundation on which to build tools for clinical trial monitoring.
- The purposes of trial monitoring are to verify that:
- (a) The rights and well-being of human subjects are protected.
- (b) The reported trial data are accurate, complete, and verifiable from source documents.
- (c) The conduct of the trial is in compliance with the currently approved protocol/amendment(s), with GCP, and with the applicable regulatory requirement(s).”
Though ICH GCP has used this underlying definition of the purpose of monitoring since 1996, it is not written in accessible language and does not contain any explicit detailed guidance on monitoring activities, Therefore, each clinical trial sponsor has taken this definition or the one in their own country’s legislation (for example ), interpreted it and created their own monitoring activities.
This has led to wide variation in practices, as noted in several surveys of monitoring approaches, Despite the recent shift towards a more risk-based approach, which has led to a re-focusing on monitoring, there remains little detailed guidance available on how it should be done. To facilitate the development of any guidance in the future, a clear understanding of the purpose of monitoring is essential.
This paper describes the process whereby the MRC-NIHR TMRP DQM extracted the purpose of monitoring, as described by pertinent sources, and from them defined the purpose of monitoring in accessible language. We hope that this paper can be used to formulate detailed guidance on how to monitor clinical trials.
- We chose the sources from guidance provided by organisations that any one of the TMRP DQM referred to when deciding how to run trials.
- Table gives the organisations included and their aims.
- Each author reviewed an organisation’s publicly available online or downloadable information to extract any material on the purpose of monitoring.
We did not contact the organisations. The documents reviewed included guidance documents, minutes of workshops, toolkits, blogs and reports of questions and answers (Additional file ). In a second round, the information related to the purpose of monitoring was distilled into non-repetitive statements by pairs of authors.
|Organisation and URL||Short name||Description|
|Clinical Trials Transformation Initiative||CTTI||
|European Medicines Agency||EMA||The European Medicines Agency (EMA) is a decentralised agency of the European Union (EU) responsible for the scientific evaluation, supervision and safety monitoring of medicines in the EU. Public body, European Union|
|US Food and Drug Administration||FDA||The Food and Drug Administration is responsible for protecting the public health by ensuring the safety, efficacy, and security of human and veterinary drugs, biological products, and medical devices; and by ensuring the safety of our nation’s food supply, cosmetics, and products that emit radiation. Public body, USA and further afield|
|Health Research Authority||HRA||vision is for high-quality health and social care research that improves people’s health and wellbeing, and core purpose is to protect and promote the interests of patients and the public in health and social care research. Public body, UK|
|International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use||ICH||Brings together the regulatory authorities and pharmaceutical industry to discuss scientific and technical aspects of drug registration. Private body, International|
|Medicines and Healthcare products Regulatory Agency||MHRA||Regulates medicines, medical devices and blood components for transfusion in the UK. Public body, UK|
|National Institute for Health Research||NIHR||The UK’s largest funder of health and care research and provide the people, facilities and technology that enables research to thrive. Working in partnership with the NHS, universities, local government, other research funders, patients and the public, deliver and enable world-class research that transforms people’s lives, promotes economic growth and advances science. Public body, UK|
|TransCelerate Biopharma Inc||Trans-Celerate||Aim to collaborate across the global biopharmaceutical research and development community to identify, prioritize, design and facilitate implementation of solutions designed to drive the efficient, effective and high-quality delivery of new medicines. USA based, international|
|UK Trial Manager Network||UKTMN||Aims to facilitate the development of a well-trained, highly motivated, effective workforce of trial managers within the UK health care system who will make an important contribution to the efficient delivery of high quality clinical trials. Private body, UK|
To obtain feedback on their value, we presented the five key principles covering the purpose of monitoring to delegates at the UKCRC Task and Finish Monitoring Group annual meeting 2021 (a national meeting of experts in conducting academic clinical trial monitoring in the UK) and asked “Are there any of these purposes of monitoring that you do not agree with?”, giving options to disagree with any principle or to answer “No, I agree with all 5 proposed principles”.
- In addition, delegates were asked to suggest any other potential “principles of monitoring” that we should consider (see Additional file ).
- We show the underlying text for these five principles and also give examples of which monitoring activities could happen within each of these principles.
- We also present the results of our poll of the annual meeting.
The results of our synthesis for the purpose of monitoring are given in Table and include five principles. The purpose of monitoring is keeping participants safe and respecting their rights, having data we can trust, making sure the trial is being run as it was meant to be, improving the way the trial is run and preventing problems before they happen.
|Purpose of monitoring|
|Key principles in lay terms||Key principles in more technical language|
|Keeping participants safe and respecting their rights||To ensure, enhance and protect participants’ safety, wellbeing and rights.|
|Having data we can trust||Having the systems and processes (such as source data verification) to ensure that each data item is as reliable as is needed to be sure of the results of the trial|
|Making sure the trial is run as it was meant to be||Maintain trial integrity by ensuring the trial is conducted in compliance with the currently approved protocol/documentation, with GCP and with the applicable regulatory requirements|
|Improving the way the trial is run||Improving quality, conduct and efficiency in clinical trials.|
|Preventing problems before they happen||Contingency and mitigation planning for risks to both participant safety and trial processes.|
Results from poll about the principles of monitoring at national meeting of those monitoring academic clinical trials in the UK
|Response to the question “Are there any of these that purposes of monitoring that you do not agree with?” from 93 respondents||N (%)|
|Keeping participants safe and respecting their rights||1 (1%)|
|Having data we can trust||2 (2%)|
|Making sure the trial was run as it was meant to be||3 (3%)|
|Improving the way the trial is run||8 (9%)|
|Preventing problems before they happen||4 (4%)|
|No – I agree with all 5 proposed principles||80 (86%)|
Table shows the clarification of our derivation of these principles by giving examples from the underlying sources. For example, the principle “having data we can trust” came in part from the CTTI statement “Ensuring that data quality is sufficient to answer study question”.
|Principle of monitoring in lay terms||Examples of principle source a||Source|
|Keeping participants safe and respecting their rights||Protecting the rights, safety, and welfare of subjects under the investigator’s care||FDA|
|The risk associated with the IMP should also determine the trial procedures for monitoring the safety of participants.||MHRA|
|Inspectors should verify procedures for reviewing and communicating findings that could adversely affect the safety of subjects.||EMA|
|safety must be monitored in all trials and therefore the need for formal procedures to cover early stopping for safety reasons should always be considered.||ICH E9 3.4|
|adequate oversight and monitoring during the trial will help ensure that trial subject safety is maintained throughout the trial.||NIHR|
|Having data we can trust||Careful attention to quality during trial planning, investigator training, trial monitoring and audit will help consistently achieve trial quality required.||ICH|
|Ensuring that data quality is sufficient to answer study question.||CTTI|
|Monitoring strategies, tailored to risks, should permit timely oversight and be focused on critical processes and critical data.||TransCelerate|
|Appropriate planning before the trial and adequate oversight and monitoring during the trial will help ensure that trial subject safety is maintained throughout the trial and that there is accurate reporting of results at its conclusion.||NIHR|
|Ensure data quality across sites.||FDA|
|Making sure the trial was run as it was meant to be||preventing or mitigating important and likely sources of error in the conduct, collection, and reporting of critical data and processes necessary for human subject protection and trial integrity.||FDA|
|perform checks that include: verification that trial documents exist, assessment of the site’s understanding of, and compliance with the protocol and trial procedures||NIHR|
|Essential documents are those ‘documents which individually and collectively permit evaluation of the conduct of a trial and the quality of the data produced’ and they serve to demonstrate compliance with the principles of GCP and regulatory requirements.||UKTMN|
|Investigators are appropriately selected, trained and supported to complete the proposed clinical trial (MHRA).||MHRA|
|Improving the way the trial is run||Monitoring during the trial will help ensure that trial subject safety is maintained throughout the trial and that there is accurate reporting of results at its conclusion.||NIHR|
|Monitoring strategies, tailored to risks, should permit timely oversight and be focused on Critical Processes and Critical Data. Notably, Investigators are responsible for their site’s data quality and are expected to partner with the Sponsor to address, resolve, and prevent issues.||TransCelerate|
|Chief investigators are responsible for the overall conduct of a research project including adhering to the agreed procedures and arrangements for reporting (e.g. progress reports, safety reports) and for monitoring the research, including its conduct, the participants’ safety and well-being and the ongoing suitability of the approved proposal or protocol in light of adverse events or other developments.||HRA|
|Moreover, a risk-based approach is dynamic, more readily facilitating continual improvement in trial conduct and oversight. For example, monitoring findings should be evaluated to determine whether additional actions (e.g. training of clinical investigator and site staff, clarification of protocol requirements) are necessary to ensure human subject protection and data quality across sites.||FDA|
|Maximizing efficiency for minimal resource use||CTTI|
|Preventing problems before they happen||Sponsors should prospectively identify critical data and processes, then perform a risk assessment to identify and understand the risks that could affect the collection of critical data or the performance of critical processes, and then develop a monitoring plan that focuses on the important and likely risks to critical data and processes.||FDA|
|A Trial Monitoring Plan will be developed and agreed by the Trial Management Group (TMG), TSC and CI based on the trial risk assessment which may include on site monitoring. This will be dependent on a documented risk assessment of the trial.||HRA|
|The sponsor should develop a monitoring plan that is tailored to the specific human subject protection and data integrity risks of the trial. The plan should describe the monitoring strategy, the monitoring responsibilities of all the parties involved, the various monitoring methods to be used, and the rationale for their use. The plan should also emphasize the monitoring of critical data and processes.||ICH|
|Once developed, the risk assessment and associated management/monitoring plans would form the basis of a common understanding by all stakeholders on the risks for that trial and facilitate a risk-proportionate approach to the trial activities.||MHRA|
|Risk-based monitoring: An adaptive approach that directs monitoring focus and activities to the evolving areas of greatest need which have the most potential to impact subject safety and data quality.||TransCelerate|
We have given examples in Table from sources and from our experience to show how each principle may be mitigated by monitoring. For example, if the principle of monitoring is to keep participants safe and respect their rights, then we should monitor to ensure the consent is valid. Examples of monitoring for each principle
|Keeping participants safe and respecting their rights||Ensure valid consent by checking the consent forms are completed correctly Ensure data available by checking that the expected data have been entered onto the database Look regularly at the amassed safety data and protocol compliance. Present to regulatory authorities, CI, DMC, TMG, REC and safety review committee and act upon their direction/advice. This may result in a change to the protocol or trial conduct.|
|Having data we can trust||
|Making sure the trial was run as it was meant to||Ensure site staff are appropriately trained and qualified to deliver their role on the trial and to follow trial specific procedures and processes (e.g. monitoring delegation and training logs, checking CVs). Collect and check protocol deviations/non-conformances and ensure systems are in place to mitigate risks of these happening again such as retraining and providing working practice documents. Ensure a monitoring plan is in place that allows timely evaluation of significant issues identified.|
|Improving the way the trial is run||
|Preventing problems before they happen||Base the monitoring plan and activities on a risk assessment Undertake a risk assessment to assess the potential risks and puts things in place to prevent and monitor these risks.|
We have clarified the purpose of monitoring in accessible language from pertinent sources. This will enable communication between those carrying out clinical trial monitoring and facilitate the building of clinical trial monitoring tools on a strong easily communicated foundation.
- Clinical trial monitoring is a crucial part of trial conduct, improving the safety of the participants, the quality of the data and the trial integrity.
- Clinical trial monitoring is conducted by monitors, quality assurance teams and by trial managers,
- Guidance on trial monitoring is spread amongst different sources within and between organisations, is often in technical language and does not describe practicalities of how to achieve the monitoring aims.
The differing specialities conducting monitoring and the disparity and high-level content of the sources mean there is scope for misunderstanding and communication errors. This could easily lead to poor quality monitoring which could jeopardise the protection of the rights and safety of patients and the data and trial integrity.
- Also, misunderstanding could lead to over-monitoring for no additional value, placing additional burden on research teams and sites and increasing the cost of undertaking research.
- It is difficult to have methodology research discussions, and therefore to deliver monitoring tools, without agreement of a common basis which multiple disciplines can all understand.
It is difficult for grant committees to understand the value of monitoring research when there is no easily understandable consensus on why we need to do good clinical trial monitoring. The differing language and range of ideas on clinical trial monitoring are confusing and unhelpful.
- The variability in language and practices this range has caused, as evidenced by 13 people in the UK who were experienced in clinical trial monitoring finding it difficult to communicate and find common ground, is limiting progress in clinical trial monitoring.
- We have synthesised the sources to describe the purpose of monitoring in five key principles described in both technical and lay language (Table ).
We intend this to be a basis for making monitoring more accessible. The purpose of monitoring principles presented in this paper are active, continual and responsive to monitoring findings. They are focussed on the conduct of a real trial rather than based on theory.
They are aimed at monitoring to intervene and make trials better rather than certifying what has already been done. Monitoring is an integral part of trial conduct rather than an add-on. Our first three principles link with parts a, b and c of the ICH definition of monitoring (see methods) but the idea of improving trials or preventing problems before they happen is not part of the ICH definition.
These are important aspects of monitoring, as finding an issue at one site early in the trial means that training can be given to the other sites and the overall trial is improved to the benefit of current and future patients. Stating improvement and prevention in our principles will help those running trials to address improvement to the trial and prevent poor conduct.
The FDA provided particularly valuable sources for this paper as they have strongly advocated risk-based monitoring and have had to be clear in their documents as they are extensively used worldwide. Supplementary Table lists the sources used. Although the thirteen authors all have experience of clinical trial monitoring in the UK and Irish academic setting, relevant and valuable sources of information may have been missed.
The first selection of useful text from the individual documents within each source was done by one author and the second phase by groups of two or three. Only the final phase was completed by all authors together. These are limitations in the study but it also exemplifies how those devising monitoring policies for their trials and those carrying out monitoring activities must refer to multiple sources.
- The 86% vote of agreement with the five principles at the UK monitoring meeting corroborates the work done.
- Though there is a limitation due to this work using world-wide English language sources, being led by UK and Ireland researchers and being corroborated in a UK national meeting, it is based on sources that are used by many.
In future, it would be good to extend this to more of the clinical trial monitoring community world-wide. Although building relationships with sites has been noted as a useful part of monitoring in publications, this did not come through from the sources reviewed and was only mentioned by one poll respondent at the national monitoring meeting.
At present, we do not note it as one of the main five principles but further work may add principles. As each group leading clinical trials has created their own monitoring strategy and language, there have been difficulties in communicating between groups, Our principles clarifying the purpose of monitoring should improve communication and enable the monitoring community to start producing clear monitoring practical guidelines and to start sharing tools.
These principles should be considered when undertaking risk assessments, developing monitoring plans and carrying out monitoring activities. From the many sources mentioning monitoring of clinical trials, the purpose of monitoring can be summarised simply as (i) keeping participants safe and respecting their rights, (ii) having data we can trust, (iii) making sure the trial is being run as it was meant to be, (iv) improving the way the trial is run and (v) preventing problems before they happen.
|COVID-19||Coronavirus disease 2019|
|CTTI||Clinical Trials Transformation Initiative|
|CTU||Clinical Trials Unit|
|EMA||European Medicines Agency|
|FDA||US Food and Drug Administration|
|GCP||Good Clinical Practice|
|HRA||UK Health Research Authority|
|ICH||International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use|
|MHRA||Medicines and Healthcare products Regulatory Agency|
|NIHR||National Institute for Health Research|
|UKTMN||UK Trial Managers Network|
All authors are members of the MRC-NIHR Trials Methodology Research Partnership Trial Conduct Working Group Data Quality and Monitoring subgroup. SBL and VYE were funded by MRC grant MC_UU_00004/08. LOS is funded by the Health Research Board-Trials Methodology Research Network grant (HRB-TMRN-2017-1).
- All data and material are given in paper and supplementary files.
- Ethics approval and consent to participate Not applicable.
- Consent for publication Not applicable.
- Competing interests The authors declare that they have no competing interests.
- Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Sharon B. Love, Email:,
- Victoria Yorke-Edwards, Email:,
- Elizabeth Ward, Email:,
- Rebecca Haydock, Email:,
- Katie Keen, Email:,
- Katie Biggs, Email:,
- Gosala Gopalakrishnan, Email:,
- Lucy Marsh, Email:,
- Lydia O’Sullivan, Email:,
- Lisa Fox, Email:,
- Estelle Payerne, Email:,
- Kerenza Hood, Email:,
- Garry Meakin, Email:,
1. ICH, International Conference on Harmonisation of technical requirements for pharmaceuticals for human use (ICH). Guideline for good clinical practice E6(R2) 2018.1996.2. Houston L, Martin A, Yu P, et al. Time-consuming and expensive data quality monitoring procedures persist in clinical trials: a national survey.
Contemp Clin Trials.2021; 103 :106290. doi: 10.1016/j.cct.2021.106290.3. Medicines for human use (clinical trials) (amendment) (EU exit) regulations 2019.2019. Accessed 5 Oct 2021.4. Beever D, Swaby L. An evaluation of risk-based monitoring in pragmatic trials in UK Clinical Trials Units. Trials.2019; 20 :556.
doi: 10.1186/s13063-019-3619-6.5. Love SB, Yorke-Edwards V, Lensen S, et al. Monitoring in practice – how are UK academic clinical trials monitored? A survey. Trials.2020; 21 :59. doi: 10.1186/s13063-019-3976-1.6. Morrison BW, Cochran CJ, White JG, et al.
- Monitoring the quality of conduct of clinical trials: a survey of current practices.
- Clin Trials.2011; 8 :342–349.
- Doi: 10.1177/1740774511402703.7.
- Baigent C, Harrell FE, Buyse M, et al.
- Ensuring trial validity by data quality assurance and diversification of monitoring methods.
- Clin Trials.2008; 5 :49–55.
doi: 10.1177/1740774507087554.8. Bakobaki JM, Rauchenberger M, Joffe N, et al. The potential for central monitoring techniques to replace on-site monitoring: findings from an international multi-centre clinical trial. Clin Trials.2012; 9 :257–264. doi: 10.1177/1740774511427325.9.
Which drugs need monitoring?
Drug and medication monitoring You might need therapeutic drug monitoring if you are prescribed medication that is easily under or over dosed. Drugs that might cause significant side effects may also be monitored. In addition, some drugs need to be monitored because the amount of drug prescribed does not correlate well with the amount that reaches the blood.
- To monitor toxic effects of some medications tests such as urea and electrolytes, creatinine and liver function tests are carried out at prescribed intervals to check kidney and liver function.
- Monitoring can help identify decreases in the efficiency and functioning of the body in processing and eliminating the drugs.
The timing of blood collection is an important part of therapeutic drug monitoring. When you take a dose of medication, the amount in the blood rises for a period of time, peaks, and then begins to fall; usually reaching its lowest level (trough) just before the next dose.
|Warfarin||Anticoagulant (anti blood clotting) therapy|
|Azathioprine||Immune system suppressant|
|Methotrexate||Immune system suppressant|
|Myocrisin||Immune system suppressant|
|Roaccutane||Used to treat or|
Drug and medication monitoring
What are the methods of drug monitoring?
Commonly Used Testing Strategy – Quantitative testing for TDM may be performed by immunoassay, high performance liquid chromatography (HPLC), or mass spectrometry. Drug results that are reported as less than the assay cutoff should be interpreted as “not detected.”
Who monitors drug safety?
Even though clinical trials provide important information on a drug’s efficacy and safety, it is impossible to have complete information about the safety of a drug at the time of approval. Despite the rigorous steps in the process of drug development, limitations exist.
Therefore, the true picture of a product’s safety actually evolves over the months and even years that make up a product’s lifetime in the marketplace. FDA reviews reports of problems with prescription and over-the-counter drugs, and can decide to add cautions to the dosage or usage information, as well as other measures for more serious issues.
On this page you will find information on:
Supplemental Applications INDs for Marketed Drugs Manufacturer Inspections Drug Advertising Generic Drugs Reporting Problems Active Surveillance
Supplemental Applications Developers must file a supplemental application if they wish to make any significant changes from the original NDA. Generally, any changes in formulation, labeling, or dosage strength must be approved by FDA before they can be made.
INDs for Marketed Drugs If sponsors want to further develop an approved drug for a new use, dosage strength, new form, or different form (such as an injectable or oral liquid, as opposed to tablet form), or if they want to conduct other clinical research or a post-market safety study, they would do so under an IND.
Manufacturer Inspections FDA officials conduct routine inspections of drug manufacturing facilities across the United States, and abroad if approved products are manufactured overseas. Manufacturers may be informed of inspections in advance, or the inspections may be unannounced.
- Inspections may be routine or caused by a particular problem or concern.
- The purpose of these inspections is to make sure that developers are following good manufacturer practice.
- FDA can shut down a facility if minimum standards are not met.
- Drug Advertising FDA regulates prescription drug advertisements and promotional labeling.
By law, a developer is prohibited from advertising unapproved uses of their product. All advertisements, such as product claims or reminder ads, cannot be false or misleading. They must contain truthful information about a drug’s effectiveness, side effects, and prescribing information.
- These advertisements can be found in medical journals, newspapers, and magazines, and on the Internet, television, or radio.
- Promotional labeling differs from drug advertisements in the way it is distributed.
- Pharmaceutical companies give out brochures or other promotional materials to physicians or consumers.
The drug’s prescribing information must accompany promotional labeling. Learn more at Prescription Drug Advertising, Generic Drugs New drugs are patent protected when they are approved for marketing. This means that only the sponsor has the right to market the drug exclusively.
Dosage form Strength Safety Quality Performance characteristics Intended use
Because generic drugs are comparable to drugs already on the market, generic drug manufacturers do not have to conduct clinical trials to demonstrate that their product is safe and effective. Instead, they conduct bio-equivalence studies and file an Abbreviated New Drug Application.
MedWatch is a gateway for reporting problems with medical products (drugs and devices) and learning about new safety information. You can subscribe to regular MedWatch safety alerts, Medical Product Safety Network (MedSun) monitors the safety and effectiveness of medical devices. FDA recruits 350 healthcare providers throughout the United States to report any medical device problems that result in serious injury or death. Each month, FDA publishes the MedSun newsletter. The newsletter gives consumers important information about medical device safety.
Active Surveillance Under the Sentinel Initiative, FDA is developing a new national system to more quickly spot possible safety issues. The system will use very large existing electronic health databases—like electronic health records systems, administrative and insurance claims databases, and registries—to keep an eye on the safety of approved medical products in real time.
Who monitors drug safety and clinical trials?
Español 药物安全通讯 Drug Safety Podcasts The FDA Drug Safety Communications posted on this web page are intended to provide important information to patients and health care professionals about new safety issues with the medicines they are taking or prescribing so they can make more informed decisions about treatment.
- Widespread or long-term use of drugs by patients may uncover side effects not discovered during the clinical trials a drug company did to get FDA approval of the medicine.
- As a result, FDA physicians and scientists continue to monitor the safety of drugs after they are approved.
- When we learn information about a potential new safety issue, we review the data from available clinical trials or other studies, case reports, and medical literature.
Based on what we find, we may require changes to the prescribing information or the patient Medication Guide. We may also release a Drug Safety Communication to alert patients and health care professionals about the issue. Read more You can get new safety information on medicines you’re prescribing or taking by signing up for email alerts about Drug Safety Communications on types of drugs or medical specialties of specific interest to you.
What are the major functions of patient monitoring?
Patient monitors measure, record, distribute and display combinations of biometric values such as heart rate, SPO2, blood pressure, temperature and more. High-capability, multi-function monitors are typically used in hospitals and clinics to ensure a high level of quality patient care.
- Portable patient monitors are designed to be compact and power efficient.
- This allows them to be used in remote areas or by paramedics to aid diagnosis in the field, enable monitoring and transmitting data to healthcare providers in other locations.
- To meet the demands faced by designers of patient monitors, we offer a broad portfolio of highly integrated microcontrollers (MCUs), graphics technology, software libraries and connectivity solutions.
This broad offering enables innovation in the design of stand-alone biometric devices such as blood pressure monitors, pulse oximeters, ECG/EKG, and other products. Our solutions support patient monitoring functions like low-noise analog signal conditioning, touch-sensing technology, LCD control, wired and wireless connectivity, motor control and high-speed memory.
What is the importance of monitoring the process?
Process monitoring can ensure that you’re executing project activities. This type of monitoring is common in situations where superiors require updates on project task implementation. It also helps with informing all project staff of the next tasks to accomplish and how they’re performing in the implementation process.
What does monitoring mean in clinical trials?
Monitoring is defined as the act of overseeing the progress of a clinical trial, and of ensuring that it is conducted, recorded, and reported in accordance with the protocol, SOPs, The Principles of GCP, and the Medicines for Human Use (Clinical Trails) Regulations – where applicable. The purpose of monitoring is to verify that:
The rights and well-being of the human subjects are protected The reported trial data are accurate, complete and verifiable from source documents The conduct of the trial is in compliance with the currently approved protocol/amendment(s), GCP and the applicable regulatory requirements.
Monitoring is an integral role in the quality control of a clinical trial and is designed to verify the ongoing quality of the study. All clinical trials sponsored or co-sponsored by one or more of the Partner Organisations will be monitored as described in this SOP. SOP: Clinical Trial Monitoring (7.1MB)
What does FDA post market drug safety monitoring mean?
Postmarketing surveillance (PMS), also known as post market surveillance, is the practice of monitoring the safety of a pharmaceutical drug or medical device after it has been released on the market and is an important part of the science of pharmacovigilance.