Conducting Phase III and Phase IV Clinical Trials

Abstract Background Despite the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) encouraging the use of risk-based monitoring for trials in 2013, there remains a lack of evidence-based guidelines on how to monitor. We surveyed the academic United Kingdom Clinical Research Collaboration (UKCRC) registered clinical trials units (CTUs) to find out their policy on monitoring of phase III randomised clinical trials of an investigational medicinal product (CTIMPs). Methods An online survey of monitoring policy with sections on the CTU, central monitoring and on-site monitoring was sent to all 50 UKCRC registered CTUs in November 2018. Descriptive data analysis and tabulations are reported using the total number answering each question. Results A total of 43/50 (86%) of CTUs responded with 38 conducting phase III randomised CTIMP trials. Of these 38 CTUs, 34 finished the survey. Most CTUs (36/37, 97%) use a central monitoring process to guide, target or supplement site visits. More than half (19/36, 53%) of CTUs do not use an automated monitoring report when centrally monitoring trials and all units use trial team knowledge to make a final decision on whether an on-site visit is required. A total of 31/34 (91%) CTUs used triggers to decide whether or not to conduct an on-site monitoring visit. On-site, a mixture of source data verification and checking of processes was carried out. The CTUs overwhelmingly (27/34, 79%) selected optimising central monitoring as their most pressing concern. Conclusion The survey showed a wide variation in phase III randomised CTIMP trial monitoring practices by academic clinical trials units within a single research-active country. We urgently need to develop evidence-based regulator-agreed guidance for CTUs on best practice for both central and on-site monitoring and to develop tools for all CTUs to use.

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Monitoring in practice – How are UK academic clinical trials monitored? A survey

10.21203/rs.2.13845/v1 ◽

2019 ◽

Author(s):

Sharon Love ◽

Victoria Yorke-Edwards ◽

Sarah Lensen ◽

Matthew R Sydes

Keyword(s):

Clinical Trials ◽

Best Practice ◽

Online Survey ◽

Research Collaboration ◽

Phase Iii ◽

Final Decision ◽

Evidence Based ◽

Conducting Phase ◽

Central Monitoring ◽

Site Monitoring

Abstract Background Despite the FDA and EMA encouraging the use of risk-based monitoring for trials in 2013, there remains a lack of evidence-based guidelines on how to monitor. We surveyed the academic United Kingdom Clinical Research Collaboration (UKCRC) registered clinical trials units (CTUs) to find out their policy on monitoring of phase III randomised CTIMP trials. Methods An online survey of monitoring policy with sections on the CTU, central monitoring and on-site monitoring was sent to all 50 UKCRC registered CTUs in November 2018. Descriptive data analysis and tabulations are reported using the total number answering each question. Results 43/50 (86%) of CTUs responded with 38 conducting phase III randomised CTIMP trials. Of these 38 CTUs, 34 finished the survey. Most CTUs (36/37, 97%) use a central monitoring process to guide, target or supplement site visits. More than half (19/36, 53%) of CTUs do not use an automated monitoring report when centrally monitoring trials and all units use trial team knowledge to make a final decision on whether an on-site visit is required. 31/34 (91%) CTUs used triggers to decide whether or not to conduct an on-site monitoring visit. On-site, a mixture of Source Data Verification and checking of processes was carried out. The CTUs overwhelmingly (27/34, 79%) selected optimising central monitoring as their most pressing concern. Conclusion The survey showed a wide variation in Phase III randomised CTIMP trial monitoring practices by academic clinical trials units within a single research-active country. We urgently need to develop evidence-based regulator agreed guidance for CTUs on best practice for both central and on-site monitoring and to develop tools for all CTUs to use.

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Monitoring in practice – How are UK academic clinical trials monitored? A survey

10.21203/rs.2.13845/v2 ◽

2019 ◽

Author(s):

Sharon Love ◽

Victoria Yorke-Edwards ◽

Sarah Lensen ◽

Matthew R Sydes

Keyword(s):

Clinical Trials ◽

Online Survey ◽

Research Collaboration ◽

Phase Iii ◽

European Medicines Agency ◽

Final Decision ◽

Evidence Based ◽

Conducting Phase ◽

Central Monitoring ◽

Site Monitoring

Abstract Despite the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) encouraging the use of risk-based monitoring for trials in 2013, there remains a lack of evidence-based guidelines on how to monitor. We surveyed the academic United Kingdom Clinical Research Collaboration (UKCRC) registered clinical trials units (CTUs) to find out their policy on monitoring of phase III randomised clinical trials of an investigational medicinal product (CTIMPs). Methods An online survey of monitoring policy with sections on the CTU, central monitoring and on-site monitoring was sent to all 50 UKCRC registered CTUs in November 2018. Descriptive data analysis and tabulations are reported using the total number answering each question. Results 43/50 (86%) of CTUs responded with 38 conducting phase III randomised CTIMP trials. Of these 38 CTUs, 34 finished the survey. Most CTUs (36/37, 97%) use a central monitoring process to guide, target or supplement site visits. More than half (19/36, 53%) of CTUs do not use an automated monitoring report when centrally monitoring trials and all units use trial team knowledge to make a final decision on whether an on-site visit is required. 31/34 (91%) CTUs used triggers to decide whether or not to conduct an on-site monitoring visit. On-site, a mixture of source data verification and checking of processes was carried out. The CTUs overwhelmingly (27/34, 79%) selected optimising central monitoring as their most pressing concern. Conclusion The survey showed a wide variation in Phase III randomised CTIMP trial monitoring practices by academic clinical trials units within a single research-active country. We urgently need to develop evidence-based regulator agreed guidance for CTUs on best practice for both central and on-site monitoring and to develop tools for all CTUs to use.

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Are We Ready for Cell Therapy to Treat Stroke?

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.621645 ◽

2021 ◽

Vol 9 ◽

Author(s):

Fernando José Rascón-Ramírez ◽

Noelia Esteban-García ◽

Juan Antonio Barcia ◽

Albert Trondin ◽

Cristina Nombela ◽

...

Keyword(s):

Clinical Trials ◽

Cell Therapy ◽

Statistical Design ◽

Basic Research ◽

Phase Iii ◽

Main Element ◽

General Description ◽

Conducting Phase ◽

Cell Therapies ◽

Routes Of Administration

Clinical trials of cell therapies that target stroke started at the beginning of this century and they have experienced a significant boost in recent years as a result of promising data from basic research studies. The increase in the information available has paved the way to carry out more innovative and varied human studies. Efforts have focused on the search for a safe and effective treatment to stimulate neuro-regeneration in the brain and to reduce the sequelae of stroke in patients. Therefore, this review aims to evaluate the clinical trials using cell therapy to treat stroke published to date and assess their limitations. From 2000 to date, most of the published clinical trials have focused on phases I or II, and the vast majority of them demonstrate that stem cells are essentially safe to use when administered by different routes, with transient and mild adverse events that do not generally have severe consequences for health. In general, there is considerable variation in the trials in terms of statistical design, sample size, the cells used, the routes of administration, and the functional assessments (both at baseline and follow-up), making it difficult to compare the studies. From this general description, possibly the experimental protocol is the main element to improve in future studies. Establishing an adequate experimental and statistical design will be essential to obtain favorable and reliable results when conducting phase III clinical trials. Thus, it is necessary to standardize the criteria used in these clinical trials in order to aid comparison. Shortly, cell therapy will be a key approach in the treatment of stroke if adequate and comprehensive levels of recovery are to be achieved.

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18 Definitive Phase III and Phase IV Clinical Trials

Handbook of Statistics - Epidemiology and Medical Statistics ◽

10.1016/s0169-7161(07)27018-x ◽

2007 ◽

pp. 546-568

Author(s):

Barry R. Davis ◽

Sarah Baraniuk

Keyword(s):

Clinical Trials ◽

Phase Iii ◽

Phase Iv

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Current Approaches to Planning and Conducting Clinical Trials of Medicinal Products for the Treatment of Crohn's Disease

The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products ◽

10.30895/1991-2919-2020-10-2-111-120 ◽

2020 ◽

Vol 10 (2) ◽

pp. 111-120

Author(s):

А. N. Bogdanov ◽

E. V. Gorbunova ◽

D. V. Goryachev ◽

E. V. Petraneva

Keyword(s):

Clinical Trials ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Clinical Research ◽

Therapeutic Effect ◽

Marketing Authorisation ◽

Methodological Approach ◽

Phase Iii ◽

Medicinal Products ◽

Conducting Phase

Accumulation of knowledge on Crohn’s disease, and development of biological products intended for the treatment of its underlying cause formed the basis for the development of objective methods for assessing the intensity of the pathological process, which in turn affected scientific approaches to the planning of clinical trials in this field. To date, many international recommendations related to planning, conduct of clinical trials, and analysis of their results, have been updated. Considerable experience has been gained with clinical trials of medicines intended for the treatment of Crohn’s disease. Therefore, the methodological approach to the planning of pivotal clinical studies needs to be reviewed. The aim of the study was to develop requirements for planning and expert evaluation of clinical trials conducted with the aim of obtaining marketing authorisation for medicinal products for the treatment of Crohn’s disease. The paper analyses regulations, recommendations, and scientific literature on the treatment of Crohn’s disease and describes the methodology for planning clinical trials. It describes the evolution of approaches to clinical research planning since biological medicines appeared. The authors substantiate the need for an integrated concept of clinical research, which covers goals, estimated therapeutic effect, design, and choice of the statistical analysis method. They also provide scientific arguments in favour of a combined primary endpoint including endoscopic remission and the assessment of treatment results by the patient. The paper lists patient eligibility criteria in terms of “inducing and/or maintaining remission of the disease”. The authors analyse the main intercurrent events, their influence on the therapeutic effect, and propose approaches to the planning of endpoints, including assessment of intercurrent events. The paper highlights the fact that the principles of planning and conducting Phase III clinical trials need to be consistent with the evidence-based strategies of reducing the risk of incorrect assessment of efficacy and safety of new medicines, and that the obtained results have to meet the requirements of the regulatory authorities at the stage of marketing authorisation.

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