1. Sponsor The sponsor is the individual, company, institution or organisation, which takes on _______ responsibility for the initiation, management (or arranging the initiation and management) of and/or financing (or arranging the financing) for that research. The sponsor takes primary responsibility for ensuring that the design of the study meets appropriate _______ and that arrangements are in place to ensure appropriate ______ and ___________ (HRA)

2. Research Governance Framework Confirming that everything is ready for the research to begin : -taking on responsibility for putting and keeping in place arrangements to initiate, manage and fund a study; -satisfying itself the research protocol, research team and research environment have passed appropriate scientific quality assurance; -satisfying itself the study has ethical approval before it begins; -for clinical trials involving medicines, seeking a clinical trial authorisation and making arrangements for investigational medicinal products

3. Research Governance Framework Satisfying itself that arrangements are kept in place for good practice in conducting the study, and for monitoring and reporting, including prompt reporting of su spected unexpected serious adverse events or reactions.

4. Research Governance Framework Sponsorship initiate, manage and fund a study; scientific quality assurance; ethical approval clinical trial authorisation and investigational medicinal products AND Good practice in conducting the study

5. Clinical trial for gene therapy, US, 1999 18-year-old Jesse Gelsinger is understood to be the first person publicly identified as having died in a clinical trial for gene therapy.

6. Clinical trial for gene therapy, US, 1999 “Good practice in conducting the study”

7. The anti-psychotic drug trial, US, 2004 Six months after starting the trial, he stabbed himself to death, reportedly leaving behind a suicide note

8. The anti-psychotic drug trial, US, 2004 “Good practice in conducting the study”

9. Northwick park 2006 In what became known as the Elephant Man trial, six healthy young men were treated for organ failure after experiencing a serious reaction within hours of taking the drug TGN1412 in a clinical trialsix healthy young men were treated for organ failure

10. Northwick park 2006 The report said Parexel, the company managing the trial, had been unclear about a safe dose to start testing on humans and it should have tested the drug on one person at a time.Parexel “Victim set to win £2m payout”

11. Northwick park 2006 “satisfying itself the research protocol, research team and research environment have passed appropriate scientific quality assurance”

12. France drug trial: brain-dead man dies in hospital 2016 One person has been left brain-dead and five others hospitalised after a clinical trial of a drug went wrong, the French health ministry announced todayFrench health ministry

13. France drug trial: brain-dead man dies in hospital 2016 “Good practice in conducting the study”

14. 85% of expenditure on medical research wasted “Most scientific studies are wrong, and they are wrong because scientists are interested in funding and careers rather than truth.” Researchers are publishing studies that are too small, conducted over too short a time, and too full of bias in order to get promoted and secure future funding

15. Waste Chalmers, Glasziou, and others identify five steps that lead to 85% of biomedical research being wasted. Richard Smith: Medical research—still a scandal 31 Jan, 14 | by BMJ

16. 5 reasons for waste? ?

17. Waste Firstly, much research fails to address questions that matter. For example, new drugs are tested against placebo rather than against usual treatments. Or the question may already have been answered, but the researchers haven’t undertaken a systematic review that would have told them the research was not needed. Or the research may use outcomes, perhaps surrogate measures, that are not useful.

18. Waste Secondly, the methods of the studies may be inadequate. Many studies are too small, and more than half fail to deal adequately with bias. Studies are not replicated, and when people have tried to replicate studies they find that most do not have reproducible results.

19. Waste Thirdly, research is not efficiently regulated and managed. Quality assurance systems fail to pick up the flaws in the research proposals. Or the bureaucracy involved in having research funded and approved may encourage researchers to conduct studies that are too small or too short term.

20. Waste Fourthly, the research that is completed is not made fully accessible. Half of studies are never published at all, and there is a bias in what is published, meaning that treatments may seem to be more effective and safer than they actually are. Then not all outcome measures are reported, again with a bias towards those are positive.

21. Waste Fifthly, published reports of research are often biased and unusable. In trials about a third of interventions are inadequately described meaning they cannot be implemented. Half of study outcomes are not reported

22. The legal responsibilities of the sponsor of CTIMP A. Authorisation for clinical trials and research ethics committee opinion B. GCP and the conduct of clinical trials C. Pharmacovigilance D. Manufacture and labelling of investigational medicinal product [MHRA Guide ISBN 978 0 11 708107 9]

23. MHRA GCP Inspection Critical Findings Major Findings Other Findings

24. MHRA GCP Inspection 2004 CI s: Patrick Hourigan and David Strain 5 Major Findings 1.Sponsor Oversight 2.Quality Systems 3.Medical Oversight 4.Monitoring 5.Training

25. Thank you Any questions