.

(Agathe Guillot - GCP Inspector, 14 July 2014)

MHRA view of responsible Sponsorship

Content• Sponsor• Basis for Oversight• Investigator Oversight:

o Contracting/delegatingo Plans for oversighto Evidence of oversighto Retention of evidence

• Common findings• MHRA Expectations

Sponsor• An individual, a company, institution or organisation that takes

responsibility for the initiation, management, and/or financing of a clinical trial (Reg 3(1) of SI 2004/1031)

• Established in the EEA (or legal representative in EEA)

• Types of sponsor seen in the UK:o Commercial pharmaceutical companies,o Research councils,o Medical charities,o and Other non-commercial bodies (Trusts & Universities)

Oversight

• Watchful and responsible care• Supervision • Watchful management• Management of the performance or operation of a

person/group

Basis for oversightSponsor Responsibilities:

Global: Guidance ICH GCP E6 5.2.1, 5.2.2 and 5.2.4

EU: Directive 2005/28/EC article 7, EU Regulation 536/2014 Chapt 8

UK: Reg.3(12) of SI2006/1928

Quality Systems:

Global : Guidance ICH GCP E6 2.13, 5.1.1 and 5.2.1

EU: Directive 2005/28/EC article 2(4)

UK: Reg.28(2) of SI2006/1928, Schedule 1 part 2 (4) & (9)

Basis for oversight

Trial Master File:

Global : Guidance ICH GCP E6 2.10, 5.5.3, 5.5.4, 5.5.6,

5.5.11 and 8.1

EU: Directive 2005/28/EC articles 5 and 16 to 20

UK: Reg.31A of SI2006/1928, Schedule 1 part 2 (9)

Sponsor Oversight Summary

Trials

• Complexity of trials:o New technology, more specialised/niche vendorso More vendors within the trial to provide necessary expertiseo Involvement of CTUso Outsourced work (specialised labs, image analysis, CRF)

Co-sponsorship

• Reg.3(2) of SI2004/1031 – joint responsibility• No reference to contract information in the TMFs, as contracts are not

at a trial level • No evidence in the TMF of what aspects of the delegated “function” was

undertaken by each party • Although all staff were on the delegation log, it was not apparent from

any trial documents who were sponsor or co-sponsor staff especially if they have an honorary contract

• Training logs were incomplete, as these were split between the sponsor and co-sponsor, so not everything was available.

Delegation

Delegation

• Sponsor can delegate a task or role, but not the responsibility under the legislation

(Reg.3(12) of SI2006/1928)

• The sponsor/vendor relationship (delegation of whole departmental functions)o CTUs (Data management/statistics/project management)

Delegation Expectations

• Delegation of tasks must be in writing• Sufficiently detailed: who does what• Routinely reviewed throughout the trial lifecycle• Regular well-defined communication (documented

Reg.31A(4) of SI2006/1928)• Escalation process• Assessment program

Delegated Parties

• Examples include:o Investigatorso Clinical Trials Units (CTU)o Third parties e.g. laboratories

Common Issues

Sponsor and delegated parties (DP):• Sponsor or DP not undertaking their responsibilities• DP undertaking activities not formally delegated• Inadequate detail of the activities delegated • Partnership agreement for function not considered formal

delegation, so no clarity in trial documents that activities performed by vendor

• Responsibility of reporting of SUSARs to CA not clear

Oversight

Mechanisms for oversight• Monitoring (on site or remote) and audits• Review of monitoring reports & co-monitoring visits• Minuted meetings with study team • Review of progress reports (e.g.ASR/APR/Organisation Report)• Spot checks (processes and trial documents)• Documentation to support key decision making• Plan for review of vendors performance • Defined process for escalation and resolution of issues

Expectations

• Formal procedures for addressing oversight• Proactive & ‘up front’ determination of the levels of oversight

needed for a trial/project • Justified rationale for levels of oversight• Flexible oversight plans to permit changes

Risk assessment and oversight mitigation plan

Expectations

Then:• Documentation of what has been performed• Contemporaneous evidence of compliance • Retained in the TMF

Issues• Documentation to reconstruct appropriate oversight• No evidence of TMF issues addressed/closed when raised

by sponsor• No evidence of sponsor review of status reports• Informal meetings so not documented: attendance and

decisions unclear

Retention of documentation

• Oversight documentation: contemporaneously retained

• TMF = o individual to the organisation (index)o story of the trialo all documentation produced during the trial (what

happened and compliance with SOPs)

MHRA Expectations

• Follow current Regulations• Procedures in place and being followed• Follow protocol, follow randomisation procedure• Mechanism for non-compliances – appropriate

management of issues• Staff appropriately trained • Oversight of contracting or outsourcing

Contracting

Contracting

TMF/Documentation

Expectations

• Formal process: vendors identification and assessment • Mechanisms for assessment depending on GCP criticality• Assessment and decision documented• Retention – where/how is this referenced if not in the TMF

Common IssuesSponsors• No/inadequate assessment• Commitment prior to any

issues being resolved• Not considered trial data, so

not in TMF or referenced• No awareness of third party

outsourcing

Vendors• Unable to deliver to a

required standard

(e.g. laboratory being unable to comply with GCP)

Issues for sponsors to be aware of• Pressure on study team:

o timeo funding

• Academic qualifications:o CI, rotating registrars conducting different parts of the trial,

pressure to write up publication

Sponsorship responsibility

• Awareness of what is to be done• Clear who/what responsibility• Appropriate mechanisms to ensure oversight • Use of tools to manage risk:

o sponsor audits, visibility to trial team, presence of sponsor on project team/copied into minutes

• Management of data, close out and publication:o no review on outputs from trial, no process for publication

review despite claims of compliance

Summary

• Basis for sponsor oversight • Delegations and our expectations• Oversight and the various mechanisms that can be used• Contracting and our expectations • Sponsor responsibilities

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Questions ?

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