Joint Research Office for UCL/UCLH/Royal Free

Transcription

1 Joint Research Office for UCL/UCLH/Royal Free Standard Operating Procedure (SOP) for Setting up and Controlling External Agreements for Hosted Studies SOP ID Number Version Number Date of Authorisation Effective Date /09/ /09/2011 Review Date 12/09/2013 (or earlier as required) Author: Name and Job Title External Stakeholders Consulted: Darla Champigny, Contracts & Legal Affairs Manager UCLH pharmacy department SOP e-document kept: S: \Contracts\SOPs Revision Chronology Previous SOP ID Number Effective Date Reasons for Change Author Not applicable Page 1 of 24

2 ACRONYMS CRO CTIMP GCP ICH IMP JRO mcia mcta mnca NIHR RSS PI ReDA QA RM&G RFH SI SOP UCL UCLH Contract Research Organisation Clinical Trial of Investigational Medicinal Products Good Clinical Practice International Conference on Harmonisation Investigational Medicinal Product Joint Research Office for UCL/UCLH/Royal Free Model Clinical Investigation Agreement Model Clinical Trial Agreement Model Agreement for Non-commercial Research National Institute for Health Research (NIHR) Research Support Services (RSS) Principal Investigator Online Research Database Quality Assurance Research Management & Governance Royal Free Hampstead NHS Trust Statutory Instrument Standard Operating Procedure University College London University College London Hospitals NHS Foundation Trust DEFINITIONS Author Clinical Investigation (of a device) Clinical Trial Contract Research Organisation Guideline The member of staff responsible for co-ordinating and producing the standard operating procedure through development of the first/revised version to final draft. Any systematic investigation or study in or on one or more human subjects, undertaken to assess the safety and/or performance of a medical device. MEDDEV 2.7.1, Revision 3, December Any investigation in human subjects intended to discover or verify the clinical, pharmacological and/or other pharmacodynamic effects of one or more investigational medicinal product(s), and/or to identify any adverse reactions to one or more investigational medicinal products(s) and/or Study absorption, distribution, metabolism and excretion of one or more investigational product(s) with the object of ascertaining its (their) safety and/or efficacy. NIHR RSS Framework (Appendix 1 Glossary of Terms & Acronyms) A person or an organisation who is contracted by a Sponsor to take on any of all of the Sponsor s Clinical Trial-related duties, although the ultimate responsibility for the quality and integrity of the Clinical Trial data remains with the Sponsor. ICH Topic E6, Guideline for Good Clinical Practice, CPMP/ICH/135/95, July 2002 (R1) 09/09/WC pdf A guideline provides an additional framework to support operational decisions and courses of actions. Page 2 of 24

3 Investigational Medicinal Product Non-CTIMPs A pharmaceutical form of an active substance or placebo being tested, or to be tested, or used, or to be used, as a reference in a clinical trial, and includes a medicinal product which has a marketing authorization but is, for the purposes of the clinical trial: (a) used or assembled (formulated or packaged) in a way different from the form of the product authorised under the authorization, (b) used for an indication not included in the summary of product characteristics under the authorization for that product, or (c) used to gain further information about the form of that product as authorised under the authorization. SI2004/ All other research that does not include CTIMPs (clinical trials of investigational medicinal products). Where a Non-CTIMP Interventional Study is specified below, it refers to a non- CTIMP that involves a clinical intervention. Participating Site Principal Investigator SOP Sponsor Where a Non-CTIMP Non-interventional Study is specified below, it refers to a non-ctimp that does not involve a clinical intervention. Any organisation participating in a research study in a manner that means they are not acting as the Sponsor for that Study. Any involvement an Organisation may have in a Study form acting as a patient identification centre (PIC), sharing data or hosting a clinical trial when not acting as the Sponsor deems as host site. NIHR RSS Framework (Appendix 1 Glossary of Terms & Acronyms) The leader responsible at either RFH or UCLH for a team of individuals conducting a study. Detailed, written instructions to achieve uniformity of the performance of a specific function. As defined by RSS: Individual, organisation or group taking on responsibility for securing the arrangements to initiate, manage and finance a study. (A group of individuals and/or organisations may take on sponsorship responsibilities and distribute them by agreement among the members of the group, provided that, collectively, they make arrangements to allocate all the responsibilities in this research governance framework that are relevant to the study.) As defined by SI2004/1031: In relation to a clinical trial, the person who takes responsibility for the initiation, management and financing (or arranging the financing) of that trial. NIHR RSS Framework (Appendix 1 Glossary of Terms & Acronyms) Stakeholders SI2004/ Key staff either within the Trust/University or external to the organisation(s) who may need to be consulted as part of the SOP development process e.g. service support departments including Pharmacy and the Clinical Research Facility. Page 3 of 24

4 Joint Research Office for UCL/UCLH/Royal Free Standard Operating Procedure (SOP) for Setting up and Controlling External Agreements for Hosted Studies 1. PURPOSE This SOP will provide the procedure for setting up and controlling external agreements prior to the start of a clinical research study for hosted CTIMPs and non-ctimps. It has been written with reference to The Medicines for Human Use (Clinical Trials) Regulations 2004, The Medicines for Human Use (Clinical Trials) Amendment Regulations 2006, the guidance and tools available on the NIHR website: and in accordance with the RM&G standards required by the National Institute for Health Research (NIHR) Research Support Services (RSS) Framework. 2. JOINT RESEARCH OFFICE FOR UCL/UCLH/ROYAL FREE POLICY All SOPs produced from the JRO must be used in conjunction with local NHS Trust and UCL policies and procedures. Where applicable there is also a requirement to include stakeholder engagement as appropriately identified. The JRO represents both the Sponsor and Participating Site, depending on the type of research study. The JRO is responsible for ensuring that appropriate RM&G processes are in place. 3. BACKGROUND All SOPs must comply with the following frameworks and legal requirements: Research Governance Framework for Health and Social Care 2005 (2 nd Edition) NIHR RSS Framework Good Clinical Practice (GCP) European Directives for CTIMPs as 2001/20/EC and 2005/20/EC (these Directives were transposed into UK law as statutory instruments SI2004/1031, SI2006/1928) and subsequent amendments incorporating elements of ICH GCP tripartite guidelines (E6) Human Tissue (Quality and Safety for Human Application) 2007 Medical Devices Regulations 2002 Ionising Radiation (Medical Exposure) Regulations 2000 (IRMER) Human Tissue Act 2004 Data Protection Act 1998 Mental Capacity Act SCOPE OF THIS SOP This SOP relates to setting up and controlling external agreements for all commercially sponsored and non-commercially sponsored clinical research hosted by UCL, UCLH and RFH. External agreements are used to document and agree aspects of the relationship including (but not exclusively): Roles and responsibilities Financial and legal considerations including indemnity Termination considerations Page 4 of 24

5 Standards of service Regulatory obligations including Data Protection Intellectual property considerations Confidentiality obligations This SOP is to be used in conjunction with any internal contracting guidance documents that have been approved by the Contracts & Legal Affairs Manager. This SOP does not cover: Setting up and controlling agreements with internal parties (Service Support Departments). Please refer to the current version of the JRO/RM&G SOP for Controlling Internal Agreements (please note that all the SOPs referenced in this SOP are listed at Appendix 3). Providing and managing external agreements for UCL sponsored CTIMPs. UCL sponsored CTIMP SOPs are managed by the Quality Assurance Manager (CTIMPs) and therefore developed and published through a separate process. A list of published UCL sponsored CTIMP SOPs are available at: Providing and managing external agreements for non-ctimp research sponsored by UCL, UCLH or RFH. Please refer to the current version of the JRO/RM&G SOP for Managing and Providing External Agreements for Sponsored Non-CTIMP Studies. Issuing honorary research contracts and/or letters of access through the Research Passport Scheme in conjunction with Human Resources 5. RESPONSIBLE PERSONNEL Table 1 below outlines the key staff responsible for developing SOPs and a summary of their responsibilities. Responsibility Undertaken by Activity 1 Research Administrator Returns the final, signed hard copy(ies) of the agreement to the Sponsor, and/or other relevant external party(ies) after NHS permission has been issued and upon instruction by the Contract Manager (or Senior Research Administrator, Database & Information Officer, or Research Network Co-ordinator, as applicable) and notifies the instructing party, as appropriate, when this has been done so that such activity can be logged 2 Senior Research Administrator or Database & Information Officer Registers, after first contact and receipt of all necessary study documentation, the study on ReDA Provides key study details (including external parties) and communicates such information to the Contract Manager to initiate the external agreements process Allocates all complex studies to the applicable Research Network Co-ordinator to progress Supports the Contract Manager, as needed, with simple study-specific information Page 5 of 24

6 Responsibility Undertaken by 2 Senior Research Administrator or Database & Information Officer Activity Registers, after first contact and receipt of all necessary study documentation, the study on ReDA Provides key study details (including external parties) and communicates such information to the Contract Manager to initiate the external agreements process Allocates all complex studies to the applicable Research Network Co-ordinator to progress Supports the Contract Manager, as needed, with simple study-specific information 3 Research Network Co-ordinator Provides key study details for complex studies (includes external parties) and communicates such information to Contract Manager to initiate the external agreements process Supports the Contract Manager, as needed, with complex study-specific information Suggests the type of agreement required according to the type of study. Returns the Sponsor s (and/or other relevant external party(ies) s hard copy(ies) of the agreement after NHS permission is issued to the Contract Manager (or directly to the Research Administrator, as applicable) to return Scans and uploads a PDF copy (required for studies registered on or after 1 st March 2011) of the signed agreement onto ReDA and files a copy within the JRO R&D study file in line with the current version of the JRO/RM&G SOP for Filing 4 Contract Manager Assesses and chooses what type of external contractual arrangements need to be put in place based on the study details provided Uses (where possible) and encourages the use of standard templates without modifications and/or framework agreements to minimise legal review. Performs legal review and negotiates the terms of all external study agreements Keeps log of key details of the contracts for each study on the team spreadsheet and ReDA Liaises with the PI (or a member of his/her research team), as needed, to confirm studyspecific details Page 6 of 24

7 Responsibility Undertaken by Activity 4 Contract Manager Provides legal guidance to the Cost Accountant, as requested, on financial appendix wording. Collects the finalised financial appendix from the Cost Accountant (or, where appropriate, works with the Cost Accountant to obtain a finalised financial appendix), and incorporates it into the body of the agreement Liaises, as appropriate, with pharmacy to confirm drug-related details and/or costs Ensures that the final version of each study agreement incorporates all contractual terms agreed by all parties Obtains the applicable UCL/UCLH/RFH signature(s) from an authorised signatory on final hard copy version of agreement by way of directly bringing document(s) or submitting document(s) via a Research Administrator or signatory s personal assistant (or in any other way specified by the applicable authorised signatory). Gives the fully signed study agreement(s) to the Senior Research Administrator, Database & Information Officer, or Research Network Coordinator prior to issuing NHS permission 5 UCL Research Services Department within UCL Finance that manages university costs 6 Cost Accountant Collects all study-specific costs from the applicable NHS service support departments Liaises with UCL Research Services, where applicable, to obtain details to be included in the financial appendix Collects investigation times from the PI (or a member of his/her research team) Calculates the study budget, which may include per patient fees and one-off fees Completes the agreement financial appendix (or, where appropriate, works with the Contract Manager to complete the financial appendix, but in all situations, leads the process of approving budget-related items) Negotiates the financial appendix, including the study budget, with external parties Finalises the financial appendix, including the study budget Issues the cost centre number allocated to the study Page 7 of 24

8 Responsibility Undertaken by 7 Contracts & Legal Affairs Manager Activity Oversees Contract Managers, determines how studies will be allocated to Contract Managers, and provides guidance on contract negotiation queries, as needed, to Contract Managers 8 Head of Risk and Regulation Provides guidance on insurance, risk and conflict of interest matters 9 Authorised Signatory(ies) Member(s) of senior management authorised to sign research contracts on behalf of UCL/UCLH/RFH 10 Archivist Retains the external agreements in line with the current version of the JRO/RM&G SOP for Closedown of Studies 6. PROCEDURE 6.1 Overview Procedure Activity 1 Recording Contract Details When the Contract Manager is allocated the contract(s) for a study, he/she is to add a record to the team spreadsheet and is to keep updating the spreadsheet and ReDA as key negotiating activities occur. 2 Choosing Agreement Template The Contract Manager is to use the key study details received from the Senior Research Administrator, Database & Information Officer, or Research Network Coordinator and follow the process for choosing an agreement outlined in the flow diagram in Appendix 1. If the Contract Manager is unsure of the template to be used, he/she is to consult the Contracts & Legal Affairs Manager for guidance. 3 Reviewing and Negotiating Agreement Content The Contract Manager is to follow the process outlined in Section 6.4 (which provides instructions and basic principles) for reviewing and negotiating the content of each agreement. Should the Contract Manager have queries regarding accepting certain clauses or other type of content in the agreement, he/she is to consult the Contracts & Legal Affairs Manager for guidance. 4 Finalising Agreement Once the content has been agreed by all parties to the agreement, the Contract Manager is to request partially signed agreements from the other party(ies). Page 8 of 24

9 Procedure 5 Obtaining Signatures and Submitting prior to NHS Permission Activity The Contract Manager is to check the partially signed, hard copy agreements against the last agreed e-version and then, if they are satisfactory, obtain the trust signatory s signature. The Contract Manager is to give the fully signed study agreement(s) to the Senior Research Administrator, Database & Information Officer, or Research Network Co-ordinator (as applicable) prior to the applicable RM&G member issuing NHS permission. The provision of a fully signed agreement is a necessary governance check for granting NHS permission. 6 Distributing Fully Signed Agreements After NHS permission has been granted, the Research Administrator is to send the external party s(ies ) hard copy(ies) back to them once authorised by the Contract Manager (or the person giving NHS permission) or, as applicable, forward the external party s(ies ) copy(ies) to the PI team for them to return. The Research Administrator is to (if the Contract Manager, Senior Research Administrator, or Research Network Coordinator has not already done so) retain at least one original for the trust. 7 Filing Fully Signed Agreement The applicable RM&G member (i.e. the person giving NHS permission) is to file an original copy within the JRO R&D study file and upload a scanned PDF copy to ReDA, all in accordance with the current version of the JRO/RM&G SOP for Filing. If the Contract Manager last had the trust copy, he/she is to give to the applicable RM&G member to file/upload. 8 Retaining Fully Signed Agreement The Archivist is responsible for the retention of the trust original, signed agreement in line with the current version of the JRO/RM&G SOP for Closedown of Studies. 9 Dissemination & Training After this SOP has been authorised, there is a minimum of 3 weeks for the users to approach the Author with regards to training needs on the SOP, after which the SOP will be implemented. All users within the JRO are required to sign the RM&G SOP log as confirmation that they have read and understood the relevant SOP. The RM&G SOPs will be published on the JRO website: An will be sent to relevant users to communicate that this SOP has been authorised and implemented within a minimum of 3 weeks. The will also provide details as to where the SOP can be found electronically. New employees will be trained on this SOP within the first weeks of their employment as an induction programme. Page 9 of 24

10 6.2 Recording Contract Details When the Contract Manager is allocated the contract(s) for a study (which may be determined as a result of Contract Managers being assigned to disease-specific divisions and may come by way of a notification in ReDA), he/she is to add a record to the team spreadsheet, which is to be retrieved at: S/Contracts/Contracts Spreadsheets/Contracts spreadsheet [Current month current year] or, if moved upon approval by the Contracts & Legal Affairs Manager, where he/she so designates. The study/contract details are to be added to the applicable sheet (e.g. for a UCLH hosted study with a non-commercial sponsor, an entry is to be made to the sheet: Noncommercially spons ), and the Contract Manager is to ensure that he/she inserts all key details (including ReDA number, sponsor, study title, date received, and Contract Manager name) The study will have already been added to ReDA by the applicable RM&G member. The Contract Manager is to update ReDA and the team spreadsheet as key negotiating activities occur (with the dates upon which each occurs). Some examples of key negotiating activities include, but are not limited to, the following: contract revision sent to Sponsor, contract revision received from Sponsor, contract agreed, partially signed copies requested, partially signed copies received, contract fully signed It is imperative that the above referenced key contract details are recorded and updated accordingly, as they are used in managing the study portfolio, recording metrics, and utilising such metrics to manage/change the contracts process (including setting target time lines). 6.3 Choosing Agreement Template The Contract Manager will be responsible, utilising the key study details and the flow diagram in Appendix 1, for choosing the appropriate agreement template(s) to be used in a study. If the Contract Manager is unsure which type of agreement template should be utilised or whether an agreement is needed at all, he/she is to consult with the Contracts & Legal Affairs Manager. Note that if the contract activity involves executing an amendment to an existing agreement (rather than setting up a new agreement), the Contract Manager is to utilise the template that is made available to him/her (usually from the Sponsor), review the suggested amendment against the existing contract to determine what the changes are, confirm with the appropriate internal parties whether the suggested change(s) is/are acceptable (for example, confirm financial changes with the Cost Accountant), record important details as per the process in sub-section 6.2, and follow the steps in this SOP from sub-section 6.5 to the end. If the Contract Manager is unsure which internal party(ies) he/she should consult regarding a suggested change, he/she is to discuss with the Contracts & Legal Affairs Manager The Contract Manager is to use the key study details received from the Senior Research Administrator, Database & Information Officer, or Research Network Co-ordinator and follow the process for choosing an agreement outlined in the flow diagram in Appendix 1. If the Contract Manager is unsure of the template to be used, he/she is to consult the Contracts & Legal Affairs Manager for guidance The templates specified in the flow diagram in Appendix are to be retrieved from the following IT shared server: S:\Contracts. For all of the templates specified in this subsection 6.3.3, the Contract Manager is to access and use the template with the title as it is specified below or an updated version. For some contract templates, it is appropriate to use a range of template appendices (for example, at the time of writing this SOP, the Royal Free mcta comes with a range of financial appendices, A to D, and the Sponsor is to choose one option for use with the contract, which the Contract Manager is to then Page 10 of 24

11 confirm with the Cost Accountant). Should a Contract Manager determine (in consultation with the Contracts & Legal Affairs Manager, as appropriate) that it is more appropriate to use a different template from any of the existing templates in this sub-section for a particular study, he/she is to have a reasonable, justifiable, and documented rationale for a such a decision and is to use a template that covers all key areas, which may include but are not limited to the following: applicable laws / documents to follow (e.g. in a CTIMP, The Medicines for Human Use (Clinical Trials) Regulations 2004 and the protocol), liabilities and indemnity, confidentiality, data protection, publication, intellectual property and know-how, financial arrangements, term / termination, dispute resolution, governing law, monitoring, pharmacovigilance, and division of responsibilities mcta: : UCLH: S/Contracts/Commercial Trials/Model Agreements/Model_Clinical_Trial_Agreement(2006)(Updated).doc : RFH: S/Contracts/Commercial Trials/Model Agreements/Royal Free/Model_Clinical_Trial_Agreement(2006)(Updated)_Royal Free.doc CRO mcta: : UCLH: S/Contracts/Commercial Trials/Model Agreements/Model_CRO_Clinical_Trial_Agreement(2007)(Updated).doc : RFH: S/Contracts/Commercial Trials/Model Agreements/Royal Free/Model_CRO_Clinical_Trial_Agreement(2007)(Updated)_Royal Free.doc mcia: : UCLH: S/Contracts/Commercial Trials/Model Agreements/Model_Clinical Investigation_Agreement(2008)(devices)(updated).doc : RFH: S/Contracts/Commercial Trials/Model Agreements/Royal Free/Model_Clinical Investigation_Agreement(2008)(devices)(updated)_Royal Free.doc CRO mcia: : UCLH: S/Contracts/Commercial Trials/Model Agreements/Model_CRO_Clinical Investigation_Agreement(2008)(devices)(updated).doc : RFH: S/Contracts/Commercial Trials/Model Agreements/Royal Free/Model_CRO_Clinical Investigation_Agreement(2008)(devices)(updated)_Royal Free.doc non-ctimp Interventional Study agreement: At the time of writing this SOP, there is no non-ctimp Interventional Study agreement template in S:\Contracts, so the Contract Manager is to evaluate, on a case-by-case basis, whether an adapted version of templates we do have or have used in the past would be appropriate to use. The Contract Manager is to, as appropriate, consult with the Contracts & Legal Affairs Manager. The template must cover all key areas, which may include but are not limited to the following: applicable laws / documents to follow (e.g. in a CTIMP, The Medicines for Human Use (Clinical Trials) Regulations 2004 and the protocol), liabilities and indemnity, confidentiality, data protection, publication, intellectual property and know-how, financial arrangements, term / termination, dispute resolution, governing law, monitoring, pharmacovigilance, and division of responsibilities non-ctimp Interventional Study CRO agreement: At the time of writing this SOP, there is no non-ctimp Interventional Study CRO agreement template in S:\Contracts, so the Contract Manager is to evaluate, on a case-by-case basis, whether an adapted version of templates we do have or have used in the past Page 11 of 24

12 would be appropriate to use. The Contract Manager is to, as appropriate, consult with the Contracts & Legal Affairs Manager. The template must cover all key areas, which may include but are not limited to the following: applicable laws / documents to follow (e.g. in a CTIMP, The Medicines for Human Use (Clinical Trials) Regulations 2004 and the protocol), liabilities and indemnity, confidentiality, data protection, publication, intellectual property and know-how, financial arrangements, term / termination, dispute resolution, governing law, monitoring, pharmacovigilance, and division of responsibilities Adapted Observational mcta: : UCLH: S/Contracts/Commercial Trials/Model Agreements/Observational_(noninterventional)_studies/Model_Clinical_Trial_Agreement_Observational(2006)(Upd ated).doc : RFH: S/Contracts/Commercial Trials/Model Agreements/Royal Free/Observational_(noninterventional)_studies/Model_Clinical_Trial_Agreement_Observational(2006)(Upd ated)_royal Free.doc Adapted Observational CRO mcta: : UCLH: S/Contracts/Commercial Trials/Model Agreements/Observational_(non-interventional)_studies/ Model_CRO_Clinical_Trial_Agreement_Observational(2006)(Updated).doc : Royal Free: S/Contracts/Commercial Trials/Model Agreements/Royal Free/Observational_(non-interventional)_studies/ Model_CRO_Clinical_Trial_Agreement_Observational(2006)(Updated)_Royal Free.doc mnca: S/Contracts/Non-commercial UCLH and RFH Hosted Studies/Model Agreements 2008/mNCA_Final_2008.DOC Adapted MTA mnca: S/Contracts/Non-commercial UCLH and RFH Hosted Studies/Model Agreements 2008/mNCA_FINAL_2008_(with MTA clauses)_final_ doc MTA: : UCLH: S/Contracts/MTA Templates/UCLH_Material_Transfer_Agreement_v3(Jun09).doc : RFH: S/Contracts/MTA Templates/MTA_January 2010(DC)_updated_Royal Free template.doc Funding Agreement: At the time of writing this SOP, there is no Funding Agreement template in S:\Contracts, so the Contract Manager is to evaluate, on a case-by-case basis, whether an adapted version of templates we do have or have used in the past would be appropriate to use. The Contract Manager is to, as appropriate, consult with the Contracts & Legal Affairs Manager. The template must cover all key areas, which may include but are not limited to the following: applicable laws / documents to follow (e.g. in a CTIMP, The Medicines for Human Use (Clinical Trials) Regulations 2004 and the protocol), liabilities and indemnity, confidentiality, data protection, publication, intellectual property and know-how, financial arrangements, term / termination, dispute resolution, governing law, and division of responsibilities. Page 12 of 24

13 6.3.4 If the Contract Manager is unsure of the template to be used, he/she is to consult the Contracts & Legal Affairs Manager for guidance. 6.4 Reviewing and Negotiating Agreement Content Commercially-sponsored CTIMPs and Clinical Investigations: When the Contract Manager is assigned to a commercially sponsored CTIMP or Clinical Investigation (of a device), he/she is to obtain/confirm the completed financial appendix from the relevant Cost Accountant, incorporate this into the agreement template, and /send the template in Word (or other acceptable) format to the Sponsor or the CRO to insert the study-specific details (e.g. study title, estimated recruitment number, etc.) If the Sponsor or the CRO sends the agreement template first, the Contract Manager is to review what has been sent against the applicable UCLH or RFH template as well as the confirmed/completed financial appendix from the relevant Cost Accountant. Any deviations from the model template (except for those studyspecific details that have replaced the red text in the template) should be noted and, in the first instance, track-changed back to the original content. Any deviations from the completed financial appendix are to be brought to the attention of the Cost Accountant. If such financial modifications are agreed by the Cost Accountant, they are to be left in the agreement. If the Cost Accountant seeks legal advice on any modified / additional wording in the financial appendix, the Contract Manager is to provide such advice. If the Cost Accountant does not agree to some / all of the financial appendix modifications, the Contract Manager is to track-change the items that have been not agreed back to the original content After the Contract Manager s first review of the agreement (after it has already been with the Sponsor or CRO), the Contract Manager is/to /send the agreement document in Word (or other acceptable) format to the Sponsor or the CRO for review Each time the agreement is ed back by the Sponsor or the CRO to the Contract Manager, the Contract Manager is to check the version from the Sponsor or the CRO against the last version the Contract Manager has sent to ensure that there have been no changes. The use of tools that track changes to the document is strongly encouraged. If the Sponsor or the CRO has changed the content of the model template, the general rules are as follows: The Contract Manager is to accept no changes to Section 5 (Liabilities and Indemnity), except that a Sponsor may provide a higher than 5 million insurance minimum (including an insurance minimum in a foreign currency that converts to higher than 5 million) The Contract Manager is to accept little to no change to the rest of the model template with the following exception: if the change is minor, is reasonable, and does not lessen UCLH s or RFH s rights (and/or increase UCLH s or RFH s obligations), the Contract Manager may choose to accept it. Should the Contract Manager require guidance on any changes a Sponsor has requested (including a Sponsor s insistence to change Section 5), he/she is to consult the Contracts & Legal Affairs Manager. Page 13 of 24

14 Some examples of changes requested by the Sponsor or CRO that have been accepted in the past and are reasonable to consider accepting going forward are: The insertion of a clause specifying use of the Sponsor s ecrf database (where the PI has agreed to such use); The revision of clause 10.5 in the mcta to state sixty (60) days (as compared to the standard forty five (45) days) after agreement by the Cost Accountant; Some examples of changes requested by the Sponsor or CRO that have not been accepted in the past and should not be accepted going forward are: Non-commercially Sponsored Studies: The Sponsor s insurance coverage minimum falling below 5 million; Where a CRO is involved, the insertion of a clause stating that the CRO has no liability for any part of the study; The insertion of a clause granting the Sponsor an unlimited licence in respect of the trust s intellectual property rights When the Contract Manager is assigned to a non-commercially sponsored study, he/she is to obtain the completed financial appendix (if applicable, which the Cost Accountant or Research Network Co-ordinator will advise on) from the relevant Cost Accountant. Depending on what type of contract format was determined by following the flow diagram in Appendix 1, the Contract Manager is to then either: (1) review the Sponsor s template (obtained via the Research Network Coordinator or Sponsor directly) incorporating the financial appendix and /send the template in Word (or other acceptable) format to the Sponsor or (2) incorporate the financial appendix into our agreement template and /send the template in Word (or other acceptable) format to the Sponsor to insert the study-specific details (e.g. study title, estimated recruitment number, etc.). As with the commercially sponsored studies, if the Cost Accountant has sought any legal advice on any modified / additional wording in the financial appendix, the Contract Manager is to provide such advice As with the commercially sponsored studies, each time the agreement is ed back by the Sponsor to the Contract Manager, the Contract Manager is to check the version from the Sponsor against the last version the Contract Manager has sent to ensure that there have been no changes. The use of tools that track changes to the document is strongly encouraged The next sections give advice on how to review and negotiate the various types of non-commercially sponsored study agreement templates: Sponsor s template, mnca, or adapted MTA mnca: Contract Manager is to review the template / version received against the mnca (or adapted MTA mnca, as Page 14 of 24

15 appropriate) and check that the same applicable areas that are covered in the mnca (or adapted MTA mnca, as appropriate) are covered in the current version of the agreement being reviewed. Key areas are: applicable laws / documents to follow (e.g. in a CTIMP, The Medicines for Human Use (Clinical Trials) Regulations 2004 and the protocol), liabilities and indemnity, confidentiality, data protection, publication, intellectual property and know-how, financial arrangements, term / termination, dispute resolution, governing law, monitoring, pharmacovigilance, and division of responsibilities If any of the above key areas are missing or are materially different from what is in the mnca (or adapted MTA mnca, as appropriate), the Contract Manager is to add / revise wording / clauses to reflect what is contained in the mnca (or adapted MTA mnca, as appropriate). The general rule is that we want to largely achieve what is contained in the mnca (or adapted MTA mnca, as appropriate), but the Contract Manager may choose to accept any change that is minor, is reasonable, and does not lessen UCLH s or RFH s rights (and/or increase UCLH s or RFH s obligations). Should the Contract Manager require guidance on any changes a Sponsor has requested, he/she is to consult the Contracts & Legal Affairs Manager Some key principles we have followed in the past and should continue to follow are: MTA Liabilities/Indemnity: Each party is responsible for and indemnifies the other for claims arising out of their own negligence. In the past, we have rejected a Sponsor s insistence that they will not provide an indemnity for at least their negligence Intellectual Property (IP): Usually, the Sponsor owns the IP, but it is important that we have a right to use know-how for our own academic / teaching purposes. In the past, we have rejected a Sponsor s insistence that the trust had no right to use knowhow arising from the study If there is a clause that puts unique responsibilities on the PI / Pharmacy, we must confirm with them internally Contract Manager is to review the version received back from the Sponsor against the MTA template and check that nothing has been materially changed. The use of tools that track changes to the document is strongly encouraged. The general rule is that we want to largely achieve what is contained in the MTA template, but the Contract Manager may choose to accept any change that is minor, is reasonable, and does not lessen UCLH s or RFH s rights Page 15 of 24

16 (and/or increase UCLH s or RFH s obligations). Should the Contract Manager require guidance on any changes a Sponsor has requested, he/she is to consult the Contracts & Legal Affairs Manager Some key principles we have followed in the past and should continue to follow are: Liabilities: Recipient is responsible for any liability arising from use and keeping of tissues or data. Each party is responsible for and indemnifies the other for claims arising out of their own negligence. In the past, we have rejected a Sponsor s insistence that they will not provide an indemnity for at least their negligence Tissue retention: We have rejected a Sponsor s insistence to keep trust patient s tissues indefinitely where this was not reflected in the patient/participant information sheet Funding Agreement 6.5 Finalising Agreement Contract Manager is to review version received back from the Sponsor against the Funding Agreement template and check that nothing has been materially changed. The use of tools that track changes to the document is strongly encouraged. The general rule is that we want to largely achieve what is contained in the Funding Agreement template, but the Contract Manager may choose to accept any change that is minor, is reasonable, and does not lessen UCLH s or RFH s rights (and/or increase UCLH s or RFH s obligations). Should the Contract Manager require guidance on any changes a Sponsor has requested, he/she is to consult the Contracts & Legal Affairs Manager A key principle to follow is that even if the study or agreement is terminated prematurely, the Sponsor is still responsible for all costs incurred by the trust up until termination Once the content has been agreed in writing (which includes ) by all parties to the agreement, the Contract Manager is to request partially signed (wet ink) agreements from the other party(ies) equivalent to the number of parties (or, if the PI requests his/her own original, one additional copy) The Contract Manager should always have the other party(ies) sign first because UCLH and RFH require a fully-signed agreement in order to issue NHS permission. Should the other party(ies) insist on UCLH or RFH signing first, the Contract Manager is to use his/her reasonable judgment and/or consult with the Contracts & Legal Affairs Manager, where appropriate. 6.6 Obtaining Signatures and Submitting prior to NHS Permission Page 16 of 24

17 6.6.1 When the partially signed (wet ink) agreements arrive, the Contract Manager is to check the hard copies against the last agreed e-version to ensure that none of the wording and/or figures have changed. If such wording and/or figures have changed, the Contract Manager is to notify the other party that they must either send fresh, partially signed (wet ink) originals reflecting the actual agreed version or agree with the other party that we can print out a hard copy of the affected page(s) from the last agreed e-version and insert it/them into the partially signed (wet ink) originals The Contract Manager should always receive wet ink originals. Should there be an extenuating circumstance in which the other party(ies) and/or PI request, in the interest of time, that a PDF signed version suffice just for the purposes of NHS permission (with wet ink hard copies to follow in the post), the Contract Manager is to use his/her reasonable judgment and/or consult with the Contracts & Legal Affairs Manager, where appropriate Once it has been confirmed that the hard copies reflect the last agreed version (which may be an e-version) exactly, the Contract Manager is to obtain the signature of the trust signatory (refer to Appendix 2 for named signatories). This can be done in various ways, two of which include bringing the hard copies directly to a trust signatory or submitting the hard copies via a Research Administrator, Senior Research Administrator, or signatory s personal assistant (or in any other way specified by the applicable authorised signatory). If the signatory so requires, the Contract Manager is to initial the hard copies prior to submission for signature as evidence that he/she has checked the hard copies against the last agreed version (please note that a list of trust signatories at the time of writing this SOP is at Appendix 2) The Contract Manager is to give the fully signed study agreement(s) to the Senior Research Administrator, Database & Information Officer, or Research Network Coordinator (as applicable) to use in issuing NHS permission. 6.7 Distributing Fully Signed Agreements Once NHS permission has been granted, the Research Administrator, upon instruction by the Contract Manager (or Senior Research Administrator, Database & Information Officer, or Research Network Co-ordinator, as applicable), is to send the external party s(ies ) hard copy(ies) back to them and retain one original for the trust or, as applicable, forward the external party s(ies ) copy(ies) to the PI team for them to return. The Research Administrator is to (if the Contract Manager, Senior Research Administrator, or Research Network Co-ordinator has not already done so) retain at least one original for the trust. 6.8 Filing Fully Signed Agreement The applicable RM&G member (i.e. the person giving NHS permission) is to file an original copy within the JRO R&D study file and upload a scanned PDF copy to ReDA. If the Contract Manager last had the trust copy, he/she is to give to the applicable RM&G manager to file/upload, all in accordance with the current version of the SOP for Filing. 6.9 Retaining Fully Signed Agreement The Archivist is to retain the trust original, signed agreement in line with the current version of the SOP for Closedown of Studies Dissemination & Training Page 17 of 24

18 This SOP will be implemented within a minimum of 3 weeks after it has been signed-off. This provides a window of opportunity for users to contact the Author for training purposes. All users within the JRO are required to sign the RM&G SOP log as confirmation that they have read and understood the relevant SOP The RM&G SOPs will be published on the JRO website: An will be sent to relevant users to communicate that the SOP has been authorised and implemented within the 3 week timeframe. The will also provide details as to where the SOP can be found electronically. See section 10 of the SOP for more details New employees will be trained on this SOP within the first weeks of their employment as an induction programme. 7. REFERENCES JRO Website Research Governance Framework 2005 (2 nd Edition) t/dh_ pdf NIHR RSS Framework (including Appendix 1 Glossary of Terms and Acronyms) UKCRC Website for Model Agreement Templates MEDDEV 2.7.1, Revision 3, December ICH Topic E6, Guideline for Good Clinical Practice, CPMP/ICH/135/95, July 2002 (R1) pdf UK Legislation Website 8. APPENDICES Appendix 1: Flowchart for Choosing Agreement Template Appendix 2: Authorised Signatory List for each Trust Page 18 of 24

19 Page 19 of 24

20 Appendix 2 Authorised Signatories for each Trust UCLH Mr. Joe Mwanza Head of Finance and Contracts, Joint Research Office for UCL/UCLH/Royal Free Dr. Nick McNally Director of Research Support, UCL/UCLH/Royal Free Research Support Centre RFH Professor Steve Powis Medical Director, Royal Free Page 20 of 24

21 Appendix 3 List of Applicable SOPs JRO/RM&G SOP for Controlling Internal Agreements JRO/RM&G SOP for Managing and Providing External Agreements for Sponsored Non-CTIMP Studies JRO/RM&G SOP for Filing JRO/RM&G SOP for Closedown of Studies Page 21 of 24

22 9. TEMPLATES/LOGS ASSOCIATED TO THIS SOP: 1 RM&G SOP TEMPLATE 2 SOP training log (Section 12 of each SOP) 3 Individual Staff SOP and courses log 4 UKCRC Website for Model Agreement Templates (where mcta, mcta, and mnca can be found) 10. SOP DISSEMINATION & TRAINING SOPs relevant to the JRO only, will be distributed to the concerned JRO staff, by the named Author on the front page of the SOP. Staff concerned by the SOP will sign the SOP training log (12. SOP TRAINING LOG) which is part of each SOP. In addition, each JRO staff has an Individual Staff SOP and courses log and will need to update it once trained on the SOP. In some instances, the SOP or the changes to the SOP will be basic. The training will constitute of the person reading the SOP and being provided with the opportunity to ask specific questions to the author of the SOP. In some instances, the staff member being trained will carry out the procedure under supervision of the author of the SOP or under supervision of a staff member who has been trained and is using the SOP. Both trainee and trainer (should the SOP require training) will need to sign and date the SOP training log in section 12 of each SOP and the Individual staff SOP and courses log. The SOPs and relevant templates and logs will be available on the JRO website shortly after having been released. If relevant, other Departments should be ed the new SOPs or the website link to the SOP. 11. SIGNATURE PAGE Author: Name / Job Title Darla Champigny, Contracts & Legal Affairs Manager Signature / Date: Authorised by: Name / Job Title Susan Kerrison, Head of Risk & Regulation Signature / Date: Page 22 of 24

23 12. SOP TRAINING LOG 1 Name of Staff (Capital letters) Job Title: Department: Training Date I confirm that I understand & agree to work to this SOP SIGNATURE Name of Trainer (if training required) Signature Date Page 23 of 24

24 8 Name of Staff (Capital letters) Job Title: Department: Training Date I confirm that I understand & agree to work to this SOP SIGNATURE Name of Trainer (if training required) Signature Date Page 24 of 24