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ОглавлениеBefore Initiation
This chapter describes the handling of contracts specifically for investigator-initiated clinical studies.
Regulatory Reference
! ICH GCP Guideline, 1.17, 4.1-4.6, 5.1.2, 5.1.4, 5.9
Responsibilities
The sponsor-investigator has to ensure that the contract between him and the relevant company, e.g. the Contract Research Organisation (CRO) or the pharmaceutical company, contains the following items, as far as appropriate, for the relevant type of contract.
• Sponsor’s name and address
• CRO’s name and address (if applicable)
• Protocol title and number
• Indemnification language
• Confidentiality agreement (if not in a separate document)
• Estimated start and finish dates of the trial
• Estimated number of subjects expected to enrol from the study site (can also specify for each study site in a multicentre trial)
• Budget information and payment schedule, including terms for delays and termination of the study
• The definition of a ‘completed’ subject (i.e. fully-paid)
• Description of the reimbursement policies and process for study subjects who experience an adverse event (AE) or who are injured while participating in the study
• A list of the responsibilities assigned to the study site
• A statement of whose Standard Operating Procedures (SOPs) will be followed (i.e. from the sponsor, the CRO, or the study site)
• Publication rights
• Data ownership rights
In addition, the Research Director and the Legal Department should review the integrity of the abovementioned aspects.
Advice - Hints and Tips
Please note that all agreements have to be approved by the Legal Department, a representative of the company and by you.
If the company is preparing the agreement, two originals will be prepared and sent to you for signature. A copy will be retained in the interim; this copy will be discarded when the signed original is returned. You have to sign both originals, keep one of them, and return the other to the company.
Any contractual agreement must be in place before any subjects are enrolled in the study.
Forms and Templates
The scheme listed below shows the characteristic parts of a model agreement with the pharmaceutical company supplying the study’s investigational (new) drug or IMP.
Purpose and Objective of Agreement
At first, your role is defined, e.g. as sponsor-investigator to conduct a research project involving the pharmaceutical company’s compound drug(s). This role is designated in accordance with the terms defined in the protocol of the study and the specific ICH GCP definitions.
The study will be performed under the supervision and responsibility of you, the sponsor-investigator.
Protocol
The study is carried out exactly in accordance with the terms of the corresponding protocol. In case the manufacturer only provides the IMP, the company may wish to review the protocol prior to its implementation. Any amendments or modifications must be in writing and agreed upon by both parties (as appropriate).
see 4
Study Protocol
Investigator’s Brochure (IB)
You must be familiar with this document before the study commences. The pharmaceutical company should answer any product-related questions that may emerge from the study site(s).
see 11
Investigator’s Brochure/Summary of Product Characteristics
Sponsor-Investigator’s Obligations
You should carry out the study in accordance with any and all applicable rules and regulations (such as the Declaration of Helsinki and the Good Practices ICH GCP, Good Laboratory Practice [GLP] and/or GMP) as well as in strict observance of the study protocol. Furthermore, another obligation is to agree to submit drafts of all substantial amendments (e.g. substantial protocol amendments) to the health authorities and to the Ethics Committee in a timely manner.
Other tasks include being in charge of implementing the study and being responsible for any study-related activities such as monitoring, data management (e.g. data entry, validation), auditing, intermediary and/or final data analysis, and preparation of the final study report and the final publication.
see 17
Data Management
see 21
Source Data Verification
see 23
Monitoring
see 26
Final Study Report and Publication
Confidentiality
Prior to or during the course of the study, the company may provide you with confidential information, including but not limited to the IB. The information may not be disclosed to anyone else without prior approval of the company in writing.
An additional task might be to take any reasonable steps so that your collaborators will be under the same confidential obligation.
Ethics Committee Approval
Written approval for the protocol and all amendment(s) - similar to the content of the patient information form - must be obtained by you from a properly constituted Ethics Committee (e.g. at the study site), according to the local law prior to the commencement of the study.
see 14
Ethics
Clinical Trial Application
A clinical trial application (CTA) in accordance to local regulations must be submitted to the national health authority by the sponsor-investigator. You are responsible for ensuring that all requirements are met in accordance to local regulations for clinical trials.
Adverse Events
It is possible that you have to provide a copy of any correspondence regarding safety information (including SAE submissions) between you and the competent health authorities to the pharmaceutical company’s drug safety department. Furthermore, it is not unusual that there exists a specific time period for reporting and for creating periodic information reports.
see 19
Pharmacovigilance
Early Termination
You must be aware, that for some reasons, the study may be stopped prior to its conclusion. The pharmaceutical company could reserve the right to terminate the agreement (e.g. in the event of irregularities in the method by which the study is carried out, or, if necessary, in the interests of the health of the trial subjects).
Moreover, a further clause should imply that the company compensates you pro-rata if the study is unilaterally terminated earlier than this agreement, or if you are unable to complete the study for reasons beyond your control.
Drug Usage
The pharmaceutical company must agree to provide the sponsor-investigator with the required units of drug, with the corresponding dosage for the number of clinical subjects.
Publication of Data
In this part, you may have the requirement that it is not allowed to publish or disclose information concerning the trial to any third party without the express written permission of the drug company.
Exclusion of Liability
The pharmaceutical company is not liable for a misapplication of the drug by the study participants. However, the liability for the quality, any defect in the manufacture, or the failure of the drug to meet product specifications will remain with the company.
Indemnity
You may use the following text directly in your contract:
In consideration of the sponsor-investigator entering into the agreement, the pharmaceutical company undertakes to indemnify and keep indemnified, the sponsor-investigator (‘the one whose indemnified’) from and against any loss, damage, reasonable expense (including reasonable legal costs and expenses) or legal liability (‘loss’) suffered or incurred by the one whose indemnified, arising from any claims or proceedings made or brought against the one whose indemnified and directly caused by an unlawful, wrongful, fraudulent or negligent act or omission of the pharmaceutical company, or any company personnel in connection with the study.
Insurance
You have to ensure that all necessary insurance required in order to perform the study are in existence and valid. Furthermore, you have to provide the company with a copy of the relevant insurance policy and to communicate any changes of the relevant insurance coverage with the company.
see 12
Insurance
Finance
For the conduct of the clinical trial, the pharmaceutical company may provide financial support for the total or for a specific amount. Also, an agreed schedule for the payment with the payee and address with a time frame for the payment should be listed in the Study Protocol.
see 6
Financing
Execution
Optionally, the contract can include an ‘entire agreement’ statement, such as the following:
This agreement constitutes the entire agreement between the parties with respect to this subject matter and supersedes all previous proposals, both oral and written, negotiations, representations, commitments, writings, and all other communications between the parties. This agreement may not be released, discharged or modified except by an instrument signed by the parties.
