STANDART OPERATING PROCEDURES
(Objective, Scope, Responsibility, Definitions, Procedures)
1. OBJECTIVE: The purpose of this standart operating procedures (SOP) is to define the process from the initial application to the closure of the clinical trials that will be held at the Faculty of Medicine, Ege University.
2. SCOPE:This SOP covers the activities of Ege University Faculty of Medicine Project and Special Services Coordination Center (PSSCC), Sponsors, Contracted Research Organizations (CRO), principal/subinvestigators and all parties participating in the clinical trial.
3. RESPONSIBILITY: Ege University Faculty of Medicine PSSCC employees, Sponsor, Contracted Research Organization (CRO), principal/subinvestigators and employees participating in the clinical trial are responsible for the implementation of this SOP.
4. DEFINITIONS
4.1. Clinical trial: Any investigation in human subjects intended to discover or verify the clinical, pharmacological and/or other pharmacodynamic effects of an investigational product(s), and/or to identify any adverse reactions to an investigational product(s), and/or to study absorption, distribution, metabolism, and excretion of an investigational product(s) with the object of ascertaining its safety and/or efficacy.
4.2. Principle investigator: A person responsible for the conduct of the clinical trial at a trial site. If a trial is conducted by a team of individuals at a trial site, the investigator is the responsible leader of the team and may be called the principal investigator.
4.3. Subinvestigator: Any individual member of the clinical trial team designated and supervised by the investigator at a trial site to perform critical trial-related procedures and/or to make important trial-related decisions (e.g., associates, residents, research fellows).
4.4. Sponsor: An individual, company, institution, or organization which takes responsibility for the initiation, management, and/or financing of a clinical trial.
4.5. Contract research organization (CRO): A person or an organization (commercial, academic, or other) contracted by the Sponsor to perform one or more of a sponsor’s trial-related duties and functions.
4.6. Good clinical practice: A standard for the design, conduct, performance, monitoring, auditing, recording, analyses, and reporting of clinical trials that provides assurance that the data and reported results are credible and accurate, and that the rights, integrity, and confidentiality of trial subjects are protected. Good clinical practice should be followed by all parties related to clinical trials.
4.7. Contract: A written, dated, and signed agreement between two or more involved parties that sets out any arrangements on delegation and distribution of tasks and obligations and, if appropriate, on financial matters. The protocol may serve as the basis of a contract
5. INSTRUCTIONS
Studies conducted at Ege University Faculty of Medicine are classified as “Clinical Trials Funded by Industry” and “Clinical Trials Funded by Govermental Sources”.
5.1. Clinical trials funded by industry
5.1.1. Application procedures
All phases of clinical trials, observational studies, medical device studies, studies within the scope of the early access program and studies financed by the Scientific Research Fund of Ege University start after completing the approval process of the budget followed by PSSCC.
The Sponsor, the CRO or the Principle Investigator should prepare and sign the following documents while applying to Ethics Committee approval simultaneously at the beginning of the study and apply online to PSSCC for the review of the trial.
The Clinical Trials Management System (CTMS) is a software used in the application and monitoring of all clinical studies conducted at Ege University Faculty of Medicine. CTMS enables all parties to transparently access information about their research, to monitor the application and approval process, and to follow all financial issues related to the conduct of the trial. All applications to PSSCC should be performed through CTMS.
Documents to be included in the clinical trials application file;
a) Protocol
b) Contract
c) Ege University Faculty of Medicine Clinical Research Budget Form
d) Application for the approval to receive payment from the Revolving Fund by taking advantage of the R&D incentive law
e) Request forms of laboratory tests and procedures to be carried out in our hospital for the clinical trial
f) Research cachet
g) Receipt of the file evaluation fee
h) Committee application file or if available Ethics Committee approval
i) Approval of the Ministry of Health for clinical study required by the legislation
j) Ege University Health Related Projects Supplementary Agreement
Equipment, drugs and any materials that will be supplied in kind to our hospital for use within the scope of the clinical study should be notified in the Clinical Research Budget Form.
* Note: This process should also be followed by the clinical studies supported by institutions such as TÜBİTAK (The Scientific and Technological Research Council of Turkey) and BAP (University Research Fund) or various foundations/associations and where a fee should be paid to the Revolving Fund Management Directorate for the procedures performed in our hospital.
The documents in the clinical trial application files submitted to PSSCC are examined and prepared to be submitted to the commission. The research contract, research protocol and budget of all clinical trial files submitted to PSSCC commission are evaluated by the Commission. Opinions and suggestions about the clinical studies are provided by the Commission.
The PSSCC Commission preferably consists of at least seven faculty members, Coordinators and Sub-unit Supervisor faculty members appointed for three years from the Internal and Surgical Sciences and Pediatrics. The Head of the Center chairs the Commission.
After the Commission evaluation, the missing documents that may prevent the patient recruitment are requested to be completed in a short time and the study is started after the completion of all requirements suggested by the Commission.
5.1.2. Approval process
The approval phase begins for the files whose budget and eligibility are determined after the examination is completed by PSSCC. The original of the approved contract, Ethics Committee Approval, Ministry of Health Approval documents for studies that require approval from the Ministry of Health are submitted to PSSCC for signing the contract.
5.1.3. Clinical trial initiation process
An original signed copy of the contract and Ege University Faculty of Medicine Hospital Clinical Research Budget Form (original signed by principal investigator and Sponsor) and Ege University Health Related Projects Supplementary Agreement are delivered to PSSCC.
PROKOM defines the study code in the Hospital Information Management System (HIMS) and an official letter for notification is sent to the principle investigator in the relevant Department/Subdivision.
The principle investigator contacts the Information Technologies Unit, and it is ensured that the personnel in charge of entering clinical trial related facilities are trained.
All procedures related to the clinical trial should be done by using the research code, and services other than the work should not be entered from this code. According to the legislation, it is forbidden to bill the services provided within the scope of the clinical trial to the Social Security Service (SSS) to which the volunteer is affiliated.
The principal investigator is responsible for checking and correcting all procedures (examination, examination, treatment and attempts, material, medicine, etc.) specified in the contract related to the clinical trial and ensuring that they are defined in HIMS through the research code.
Within the scope of the research, all financial liabilities that may arise if/when the procedures are invoiced to the SSS of the volunteer enrolled in the clinical trial belong to the responsible researcher.
The Sponsor is obliged to pay all of the service items accrued under the research code.
5.1.4. Payment and invoicing process
Payments required by the Institution should be made in accordance with the schedule specified in the contract.
Complying with the payment terms specified in the contract; Sponsor/CRO applies to the Hospital Registry Office with a request letter related to whole expenses. Attached to the request letter, the documents including protocol numbers of the volunteers enrolled in the data collection system until the date of payment, clinical trial dates and details must be signed by the principal investigator.
The accrual list in the HIMS (research code, SSS entry etc.) of the documents mentioned in the request letter and the study period is prepared by PSSCC and sent to the Sponsor/CRO for the required controls and corrections.
The accrual list checked, approved and signed by the Sponsor/CRO is sent to the Billing Unit in order to initiate the invoicing process. However, if there are services invoiced to SSI during the control process, receipt of these services should also be forwarded to the Invoicing Unit and PSSCC as well
Protocol number of the research, names of the principal investigator and all researchers to be paid, and payment items should be specified in the payment receipts delivered to Ege University Faculty of Medicine. In the payment items, the amount of payments should be specified separately for the investigators’ fee and for the service received from our hospital.
Invoices are issued after the payment receipts are sent to PSSCC and Revolving Fund Management Directorate. Invoices for procurement of services and invoices for the investigators’ fee are issued by the Revolving Fund Management Directorate.
Charges of healthcare services included in Clinical Trials and Projects; charges of Healthcare Service fees are determined as 5 times the prices in the Public Service Price List, and the charges of the transactions not included in the Public Service Price List and its annexes are invoiced by adding 50% of the transaction charge included in the Health Implementation Notification.
5.1.5. Protocol, budget, contract changes, extension processes
In case of a change in the budget, protocol and/or contract, the Sponsor/CRO submits the reason for the change, the Ethics Committee's Approval and the Ministry of Health's Approval (if required again by legistlation) to PSSCC for the signing of the amended contract. Examination and approval processes are carried out as specified in Section 2 and 3.
5.1.6. Closing/ termination of studies
When/if the clinical trial is expired and/or completed or terminated for any reason (including those not recruited any volunteers) or patient recruitment in the trial is completed, the Sponsor/CRO applies to PSSCC with a petition stating that the study will be closed and payments have been made. A copy of all payments and/or in-cash records made to the Revolving Fund Management Directorate must be attached to the notification that the study has been closed.
PSSCC finalizes the required control of payments and ensures the closure of the study code defined in the HIMS as of the date of the notification. This procedure results in the prevention of addition of any new transactions in the clinical trial.
5.1.7. Key issues to consider
It should be stated in the contract that any costs for serious adverse events arising in connection with the trial will be borne by the Sponsor.
Hospitals are exempted from Value Added Tax in accordance with the provisions of Article 17 titled "Other Exceptions for Social and Military Purposes" of the Value Added Tax Law No. 3065. Therefore, any taxes, duties, fees, etc. Ege University Medical Faculty Hospital will not be the contractor for the payments.
All of the records related to the research are kept regularly by the Sponsor and the researcher. These records are kept for at least fifteen years for studies with active implantable medical devices, and for at least five years for studies with medical devices, after the study is completed in all centers.
In case the principal investigator changes with any reason, Sponso/CRO reports the change to the Ethics Committee and the Institution. Institution informs the Department/Subdivision of the principal investigator and the eligibility for new principal investigator is determined by the Department/Subdivision. In this case, an amendment of contract should be prepared.
If/when the Sponsor/CRO changes in the clinical trial, an amendment of contract should also be prepared after the approval of the Ministry of Health. In case of the transfer of the research to a new Sponsor/CRO, archiving of trial-related information and documents should be done by the new Sponsor/CRO in accordance with the relevant guidelines. Confidentiality of research-related documents is essential. These documents are given to authorized persons only at the request of legally authorized persons or authorities.
5.2. Clinical trials funded by govermental sources
In the clinical trials funded either by governmental sources (i.e. TÜBİTAK-The Scientific and Technological Research Council of Turkey or BAP-University Research Fund) or by the academic staff themselves, the principal investigator should apply to PSSCC by indicating the number of all procedures related to the trial (i.e. physical examination, laboratory tests, treatments and operations)
Documents to be included in the application file of clinical trials funded by the governmental sources;
a) Protocol
b) Ege University Faculty of Medicine Clinical Research Budget Form
c) Request forms of laboratory tests and procedures to be carried out in our hospital for the clinical trial
d) Research cachet
e) Ethics Committee application file or if available Ethics Committee approval
f) Approval of the Ministry of Health for clinical study required by the legislation
The charges of the Health Implementation Notification Per Service Procedure Score List / Annex-2B prices are taken as a basis for charging the procedures in academic studies supported by governmental sources (TÜBİTAK, BAP etc.) or the academic staff themselves (invoice is made on behalf of the academic staff), and the charges of the Health Implementation Notification are used for charging the drugs and medical consumables.
All other clinical trial procedures are performed similarly to Clinical Trials Funded by Industry.
6. Related Legislation
6.1. Regulation on Clinical Trials of Pharmaceuticals and Biological Products, Ministry of Health Turkish Medicines and Medical Devices Agency is published in the Official Gazette numbered 28617 and date13 April 2013 ( The link is in Turkish)
6.2. Law No. 3065 on the Value Added Tax is published in the in the Official Gazette numbered 18563 and date 20 November 1984 ( The link is in Turkish)
6.3. Regulation on the Establishment of Higher Education Institutions Revolving Funds, in the Official Gazette numbered 31159 and date 18 June 2020 ( The link is in Turkish)
