INFORMATION FOR INVESTIGATORS

CONTENTS

1. What is a Clinical Trial?

2. Who Conducts Clinical Trials?

3. Who Funds Clinical Trials?

4. Where are Clinical Trials Conducted?

5. Who Can Participate in a Clinical Trial?

6. How are Volunteers Protected?

7. How are Volunteers Informed?

8. What are the Phases of a Clinical Trial?

9. Which Institution Needs Approval for Clinical Trials to be Conducted?

10. What are the Regulations Regarding Clinical Trials in Our Country?

11. Where Can I Access Application Forms Related to Clinical Trials?

12. Why should the Clinical Trials and Their Results be Registered in the World and in Turkey?

13. What are the National and International Web Sites/Databases Related to Clinical Trials?

1. What is a Clinical Trial?

A clinical trial is 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. The terms “clinical trial” and “clinical study” are synonymous.

2. Who Conducts Clinical Trials?

A clinical trial is conducted at a trial site by a team of individuals with sufficient training and experience in accordance with the nature of the research under the leadership of the principal investigator. The principal investigator is the physician or dentist who has completed the specialization or doctorate education in the field related to the research and is the responsible leader of the team. Subinvestigator is any individual member of the clinical trial team designated and supervised by the principal 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) The principal investigator and the subinvestigators should be fully informed and comply with Good Clinical Practices (GCP), the current Declaration of Helsinki and relevant legislation.

3. Who Funds Clinical Trials?

Clinical trials are supported by pharmaceutical companies or national health institutes or research supporting institutions (such as the Scientific and Technological Research Council of Turkey, Presidency of Turkey Health Institutes) and other organizations. Physicians and other healthcare providers may also sponsor clinical trials.

4. Where are Clinical Trials Conducted?

Clinical trials can be conducted in faculties of medicine, training and research hospitals, research and development centers affiliated with universities, and preferably in places designed for clinical trials and approved by the Ministry of Health. A clinical trial site should have personnel, equipment and laboratory facilities suitable for the research of interest ensuring the safety of the volunteers.

If/When necessary, other health institutions and organizations with the specified qualifications may be included in the clinical trials carried out in these centers and hospitals, provided that they are under the coordination or administrative responsibility of qualified centers and hospitals.

5. Who Can Participate in a Clinical Trial?

Volunteer patients or healthy individuals who meet the standards specified in the trial protocol can participate in a clinical trial with the written permission of themselves or their legal representatives.

6. How Are Volunteers Protected?

In order to conduct scientific research on humans and for the protection of the rights of volunteers,  clinical trials should be carried out in accordance with the guide of Good Clinical Practices (ICH-GCP) prepared within the framework of the European Union Standards and the Regulation of the Ministry of Health on Clinical Trials of Pharmaceuticals and Biological Products and in accordance with the related legislations and ethical principles.

Ethics Committees are independent committees established to provide scientific and ethical opinions about the research in order to ensure the rights, health, safety and well-being of the volunteers who will participate to the research. Studies can be carried out after the approval of the Ethics Committee and the Ministry of Health.

The candidate should know as much as possible about the study and should feel comfortable for asking any questions about the study to the research team.

7. How are Volunteers Informed?

Volunteer candidates are initially informed about the details of the trial.  For this purpose, the "Informed Consent" process is used. The informed consent process aims to inform participants, helping them understand the risks, potential benefits, and alternatives of the study.

If the volunteer agrees to participate in the study, they must sign a clinical trial-specific “informed consent form” to declare that they have been informed and have understood the risks, potential benefits, and alternative treatment options prior to participating in the trial.

Signing the document is not a contract.  Volunteers can leave the study at any time and without giving any reason, even if the study is not completed yet.

8. What are the Phases of a Clinical Trial?

There are different phases of drug clinical trials.

• Phase 0: Preclinical Studies; The drug is administered to laboratory animals and the animal response to the agent is investigated.
• Phase 1: The pharmacokinetic properties, toxicity, bioavailability and pharmacological effects of the drug are investigated in a small number of healthy volunteers.
• Phase 2: The effective dose limits, clinical efficacy, biological activity, benefit and safety of the drug are investigated in a small number of patients.
• Phase 3: Drugs are administered to a larger population. Its safety and efficacy are investigated compared to placebo or standart therapy.
• Phase 4: Medicines that pass the first 3 stages are licensed and enter the market. Every research performed after the legal approval by the authority belongs to phase 4.

In addition to phase studies, observational studies are also carried out on licensed drugs and medical devices that are routinely used in the market.

9. Which Institution Needs Approval for Clinical Trials to be Conducted?

In order to start a clinical trial, first the approval of the Ethics Committee and then the approval of the Turkish Medicines and Medical Devices Agency of the Ministry of Health is required.

Ethics Committees are independent committees established to provide scientific and ethical opinions on research in order to protect the rights, health, safety and well-being of the volunteers who will participate in the clinical trial.

10. What are the Regulations in Our Country Regarding Clinical Trials?

The following regulations have been published by the Turkish Pharmaceuticals and Medical Devices Agency regarding the products falling under its jurisdiction.

• Regulation on Clinical Trials of Pharmaceuticals and Biological Products
• Medical Device Clinical Research Regulations
• Regulation on Efficacy and Safety Studies and Clinical Researches of Cosmetic Products or Raw Materials
• Guidelines for Observational Drug Studies

11. Where Can I Access Application Forms Related to Clinical Trials?

The necessary information and application forms regarding clinical trials on treatment methods, medicinal products for human use (drugs) and products with health claims can be accessed on the website of the Turkish Medicines and Medical Devices Agency; with the exception of stem cell, organ tissue transplantation and traditional complementary medicine applications.

The necessary information and application forms regarding medical device research can be found on the Turkish Medicines and Medical Devices Agency website.

12. Why should be Registered Clinical Researches and their Results in the World and in Turkey?

In paragraph 36 of the Declaration of Helsinki it is stated that “Researchers have a duty to make publicly available the results of their research on human subjects and are accountable for the completeness and accuracy of their reports. Negative and inconclusive as well as positive results must be published or otherwise made publicly available”. The World Health Organization's (WHO) Statement on the Public Disclosure of Clinical Trial Results in 2015, it is stated that, "It is an ethical imperative to report all clinical trial results, including those that have not been reported in the past."

For this reason, databases have been created to record clinical trials when they start, to provide timely updates, to record the summary and results and to make this information available to the public.

Records contribute to medical knowledge and ensure that ethical obligations are fulfilled to participants and institutions participating in the clinical trial.

13. What are the National and International Web Sites/Databases Related to Clinical Trials?

1- Turkish Medicines and Medical Devices Agency. https://www.titck.gov.tr/

2- Clinical Trial Portal of the Turkish Ministry of Health: https://kap.titck.gov.tr/

3- National Clinical Trial Infrastructure Network Application and Research Center: https://tucrin.deu.edu.tr/tr

4- Turkish Pharmacological Society: http://www.tfd.org.tr

5- Clinical Research Association: http://www.klinikarastirmalar.org/

6- Association of Contracted Research Organization: http://www.sakder-tr.org

7- Association of Research-Based Pharmaceutical Companies : https://www.aifd.org.tr

8- The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use - ICH) : https://www.ich.org/

9- ClinicalTrials.gov: https://clinicaltrials.gov/

10- European Union Drug Regulating Authorities Clinical Trials- EudraCT https://eudract.ema.europa.eu/

11- Clinical Trials Registry Platform- ICTRP) https://www.who.int/clinical-trials-registry-platform

12- MedlinePlus® Online Information Service: https://medlineplus.gov/

13- Research Match-RM https://www.researchmatch.org/

14- Office for Human Research Protections- OHRP https://www.hhs.gov/ohrp/index.html

15- Share Investigator Platform- SIP https://sipidm.sharedinvestigator.com/

16- European Clinical Research Infrastructure Network- ECRIN) https://ecrin.org/