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Hello dear youtube users, my name is Akcan AKKAYA and I would like to share a presentation with you, I am a physician, My topic is anesthesia & reanimation., I am an academician at a state university., And the subject of the topic that, I will share with you is clinical trial registry databases. , Our target audience will be academicians and researchers,, especially those who are new to the subject, We have been expected for a long time to register our clinical studies in a clinical trial registry database before enrollment of the first subject. , I will also post a presentation on this subject that I presented in a national course on youtube with the permission of the course directors., Because I observed that Turkish resources on this subject are few., Let's move on to our presentation now., First, let's make a definition., The definition I got from WHO is: All researches those examines the health outcomes of one or more, health-related practices by involving human participants or groups in the study. , It is included in the scope of a clinical study. , In other words, whether it is a drug, any surgical method,, or a psychosocial experiment, , If you get an output on human subjects., it is a clinical study and these must be recorded., Here, , the definition of the American ministry of health or NIH is a little, different, I want to summarize the presentation flow here, Its history, The interest of the International Association of Medical Journal Editors (ICMJE) on the subject., Then WHO's regulations on the subject., Then the situation in our country., Even after looking for an answer why we should register., I will conclude the presentation by referring to how to open a sample registration at clinicaltrials.gov., This issue was brought up for the first time with a law in the USA in 1988., The English name of the law is "Health Omnibus Programs Extension Act of 1988"., This is a law that specifically obliges the registration of clinical trials related to AIDS., At this point, the first website opened is "www.actis.org",, which is an abbreviation of the phrase "AIDS Clinical Trials Information System"., It has a beautiful story too., And I will share this story with you now., AIDS groups, of course, are mostly gay., This issue comes to the fore at their request., Then, rare disease groups, cancer, breast cancer-related ones also put forward their demands., After all, this business is growing., Of course, his name changes as he grows up., There is a transition from actis.org to clinicaltrials.gov., There is a very good movie about this process., Maybe you watched it., Original title of the movie: "Dallas buyers club", , nominated for 6 Oscars., Very well-known actors and actresses take part., We see Matthew McConaughey,, Jared Leto and Jennifer Garner in the lead roles., Here he plays a cowboy named Ron Woodroof, M.McConaughey., He is a gay-hating personality who prides himself on his masculinity., He lives a very different life and is diagnosed with AIDS at an unexpected moment in this life., He is said to live for 30 days., He reluctantly comes together with the gay community and starts selling drugs to them., He imports drugs from abroad., Of course, since he cannot sell them directly, he distributes them for free under the name of the club., The patient, who is said to live for 30 days, lives for 3 years., In these 3 years, he has been fighting a legal battle with the FDA and the American Ministry of Health., It's a long movie., I've watched it more than 2 times, I recommend it, of course, it's a movie in the adult category., The relevance of the movie to the subject is not my ascription., The film's relevance to the subject has been recorded, its IMDB score is 8 and it has a real-life quote., Years later, in an article in JAMA in 2014, the issue was defined as follows: , The laws that laid the groundwork for the establishment of Clinicaltrials.gov. were called "right to try" laws., After the movie, these laws started to be called "Dallas buyers club" laws., The movie enters the literature., Yes, the initiative that started in 1997 with the involvement of cancer and rare disease groups:, With the establishment of clinicaltrials.gov on February 29, 2000, it is now taking its final form., At first, there are state and private sector supported studies., The purpose of the tested drug, the eligibility criteria for the study, and the geographical areas of the study are visible in the records., Patients can submit their requests to the system., In 2005 ICMJE takes a decision and recommends that all studies be registered here., Authors are required to register their studies with clinicaltrials.gov before uploading the study to the journal., But in 2007 they make it mandatory., So, just because it has become mandatory, does it apply immediately?, Let's look at a study done 10 years later:, In a study done between 2010 and 2015:, 6869 original reports are examined., It is observed that almost all of them have been recorded, except for about 10%., Of these, 77% were registered prospectively and 23% retrospectively., Clinicaltrials.gov also allows retrospective registration of a completed study., However, ICMJE requires you to complete this enrollment process before enrolling the first patient., Here is another article on the subject., Here we see the emphasis that the registration process must have been completed before the first patient took part in the study., Retrospective records are still common in our country, with the editor's reminder., But I believe that in the future, the registration process will be completed before the first patient is accepted to the study in our country., Look how many journals are registered with ICMJE., You will also see magazines from our country, flowing in alphabetical order., Therefore, if you are going to make an ambitious publication, it is of great benefit to register your work here., What is the situation in our country? Is it mandatory in our country?, In our country, we see this issue especially in ethics committee guidelines., In the directive named "Ethics Committee Standard Operating Method Principles", there is an emphasis on the Declaration of Helsinki in the purpose section., There are also 2 times., You submit your application by approving the Declaration of Helsinki in many ethics committees., Then if you signed it, we need to know its contents as well., Look, these declarations, which came to the agenda with the regular meetings of the World Medical Association, which started in Helsinki for the first time in 1964, include the following provisions., In the declaration, which was last updated in 2013, it says in article 35:, 35. Every research study involving human subjects must be registered in a publicly accessible database before recruitment of the first subject., In other words, before the first patient is included in the study, there is a sanction emphasized with the "must be" mood, that all studies must be registered in a database accessible to the public., In short, if you sign the Declaration of Helsinki to the ethics committee in Turkey, you accept the aforementioned registration requirement., Then WHO becomes interested in the subject and sees the benefits of it., WHO says yes clinicaltrials.gov was created by the United States, followed by Europe and other countries., WHO at a meeting held in Mexico City in 2004:, Announces the need for a portal to enable simultaneous research among these databases., To this end, it establishes the International Clinical Trials Registry Platform (ICTRP) research portal, which can jointly search international databases., You can scan the databases specified at the bottom through the web page you see on the screen., So, which registry systems does the ICMJE approve?, It accepts all those who enter the WHO's portal..., There is a scientific concept called Preregistration., It is a concept that partially covers the clinical trial registration system, but it is not exactly the same., To avoid confusion, I will talk about this with a single slide here., Preregistration includes an approach that covers all sciences, whether engineering, biology, social sciences., Preregistration is the process of recording your hypothesis, method, and analysis before conducting a research., It is a pre-registration system that will be used for broad purposes such as consulting the scientific community and getting advice., There are literatures that suggest that scientific publications to be made in this way will be more productive., This concept partially covers clinical trial registration, but is a much broader concept. I have addressed the issue here to avoid confusion., On this slide you see clinical trial registry databases registered with WHO., We have many countries including Australia, Brazil, China, South Korea, Cuba, German, Europe, Iran, Lebanese, Thai, almost Srilanka., We would like to see our country too., There is a very useful association in our country called the Clinical Studies Association., It has a portal., In this portal, you can browse the studies originating in our country available on Clinicaltrials.gov., You do not log in to register here, you just scan the studies. Again, the medicine and pharmacy unit of the ministry of health has a clinical research portal., Here, too, both citizens and researchers can review current research., If you want to register your research here, you are directed to the relevant page., There is also an e-government(E-devlet sistemi) login on this page. I wanted to register from this link, but it did not work, the system required company support., It can be used for company-sponsored research, but unfortunately it is closed to individual research., I hope it will be recorded in individual studies in the future., Now let's talk about the benefits of clinical trial databases., Why should we register our clinical trial?, The primary benefit is observed in publication bias (Publication Bias)., In general, meaningful results are published in journals, and both editors and authors choose to publish results that are found useful and meaningful., Research whose results are found to be scientifically meaningless is often thrown away., However, these are the dead ends of the science labyrinth and it is important not to waste time and fulfilled works., Access and accessibility should be ensured so that the work done is not wasted., Clinical trial registry databases primarily serve this work., In other words, you can also find studies that are not worth publishing in the database., Another important benefit is to ensure the transparency of the clinical study., Provision of Tranparency. What is this?, Before a study, an idea is created., Then the protocol and method are determined., At this point, the protocols are recorded in the database and made available to stakeholders., A summary of the results is then entered., It is being made into a scientific publication., Afterwards, access to all data is provided., We call this process transparency., The first blue part in the picture is the phases you will use while registering to the database., At this stage, you register your work and the database registers your work with a unique number., With this registration number you will obtain, you can send your work to one of the journals registered with ICMJE., However, even if you get the number and have your work published, the database will ask you to enter your results into the system., While this important "CT.gov" does not currently require patient data for records from outside the United States, it is likely to become mandatory in the future., What are the other benefits?, Fulfilling ethical requirements for the research community and participants., The fact that the decisions of the ethics committee are open to the international scientific community increases the sensitivity of the decisions., The ethical values you use in your scientific work will be in front of the whole world., To enlighten potential participants and the clinicians who will guide them., Yes, just like the request of patients with AIDS, which we mentioned at the beginning, it, provides an opportunity both for you to reach the subjects and for potential subject patients to take an early role in a study if they wish., In addition, other clinicians have the opportunity to observe and follow your work., It is important here that the journal editors can observe the results and methodology of the studies., In fact, it should be emphasized that meta-analyses can be made much more successful if raw data are shared., There's also another benefit for journal editors to watch it:, We've experienced it at our university., If you have planned a successful study and this has been noticed and appreciated by the editors, you may encounter an offer to publish your research in a valuable journal before it is finished., In this way, both the resource providers and the research community will benefit., Now let's look for an answer to the question of how to register a study on CT.gov with an example., Primarily, CT.gov's home page is designed for patients and those who will review research., You can browse the research you are interested in by entering certain parameters on this page., These studies may be ongoing or finished in the past., In order to register your own work, you need to switch to another login page called PRS., Protocol Registration and Results System (PRS), For this, you go to the submit studies menu., From the menu that opens, you click on the "How to apply for an account" or "How to register your study" tabs., If you do not have an account, you can proceed to the 1st, if you have an account, you can continue to the 2nd., If you are going to apply for an account, you can check from the list whether the institution you work for already has an account., Even if you do not have an educational institution in the list, you can make an application for your institution by clicking on the link painted on the screen., You can complete your application with the official request of your institution representative or dean via this link., With this application, your institution will have an account and a person determined by your institution will be appointed as an admin., If there is an institution on the list, it will be at the addresses where you can reach the authorized person and that person is the authorized person who will open an account for you., Again, you can reach your institution representative from the page opened by clicking on the hypertext displayed on the screen and enter the necessary information to open an account., For example, when the form on the screen is filled in at my university, the request is sent directly to me., After receiving the username and password I assigned to the researchers, I continue to guide them while entering their studies., If you clicked on the "How to Register Your Study" hyperlink., Here you click on the "Login to ClinicalTrials.gov PRS" hyperlink in the lower left corner., It asks for the name of the day of the week, doing this to see if you're likely a robot., A 3-digit form will appear in front of you, where user name, organization name and password will be entered., The area you see on the screen is the home page where we will save our work., Here we click on the "new record" hyperlink., At this point, I recommend reading the "Quick Start" document., An artificial intelligence supervisor on the system roughly checks the information you entered, examines the errors and sends warnings., Here, 3 types of warnings are sent to you as ERROR, WARNING and NOTE. - ERROR, WARNING and INFORMATION NOTE, ERROR and WARNING are red, and INFORMATION NOTES are blue., If there is a red warning, the final progress button is not active. It becomes unusable., Blue notes, on the other hand, are suggestions and recommendations., You can continue with the installation process by taking the messages into account., This process is actually a bit like uploading an article to a journal., But the difference here is that only ethics committee information and material method section are required., In short, if you have finished your article in English until the end of the title, summary and method, your work will be very easy., It is also useful to purify your English from a site such as grammerly or textcheck., If you have followed these suggestions, the rest will be easy., If you are going to use this recording system extensively in the future., Then I suggest you to read the tutorials from the page on the screen., https://prsinfo.clinicaltrials.gov/tutorial/content/index.html#/lessons/, aRKE5uCiBRVSEP6gaInAOl1OXMEL93fw, https://l24.im/c9Ce0H shortlink, There are 7-8 pages of easy-to-read pdf files for each topic on this page., You can see it here., There are about 27 pdf documents and they give very descriptive information., Let's list the entry steps here., Study Identification: The ID of your study., Study Status: Status, Sponsor/Collaborators: Sponsors, Oversight: Relationship with FDA., Study Description: Definition, Conditions: Health issues of concern, Study Design: Methodology, design of the study, Arms/Groups and Interventions: If the study has comparison groups., Outcome Measures: Outcomes of the study., Eligibility: Eligibility criteria of participants., Contacts/Locations: Work location and contact information., IPD Sharing Statement: Whether to share personal patient data., References: References of the work., You can get offers from A-class journals before your work is finished, and having references can increase this probability., When logging into the system, we first see a fictional protocol number box that you will give yourself., Here you assign an arbitrary number to represent your work in an organization of 30 alphanumeric characters., My suggestion is the abbreviation of the institution, the abbreviation of the department, and finally the abbreviation of the principal investigator name and 001 added to it., Each line marked with red on this page is a mandatory line, the blue ones are optional., Acronym: We can say that they are nicknames given to some very great works to be memorable., Most personal works will not be Acronym., You must enter the type of Study. Is it interventional? Is it observational? Is it wide access? you must specify this., A large-scale research activity on drugs or devices is being questioned in wide access., In personal studies, more interventional and observational options will be preferred., When you fill them, the continue button becomes active and you continue by pressing it., On this page, in the status section, you are questioned about your position at the point of enrolling your patients into the study., Here are a few of the options., "Not yet recruiting" means that patients have not been recruited yet., When you choose "Recruiting", it means that you have included a few cases before submitting your application., Journal editors can comment on this., The options in this window are important because ICMJE requires you to complete your application before enrolling the first patient., Options such as not yet recruiting, enrolling by invitation may be more acceptable for editors., In other options, the editors will not accept it., There are 2 important end dates, the start and end dates of the study., One is the period when your primary outputs are closed and the date you recorded the last data., The "Responsible Party" option is important, you choose who has the right to fill in, approve and submit this application for evaluation., The "Priciple Investigator" option indicates that you, the primary investigator, is responsible, the "sponsor" option indicates that an institution is responsible, and the "sponsor investigator" indicates that one of the researchers is responsible., The relationship of your work with the FDA, if any, in the Oversight department is questioned and your ethics committee approval is requested., We enter the ethics committee information completely and in detail., Since the data monitoring section is not in individual studies in our country, we choose "No" here., But if the ethics committee is following your work, you should choose "yes"., In the "Study Description" section, you enter the summary of the study in the first box and the details in the second box., In the next section, you enter the diseases you are investigating., However, you need to get the description of these conditions and diseases from the NLM-MeSH database., National Library of Medicine's Medical Subject Headings (MeSH) National Library of Medicine Medical Subject Headings (MeSH) When, you click on the link in the figure, you can open the relevant page and search., Let's explain with an example, if you are looking for coronary artery disease, for example, you will copy the correct spelling from this search engine., You enter your study design here, Treatment: One or more interventions are being evaluated to treat a disease, syndrome, or condition., Prevention: One or more interventions are being evaluated to prevent the development of a particular disease or health condition., Diagnostic: One or more interventions are being evaluated to identify a disease or health condition., Supportive care: One or more interventions are evaluated to maximize comfort, minimize side effects, or mitigate against a decline in the participant's health or function., Screening: Evaluation or examination of one or more interventions in people who are not yet known to have the condition or risk factor, to identify a condition or risk factors for a condition., Health Services Research: One or more interventions to evaluate the delivery, processes, management, organization or financing of health services., Basic Science: One or more interventions to study the underlying mechanism of action (for example, the physiology or biomechanics of an intervention)., Device Feasibility: The response of a device product is evaluated in a small clinical trial (usually less than 10 participants) to determine the feasibility of the product; or a clinical trial to test a prototype device for feasibility and not for health outcomes., You are entering the phase of the study., Here, we will often choose phase 4, lower-level studies require ministry permission., If you have a benchmarking model, you will describe it in this option., Single group, parallel?, crossover?, factorial?, Is it in order?, You specify them., We usually have parallel or sequential group work., You enter the arms of research. Which methods and which groups?, If there is a randomization, you mark it and its shape., If you have applied blinding, that is, masking, you specify it and its shape., You detail the arms of the work., You need to indicate the arms of the work in a cross-reference chart., Then you need to enter your outputs., Most correction requests come in the output section., Let's explain with an example., First you must define primary and secondary outputs., For example, if you measure blood pressure at 10 different time points, you define each one separately as a primary output., I should emphasize this here. While calculating the sample size at the beginning of your research, the values you use are your primary outputs, you should consider this., We can also call it the "time frame" measurement range. You are asked to describe and note down each time interval measurement as if it were a separate output., Let's explain with an example, you can see the before and after correction., In this slide, the top sentence is wrong version but on the bottom 2 lines is correct., Then you need to enter your eligibility criteria., Finally, your contact information is being questioned., "IPD sharing" is questioning whether you will share the personal data of patients. Entering references is optional., If you have entered all of them almost exactly, you will see a green "arrow" sign on all lines., The blue notes are not a hindrance, but they mean it's worth checking out., Now the "Entry Conplete" button is active and you can send it for review by pressing it., If you did not choose "Priciple Investigator" in the Responsable Party section at first, I also receive completed entry of a study for checking at my university and start the release/approve process.(If the responsible party is the universty), If there is no correction, a number is assigned to the work and a response is made., However, if there are red "errors" and "warnings" when you complete the login process, you can't proceed any further, you need to fix them., If successfully logged in and confirmed., The number you see here is given to you and you can apply to the editor of the journal you plan to publish with this number., Of course, the editor can enter the system with this number and compare your work here and the version you sent to him., But it doesn't end just because you actually got a number., The red warning flag you see here is a warning to enter the results of the study on the specified date., In short, even though our study has been published, our responsibilities to CT.gov continue., Thank you, you can write your questions in the comments section.