Clinical Data Management: Basics for Freshers

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Clinical data management (CDM) is one of the most popular fields in clinical research. Many of the freshers and even experienced want to pursue clinical data management jobs. In the article on how to start a career in clinical data management, we discussed the groundwork and planning needed to start a career in CDM. Going forward, I will share the clinical data management basics to advanced CDM. This article will give you a free Clinical data management course. Before you read further, I recommend you to read about the history of clinical trials.

Insights

Let’s think, you are pursuing a PhD in Molecular pharmacology and your area of interest is breast cancer. During your research, you found a biomarker that can be used to target programmed T-cells to produce tumor-specific antibodies and also to enhance anti-tumor immunity. This will prevent healthy cells from killing and can prevent any specific drug-regulated adverse reactions. So you got results on this approach and want to pursue it further because the research shouldn’t die in labs.

Every researcher’s dream is to bring his research or the molecule he identified to the market and serve his purpose. The research you did is on animals and we call this method of research “Pre-Clinical Trials”. The data generated alone during the Pre-clinical is not sufficient to release your drug into the market. you have to perform human trials on the same approach. So you go to the sponsor with the animal data that is supporting your approach has a great impact on balancing the safety-to-efficacy ratios and if the sponsor agrees, he files for the Investigational new drug application (IND). Once it is approved by the regulatory authority, the journey of clinical trials begins.

Now you are skeptical of how the CDM basics and research are aligned? The role of CDM starts from the start of a clinical trial. Not only CDM, but even every field of clinical research also starts from the day the clinical trial is approved. To explain in-depth, I will give you an example of how different stakeholders in clinical trials are involved.

Example: After you identified the biomarker and decided to go further ahead of pre-clinical trials, you should start by applying for IND. The process of the IND application or any regulatory requirements is handed by Regulatory writing.

Adverse events and adverse drug reactions that are triggered from Phase I, till post-marketing surveillance are handled by Pharmacovigilance.

The handling of data during the clinical trials is handled by Clinical data management (CDM), the writing of clinical study reports is handled by a medical writer, and the writing related to publications, representing your drug information in conferences, etc will be handled by scientific writers and we also have clinical operations which include TMF experts, CRA’s, Investigators, site coordinators, etc.

These said stakeholders should work hand in hand to drive a clinical trial from its initiation to its completion, to drive a molecule from its birth to its release into the international markets. All these people should coordinate for the birth of every drug and to stand for purpose in treating patients, in giving them a better life. Every person who is working in a clinical trial is serving the purpose of every patient directly or indirectly. We are making a difference in their lives. We should feel proud to be part of clinical research.

Basics of Clinical Data Management (CDM)

Introduction to Clinical Data Management (CDM)

Let’s get back to the molecule you found during your research that can cure breast cancer. You applied for IND and you got the approval and now you can start with the Phase 1 Clinical trial. Before you go ahead, you should have the protocol ready. So what is protocol in a clinical trial? As per the University of California, Clinical trial Protocol is defined as follows:

THE PROTOCOL IS A DOCUMENT THAT DESCRIBES HOW A CLINICAL TRIAL WILL BE CONDUCTED (THE OBJECTIVE(S), DESIGN, METHODOLOGY, STATISTICAL CONSIDERATIONS, AND ORGANIZATION OF A CLINICAL TRIAL,) AND ENSURES THE SAFETY OF THE TRIAL SUBJECTS AND INTEGRITY OF THE DATA COLLECTED.

Once you have the clinical trial protocol is ready, it has to be approved by the Institutional Review boards (IRBs). The clinical trial protocol and procedures are tailored to fit generic IRB submission requirements. Every site or in a generic term clinical institution or a hospital where the clinical trial is performed will have their local IRB. So the protocol is submitted to the local IRBs and once it is approved, the sites can start recruiting the subjects for the clinical trial.

Once the protocol is approved, the process of Clinical data management comes into force. So what do clinical data managers or clinical data associates do after the protocols are approved?

I will give a simple example. Just think you got a fever and you got to a hospital to get diagnosed and then treated right? In clinical research terms, We call the patient “Subjects“, hospitals as “Clinical Sites“, doctors “Investigators“, Nurses or other staff “Site coordinators” and the person who oversees multiple sites and checks if all the clinical sites are working as per “Good Clinical Practices”, we call as “Clinical Research Associate or CRA“. Try to remember these terms as I will be using them frequently going forward.

Going back to the above example, when you go to a doctor for a fever. The doctor will check your vitals, and temperature and write it down in a case file. Also recommends you go to a lab and get the blood tested so that it will be easy for him to diagnose the problem. Once the lab results are generated, you take back those results to the doctor. He will check the results and prescribe the medications with a certain dosage regimen. If you see the whole process, there is some data generated. Just assume the amount of data that is generated in one clinical trial that will recruit around 6000-10000 patients for an average period of 10 years.

The data that is generated is so huge that you can’t store it in a book or simple Excel sheet. We need a database that is tamper-proof, standardized, and can be approved and used as per 21 CRF Part 11 guidelines. That is where clinical data management comes into the process. In CDM, we evaluate the protocol and as per the protocol, we design the database.

So in Clinical data management, the workflow is differentiated into three categories: Study Start-up, Study conduct, and Study close-out. I will explain briefly here and also explain the advanced structures and processes involved in each category of clinical data management: Study Start-up, Conduct, and Close-out.

Clinical Data Management (CDM): Study Start-up

In the clinical trial protocol, we have a section called “Visit Evaluation Schedule” or “VES”. This section tells you how different data is collected at different visits.

Once the subject is enrolled into a clinical trial, we take screening data which means, we collect his Demography, his history of medications, did he had any other diseases before, and other screening data as per your protocol.

Once he meets all the criteria of the clinical trial protocol, he can start taking the study medications or study drugs. So we have a schedule on how this study drug is taken on which day. Once the study drug is taken, we also have a schedule when the blood is collected from the patient to understand the Pharmacokinetic profiles, pharmacodynamic profiles, and other assessments.

This whole schedule is explained under VES. So CDMs use this VES to build the database. There are different databases available and it depends on the mode of collection of data. Previously, clinical research organizations or Pharmaceutical companies used to collect the data on paper. We call it as “Paper Case Report Form”. So Paper CRFs, these companies used to build clinical trial databases on Oracle Clinical, Open clinica etc. But these days, data is collected electronically on eCRFs and these companies are using EDC systems like Medidata Rave, OC RDC, Inform etc.

So the study start-up mainly involves, building the database and evaluation of the database through testing. So to keep it in simple terms, the study start-up in clinical data management includes clinical trial Protocol validation, CRF Design, Design, and validation of study documents, User acceptance testing of the database, Approval of the clinical database, and also the steps involved in Go-live of the clinical database. I will cover the most advanced part of the study start-up in a separate article. However, these terms are required to be explained during the interview of clinical data management jobs.

Clinical Data Management (CDM): Study Conduct

Once the clinical database is built, it will be released for use by different stakeholders: The clinical operations team, Clinical data management (CDM) team, Safety team, and other key stakeholders. The review of data that is added to the database will be mainly reviewed by the clinical data management.

What does CDM do with the updated data in the clinical database? We review the data to check for its clinical consistency. We try to find issues and ask the sites if they missed any critical data not entered as per the protocol. So who will tell the CDM on what data to review? It is the protocol. It’s the mother document that tells you all the answers to your questions. Once you are so confident about your protocol, reviewing data will be like a piece of cake.

If you see the above CDM process chart, the middlebox explains all the activities that happen in CDM conduct. I will explain the study conducted in detail in a separate article. The series of articles that I write on CDM will help you to crack an interview on Clinical data management Jobs.

Clinical Data Management (CDM): Study Close-out

Once the study enters the Last patient’s last visit, the study close-out process will take place. This is the time when the data manager has to make sure all the data is entered as per the clinical study protocol. The data manager has to ensure all the data that is entered is clean and solves the requirement of the clinical trial protocol. All the data that is received from third parties are reconciled and clean. Once the data manager gets the approval that sufficient data is collected and also all the stakeholders agree on the terms, the clinical data manager can go ahead with the study close-out.

What we do in study close-out. We just lock the study. Study lock means we remove the access for all the sites to disable the data entry. The final reports will be shared with the Statisticians to create the final interpretation of the clinical data in the form of tables, figures, and listing.

once the database is locked, the data is shared with Biostats to create TFLs and these TFLs will be used by the medical writers to create clinical study reports which will be submitted to the regulatory body for approval.