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How Clinical trial Works with help of SAS.

ABSTRACT: Clinical SAS® programmers come from diverse backgrounds. As programmers step into this new field, they would have enough working knowledge about SAS techniques and how to program tables, listings, and graphs. However, as in any other field, there are lots of everyday activities, terminologies, and processes that a programmer should be aware of in order to be successful and will learn on the job over a period of time, depending on the work environment.

This paper is primarily targeted at programmers who are relatively new to the field of clinical programming and the objective is to provide an early introduction to the various aspects of clinical programming. CLINICAL TRIALS By now, you must have heard about FDA and its consumer watchdog division, called CDER (Center for Drug Evaluation and Research), whose job is to evaluate new drugs before they are marketed. The process of development and approval of new drugs is generally complicated, expensive, and time-consuming and involves many scientists and professionals with varying expertise. Once a company identifies a compound as promising, a series of pre-clinical trials will be conducted and the results of those studies as well as future plans justifying clinical trials are submitted to the FDA. Upon approval from the agency, the company will start testing on humans.

Clinical Trials are well-controlled research studies of a new drug or device to answer scientific questions regarding the safety and efficacy of the drug that is being tested. They progress in a series of phases.

Phase I trials – These first-in-human studies are conducted on a small group of healthy volunteers or individuals with the target disease, to establish a dosage level and to study the safety profile.

Phase II trials – Intended to evaluate the effectiveness and to continue safety testing on individuals with the target disease, on a larger group of people.

 Phase III trials – To further obtain additional safety and efficacy data on a large group of demographically diverse populations. Usually, involves multiple trials conducted at many sites either nationwide or worldwide.

 Phase IV trials – These are long-term studies conducted after the drug has been approved and marketed. The purpose is to study the side effects a result of prolonged use.

As you can imagine, there will be an enormous amount of data that will be collected from all these clinical trials at various stages of development and stored in various databases. Clinical scientists and other team members need to obtain results and draw inferences from these studies - and that is where you come into the picture. Programmers extract the data from the database and present them in a condensed table form or print out all the details as a listing, or present them as a graph,

deemed necessary. This is put in a very simple way – in real life, it is a lot more complex and involves an extensive amount of work. The data that is collected during clinical trials are broadly grouped into either safety or efficacy. Safety data which includes adverse events, labs, vitals, etc. are collected to monitor the patient safety while participating in the clinical trials and has always been a primary focus in the development of new pharmaceutical products as it helps to relate the benefits to risk. Data collected to demonstrate the effectiveness of the investigational product are grouped under efficacy and statisticians will be primarily using this data to draw statistical inferences.

DOCUMENTS Once a programmer is assigned to work on a study, there are certain documents that need to be reviewed to gain a good understanding of the study design before starting to dig through the data. Among them, Study Protocol, Case Report Form (CRF), and Statistical Analysis Plan (SAP) or its equivalent are the most important. Study Protocol describes among other things, the way the study is designed, whether it is an open-label or blinded study, treatments assigned, the number of subjects, duration, visit schedule, etc. Since the study protocol is a reference document for the clinical trial, it will include a lot more detailed information than what a programmer is looking for.

It is worthwhile to spend time understanding the study protocol and it will help tremendously while coding. A CRF is a printed or electronic document designed to collect all protocol-required information on each subject in a clinical trial. This data will then be transferred into a database and will be made available to SAS programmers as ‘raw’ datasets. Annotating the CRFs with variable names will provide a link between the variables in the dataset and the fields on the form. In most companies, CRFs are annotated electronically since it is mandatory for the electronic submission of datasets to the agency.