Understanding How Data is Collected in Clinical Trials
What are the methods used to ensure that data from AIDS vaccine trials are of high quality?
AIDS vaccine clinical trials depend upon a number of factors to be successful. The candidates undergoing testing must first submit to extensive pre-clinical evaluationÑinitially in the laboratory and later in animal modelsÑso researchers and regulators, who approve the clinical studies, can obtain essential information about whether the vaccine candidates are safe, and whether they demonstrate efficacy in animals. This can help predict how well they might work in people (see VAX October 2006 Primer on Understanding AIDS Vaccine Pre-Clinical Development).
AIDS vaccine trials must also follow Good Clinical Practice (GCP) guidelines, which are an international quality standard for conduct of clinical trials. Ethical and regulatory review committees from the countries and institutions that are involved in the clinical trial must provide approval for the trial before it can begin, and also provide guidelines for the trial staff (see VAX June 2005 Primer on Understanding Informed Consent).
In addition, external committees known as Data and Safety Monitoring Boards (DSMBs) or Safety Review Boards (SRBs), monitor the trial once it is underway (see VAX June 2007 Primer on Understanding Data Safety Monitoring Boards). The DSMB or SRB for a clinical trial evaluates the data regarding safety and efficacy that emerges from the trial while it is in process.
Collecting quality data is central to the mission and purpose of a clinical trial. Without consistent and unambiguous methods of data collection, researchers run the risk of conducting a trial that is unable to draw any firm conclusions about side effects, adverse events, or even whether the vaccine candidate is effective or not. Therefore, clinical trial sites continually work to make sure the process of data collection is as accurate as possible. Also, since many clinical trials are conducted at multiple centers, often in different countries and regions of the world, it is necessary for all data to be recorded consistently, so that it is comparable.
Collecting high-quality data starts with training the staff to properly collect and record information, both by hand and electronically. Usually, nurses, physicians, and counselors working on a clinical trial collect data from volunteers. During the screening process for a trial, nurses will conduct physical exams, HIV tests, and other baseline medical criteria from potential volunteers so there is a record of their general health before they are enrolled in the trial. Then, throughout the course of the trial, nurses, physicians, and counselors will collect additional data from all of the volunteers such as measuring and recording a volunteer’s vital signsÑgenerally their temperature, blood pressure, pulse, and respiratory rate.
Once volunteers in the trial have received vaccinations with either the vaccine candidate or placebo, nurses or physicians also examine volunteers for any potential adverse events, including fever, rash, or headaches. Periodic testing for HIV is also performed and all volunteers receive counseling about how to reduce their risk of HIV infection. The frequency at which this data is collected is defined in the trial protocol, which describes the objectives, design, methodology, and statistical considerations for the study. It is essential that all clinical research centers participating in a trial record data in consistent intervals of time.
These observations are all carefully recorded on what is known as a source documentÑa paper record kept for each volunteer with the observations made by the nurse, physician, or counselor.
Along with the source documents, staff at the vaccine research centers record data on electronic case report forms, which are transmitted to a data coordinating center for analysis by statisticians. It is important to use a common case report form so that all data is collected in exactly the same manner for each volunteer, and to ensure that the same standards are used to evaluate any possible adverse event. For instance, if clinical trial centers have different guidelines for what constitutes moderate or severe redness on the arm following inoculation, it may be difficult to conclude how to characterize the severity of this reaction at the conclusion of the trial. Although such observations are still subject to some level of human interpretation, clinical trial specialists try to control this as much as possible by creating standardized tools.
They also have built a series of checks and balances into the case report forms, which can help identify erroneous entriesÑsuch as an unusually high blood pressure of a trial volunteerÑand alert researchers to take a closer look. Additionally, the sponsors of a trial have monitors who compare the data on the source document with information on the case report forms to make sure the information is consistent.
Standardized case report forms become particularly important in large, Phase III trials where there are several thousand volunteers and hence drastically more data to analyze and compare. Since these large trials are also the final step of clinical evaluation prior to the candidate being considered for regulatory approval, it is essential that data regarding any adverse events or the efficacy of the candidate is recorded accurately and consistently since this information will influence regulatory considerations regarding licensure of the vaccine candidate for public use.