Introduction to Clinical Research: Part 1

New technologies are rapidly improving the way we diagnose and treat our patients. The clinical integration of these innovations would not be possible without the meticulous safety and efficacy testing they undergo in clinical research. Although subspecialties, such as dry eye disease, specialty contact lenses, myopia, and vision therapy, continue to gain recognition, involvement in clinical research remains unexplored by many optometrists.

Clinical research offers the rewarding benefit of actively contributing to advances in eye care through evidence-based practices. Fundamentally, clinical research involves the systematic investigation of diseases, their progression, and the efficacy of new treatment methods. Participation in clinical research also provides early exposure to the latest diagnostic innovations, treatment modalities, and therapeutics. Having participated in clinical research myself for more than 2 years, I have experienced all the above firsthand. I will be imparting my insights in this multi-part series, beginning with this article, which provides an overview of how to get involved in clinical trials and the benefits you can gain by doing so.

BE CONFIDENT IN YOUR SKILLS

As optometrists, our extensive training and clinical expertise has equipped us with the vast majority of skills required to conduct an ophthalmic clinical trial. We understand the intricacies of the ocular anatomy and the methods of subjectively and objectively evaluating ocular diseases sufficiently to design a clinical trial that produces accurate and meaningful data. The accuracy of ophthalmic clinical trial data depends on attention to detail and the detection of subtle changes in the eyes—skills that we refine daily through our patient care.

Becoming a clinical trial investigator offers various opportunities for professional and personal development. Clinical trial participation demonstrates to your patients your commitment to the advancement of eye care and to delivering the most state-of-the-art treatments available. Additionally, serving as a clinical trial investigator can garner recognition within the eye care industry, opening the door to potential leadership roles and networking opportunities.

The first step to becoming a clinical trial investigator is to familiarize yourself with the common terminology, the different entities involved with clinical trials, and the training and certifications required for the type of research in which you are interested.

TYPES OF CLINICAL TRIALS

Clinical trials originate from a sponsor company or an individual with a hypothesis and typically involve a medical device, pharmaceutical, or surgical procedure that has the potential to improve health care. The two primary types of clinical trials are sponsor-initiated and investigator-initiated.

Sponsor-Initiated

With sponsor-initiated trials, all aspects of the clinical trial, including its study design, regulatory approval requirements, funding, etc, are determined by the trial’s sponsor. Sponsor-initiated trials tend to offer a smoother entry into clinical research because the sponsor oversees most tasks outside of the actual scientific aspects of the trial; however, the sponsor typically has financial interest in some aspect of the clinical trial.

Investigator-Initiated

Investigator-initiated trials necessitate more clinical trial experience, as the design, regulatory approvals, and overall management is the responsibility of the principal investigator. The principal investigator oversees the site of the clinical trial to ensure the trial is being conducted in accordance with standard research regulations and protocol.¹

KEYWORDS EXPLAINED

Good Clinical Practice

Clinical trials are extremely meticulous, requiring detailed documentation and record keeping and precise adherence to protocol. Good clinical practice (GCP) is a set of international ethical standards designed to ensure the quality of clinical trial data and protect the well-being of clinical trial participants. The GCP standards outline specific rules for the way a clinical trial is designed, conducted, recorded, and reported. All members of a clinical trial team are required to be certified on GCP guidelines prior to becoming involved in a clinical trial.²

Clinical Site Agreement and Site Initiation Visit

For sponsor-initiated clinical trials, the sponsor will usually contact an investigator and share the protocol of the clinical trial with the intent of determining whether the investigator is interested in participating.

Once the investigator agrees, the sponsor will compose a clinical site agreement (CSA), which serves as a contract between the sponsor and investigator to detail the roles, responsibilities, and compensation for conducting the clinical trial. After the CSA has been negotiated and signed, the sponsor will visit the investigator’s clinical site to train the staff and verify that the site has the necessary equipment to properly conduct the trial.

Clinical Trial Regulatory Binder and Protocol

Each clinical site participating in a clinical trial will create a regulatory binder that stores all documents related to the clinical trial, including the protocol, clinical team credentials and certifications, the manual of procedures, and record of Institutional Review Board (IRB) approval. The IRB is an organization that ensures each clinical trial is conducted in accordance with regulatory standards and protects the rights and safety of clinical trial participants.

Once a sponsor or investigator has created all necessary documents for the clinical trial, the documents are then submitted to the IRB for review and possible modification prior to initiation of the clinical trial. During the execution of the clinical trial, any significant adverse events or errors that could potentially compromise the safety or privacy of a participant must be reported to the IRB for review.³

The clinical trial protocol, a detailed document created as a blueprint for the trial, should also be included in the binder. The protocol provides details of the objectives, design, procedures, endpoints, statistical considerations, etc, of the clinical trial.

Informed Consent Form

The informed consent form (ICF) is the most important participant-facing document. This form provides the potential participant with a detailed overview of the clinical trial, the procedures, the possible risks and benefits, their rights as a participant, and their compensation. Each participant must be given sufficient time to review the ICF and sign it prior to initiating any clinical trial-related activities.¹

Case Report Forms

All clinical trials have specific testing and order of testing defined by their respective protocols. Case report forms are where results of the tests conducted during a clinical trial visit should be recorded. They also serve as a guide to the investigator on conducting the appropriate testing during a clinical trial visit.

Contract Research Organizations

Contract research organizations (CROs) are companies that assist clinical trial sponsors in a wide range of activities, including protocol development, IRB document submission, and patient recruitment. However, data monitoring is the most prominent function of CROs, in which their clinical research associates (CRAs) visit research sites and review all clinical trial documents for accuracy and compliance with the protocol. CRAs can also verify data entered by the clinical trial investigators without needing to visit the site.

Electronic Data Capture

Most clinical trials use electronic data capture (EDC) to upload the data recorded during clinical trial visits. This allows the sponsor and/or CRAs to monitor the progress of the clinical trial remotely. Any errors found in the EDC are queried to the study team, so they have an opportunity to correct them.

Participant Recruitment and Enrollment

Participant recruitment can be conducted by a CRO or the clinical trial site itself. Once a participant has signed the ICF, as discussed previously, and agreed to participate in the clinical trial, a screening visit is conducted to determine whether the participant meets all the inclusion and exclusion criteria to qualify for enrollment.

Clinical Trial Completion and Data Analysis

After all participants have completed the clinical trial, the final data undergo meticulous monitoring for accuracy prior to data-locking and statistical analysis. The analyzed safety and efficacy data are then submitted to the FDA for approval to proceed with the next phase of the clinical trial or to bring the drug to market, in the case of phase 3 clinical trials.²

where to start

A great place to start looking for clinical trials that may be of interest to you is clinicaltrials.gov. This website allows you to see completed, active, and upcoming clinical trials. Once you have identified a clinical trial that you believe your site would be a good fit for, reach out to the company with the email provided on clinicaltrials.gov to begin the discussion about possible participation. (Part 2 of this series will go into more detail about the preliminary discussions between a sponsor and a potential investigator.)

The following are considerations for determining whether your site would be a good fit for a specific clinical trial. Some of these areas will not be apparent until the sponsor has shared more details about the study.

Staffing

Does your site have the staffing and bandwidth to take on the extra workload (eg, recruitment, subject exams, and administrative tasks)?

Facility

Does your site have the necessary exam rooms, equipment, and storage space?

Patient Population

Does your site have a patient base that will allow you to meet the enrollment goals of the sponsor?

Regulatory Compliance

Does your site meet all the regulatory requirements for conducting a clinical trial, including GCP guidelines?

Ethical Considerations

Can your site uphold ethical standards and patient confidentiality throughout the clinical trial process?

Time Commitment

Can your site commit to the clinical trial’s timeline for enrollment, follow-up visits, and reporting requirements?

GET INVOLVED

Clinical research is a specialization that remains underutilized by most optometrists. Engaging in clinical trials can be a rewarding endeavor that can positively affect patient outcomes and pave the way for future breakthroughs. Next up: We will discuss the nitty gritty details of each phase of a clinical trial, including understanding methodology and interpreting outcomes.