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Keep it Simple: The Top 5 Steps for Successful Protocol Design

April 13th, 2021 | Clinical Trials | Article

Starting clinical trials in the right direction begins with a well-designed study protocol – the more comprehensive, the better. A well-designed protocol must focus on the objectives of the study, ranging from scientific methodology to patient safety parameters. However, successful protocol designs are also defined by how well they embrace simplicity and practicality as part of their criteria.

Recently, the Biorasi team had the chance to connect with Dr. Robert Wilkins, former PI and Founder of QPS Consulting, to discuss some of the more “common sense” best practices to consider during the protocol design process.

“Protocol design is where critical clinical trials derail,” notes Dr. Wilkins. “Be sure to keep your protocols simple for all parties involved in your study.”

Step 1: Build Endpoints to Regulatory Standards

Photo of Dr. Robert Wilkins

Dr. Robert Wilkins, Founder, QPS Consulting

“It’s important to use established outcome measures,” says Dr. Wilkins. “The FDA and other regulatory agencies have developed well-established scales for clinical trial outcomes. This can pose a problem if you believe that different measures might result in better trial efficacy.”

Finding the right balance between established regulatory guidelines and your study goals is key. Prior to confirming clinical trial endpoints, look to regulatory agencies for guidance on consistent outcome measures and work with them to integrate any steps that are critical to the study.

Additionally, with the focus on receiving regulatory approval for clinical endpoints, it is important to make your findings translatable to other parties, especially when data is being collected and standardized. Dr. Wilkins recommends keeping it simple, minimizing the extra science and cutting out superfluous material.

“Ask yourself, what are the questions that are going to drive the FDA to approve your product or move it to the next stage of development? You need to know the answer to these questions before you move to protocol design and establish the main point of your trial with the minimum number of questions or data points.”

Step 2: Keep Testing Simple

The same guidelines for practicality and simplicity in developing outcome measures also apply to patient testing during the trial. Inessential testing leads to unnecessary management of those extra data points, which, in turn, can lead to a loss of statistical power when analyzing data.

“In the first few weeks of a trial, stakeholders are focusing on site activation, patient engagement, and safety, which is imperative” says Dr. Wilkins. “But after that, it is the data that becomes the most vital commodity. Extra testing creates extraneous information that must be collected and analyzed. Without proper resources to review the data, trials can fall behind. Data can get old very quickly, and it can be very difficult to catch up.”

With extra testing leading to extra data points, the addition of extra time and extra costs may follow as well. Simplicity should always be considered while writing the protocols, reviewing all testing to ensure that it is necessary to the clinical trial goals and end results.

Step 3: Work Well with Others

Clinical trial protocols do not exist in a vacuum. They must be developed with the end goal of study execution and that goal must be understood by all parties involved. This is especially true of site staff.

“Don’t annoy the nurses,” jokes Dr. Wilkins. “All kidding aside, the nurses and other site or hospital staff that are running your clinical trials can make or break the study. Clinical staff keep the clinical trial moving – from patient screening to data collection – and they are your connection to patient engagement. This can include caregivers in the home setting as well. Making sure that individuals in direct contact with patient subjects are informed and comfortable with your clinical trial protocols optimizes efficiency and the overall sentiment toward the study itself.”

The myriad of stakeholders across a given clinical trial includes more than site staff. Patients and their families or caregivers, sponsors and CROs, and even institutional review boards (IRBs) will each be interacting with the protocol in one form or another. It is important to think about writing clear and concise protocol content for each group involved, like speaking to a wide audience, to avoid any potential obstacles when the trial starts.

Step 4: Collect Patient Input First

“The patient is irreplaceable in clinical trials, especially in rare disease trials where the number of available patients is limited and recruitment can be challenging,” notes Dr. Wilkins. “Building a protocol that takes patient centricity into account can improve screening and enrollment.”

Consider the following when integrating patient input into your protocols:

  • Involve your patients early in the protocol design process. Understand their needs and establish goal attainment for relevant endpoints and quality of life that matter the most to them.
  • Take into account their limitations, especially as they relate to current medical conditions, testing parameters, and travel burdens.
  • Provide education and training for patients and their families and caregivers. The importance of having everyone on the “same page” during the trial can prevent obstacles to engagement and trial drop-outs.

Step 5: Foster Understanding from the Beginning

Dr. Wilkins notes that it is standard practice to create patient consent forms at an accessible reading level, so as to ensure patient comprehension and understanding. “Why don’t we do that for clinical trial protocols?” he says.

“It is important that everyone interacting with trial protocols – from site staff to CRO teams – understand them. Protocols need to written at an agreed upon reading level to prevent confusion or errors that can affect patient safety and even trial milestones. For example, flowery language in trial protocols can be excessive and distracting. Content that strays beyond basic comprehension adds confusion.”

Simple Protocols Keep Trials on Track

While often addressing complex therapeutic areas, clinical studies – ranging from traditional methodology to decentralized and virtual solutions – thrive on efficiency and practicality. It is important to keep it simple from the very beginning.

“Anything confusing or superfluous that can trip a stakeholder up and make it more complex is damaging your protocol from the start,” Dr. Wilkins remarks. “A simple, straightforward approach needs to be your template when designing clinical protocols.”