A Guide to Successful Clinical Trial Design
Prior to the COVID-19 pandemic, the majority of clinical operations, studies and development were conducted in person. COVID changed everything, forcing and industry-wide paradigm shift in how clinical trials are designed and conducted. As we acclimate to a new normal, experts rightly wonder how the changes in communication strategies, tactics and tools will impact clinical operations and trial design in the years to come.
With a shift to more virtual clinical trials, what lessons can we apply to clinical study design? And what novel technologies can bolster their efficiency and clarity of their results? This guide covers what you need to know about successful clinical trial design in the post-COVID world.
01: What is clinical trial design?
Whenever developing a new drug, therapy, procedure, or medical intervention, it must undergo rigorous testing before its release. These medical studies, also known as clinical trials, seek to confirm that the study subject of the trials is safe and does what it claims to do.
But knowing whether the objective of the trial is an effective intervention poses a significant challenge.
It’s much easier to determine correlation than causation. As a result, for a clinical trial to be meaningful, there needs to be a union between observational studies and experimental studies. You must ensure that any treatment effect is isolated by controlling for potential biases, confounding factors, and by minimizing possible variants.
Put simply, clinical study design can make or break a study. It must be designed properly to mitigate or eliminate such factors from confusing the results, or leading to improper conclusions.
02: Why is clinical trial design important?
The process of developing a new drug is complicated, to say the least. It can take years and millions of dollars for a drug to go from the lab to the pharmacy. In fact, only five in every 5,000 drugs that enter preclinical testing will ever progress to human testing. And of these, only one will ever actually make it to market.
A properly designed clinical trial can provide strong evidence supporting cause-effect relationships and form the basis for clinical and public health policy. But a poorly designed trial can bury a promising therapy before it ever has a chance to develop. The vast majority of errors in clinical trials are the result of poor planning and design. As one 2019 study notes:
“Clinical trial design is an important aspect of interventional trials that serves to optimize, ergonomize, and economize the clinical trial conduct…A well-conducted study with a good design based on a robust hypothesis evolved from clinical practice goes a long way in facilitating the implementation of the best tenets of evidence-based practice.”
Generally speaking, there are several types of clinical studies and designs, including:
Meta-analysis
Systemic review
Controlled randomized trial
Cohort study
Case-control study
Cross-sectional study
Case reports and series
Animal research studies
03: What are the key features of clinical trials?
There are many fundamental factors that researchers must weigh as they design a clinical trial, including:
Clearly defining the research question – Every clinical trial design begins with the fundamental clinical research question. Over time, the team must refine it from a vague concept to a testable and quantifiable hypothesis. Only after the question is well understood can a research team begin identifying the intrinsic challenges of the study.
Minimizing variation – The greater variation throughout the trial, the harder it will be to narrow down any treatment effect. Ways to reduce variation include: constructing consistent and uniform endpoints definitions, using central labs for quantifying laboratory parameters and using standardized parameters in how study participants.
Promoting randomization and stratification – The more randomization that’s introduced into a trial design, the less chance there is for bias to creep in. And a stratified randomized trial helps ensure that treatment groups or study subjects are balanced regarding potential confounding variables.
Blinding – As one of the most fundamental design elements of any clinical trial, blinding ensures that a study’s participants and researchers are unaware of the assigned intervention, which prevents biases or behavioral changes from muddying the results.
Placebos – Similarly, placebos or sham interventions, help ensure that blinding is maintained, though such design features are typically limited to pharmaceutical interventions and not medical devices.
Selection of the control group – A control group gives researchers important data of what would have occurred had the study’s participants either not been treated or been given a different intervention. There are three types of control groups: historical controls, placebo controls and active controls.
Selection of a population – Researchers have to consider the intended target use for the intervention. A study on a drug that helps men aged 65+ manage their heart pressure would be moot if the tested population consisted of young adult women.
Selection of endpoints – An endpoint is intended to address the main objective of the trial. That means it needs to be, “clinically relevant, interpretable, sensitive to the effects of intervention, practical and affordable to measure, and ideally can be measured in an unbiased manner.” Typically, endpoints fall into one of three categories: continuous, categorical and event-time.
Sample size – Statistically speaking, it’s impossible to draw conclusive results from a sample size that’s too small. Similarly, a sample that’s too large will be difficult to control and costly to conduct. As a result, researchers must calculate a happy medium based on the planned analyses.
04: Types of clinical trials
While there are several types of clinical trial designs and clinical studies, it’s helpful to break them down into three broad categories:
- Pharmaceutical clinical trials
- Disease specific clinical trials, oncology for example
- Medical device clinical trials
Pharmaceutical clinical trials – Every prescription drug on the market must be approved by various regulatory authorities, such as the USFDA. For that, it must undergo rigorous pharmaceutical clinical trials that include a 10-step approval process:
- Preclinical (in vivo) testing
- Investigational new drug application (NDA)
- Phase I clinical trials
- Phase II clinical trials
- Phase III clinical trials
- Regulatory review meeting
- NDA application
- Application Review
- Drug labeling
- Facility inspection
Disease specific clinical trials – oncology for example. Cancer-related clinical trials are intended to test new ways to:
- Treat cancer
- Improve clinical oncology
- Find and diagnose cancer
- Prevent cancer
- Manage symptoms of cancer and side effects of treatment
For these types of studies, the clinical study is often the last step in a multi-year process that began years earlier with lab research. But that’s not always the case. For instance, in 2020, the National Cancer Institute conducted an observational cohort study to help researchers determine how COVID impacted the outcomes of patients undergoing cancer treatment and how having cancer affects COVID.
According to an article published in the Journal of Child Neurology: “The randomized controlled trial is often considered the gold standard for establishing efficacy in a research setting. This design minimizes selection bias and distributes confounders, known and unknown, between study groups.”
Medical device clinical trials – Medical devices go through a different approval process than a drug study. Typically, it starts with a small pilot study, followed by a larger pivotal trial. If successful, the manufacturer can then submit the device for FDA approval. From there, manufacturers often choose to also conduct post-marketing trials.
A recent medical device trial was conducted on an epinephrine auto-injector for patients with Anaphylaxis. This randomized, cross-over, unicentric trial was intended to evaluate the following:
- Primary outcome measures Patient satisfaction after three months of use through a questionnaire
- Secondary outcome measures Adverse events related to the medical device and patient adherence to the medical device.
05: How to design a clinical trial
Wondering how to design a clinical trial that is effective and actionable?
06: The biggest challenges in clinical trials & how to avoid them
Designing a clinical trial that is effective throughout all phases can be a herculean task, but it’s critical if you wish to bring your drug, therapeutic, or medical device to market. While there are several factors that add to the difficulty, some of the most significant challenges include:
- Complexity of trials
- Time constraints
- Financial demands
- Lack of communication
- Slow recruitment
- Poor retention
- Increasing complexity of regulations and compliance standards
- Data collection, security, and disemmenation issues
The COVID-19 pandemic has not only re-emphasized the importance of well-designed randomized clinical trials but also highlighted the need for large-scale clinical trials structured according to a master protocol in a coordinated and collaborative manner. – The Lancet
07: Using technology to improve clinical trial design
Here is yet another place where, increasingly, technology is filling the gap – especially in response to COVID restrictions and limitations.
For instance, shifting a virtual advisory board or other type of interaction to a virtual engagement platform like Within3, allows for seamless communication, coordination, and collaboration, which helps sites, patients, and payers optimize a study’s design and then execute that vision. It allows for on-demand training, makes it possible to design trial protocols and materials then receive instant feedback, and keeps all critical stakeholders engaged.
By using the platform, you can streamline the entire clinical trial design process. This results in improved trial execution, smarter decisions, and fewer logistical headaches.
Want to see how modern engagement technology can improve your clinical trial designs? Read our case study to learn more.
Sources
- Medicine Net. Drug Approvals – From Invention to Market … A 12- Year Trip.
- NCBI. Clinical Trial Designs. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6434767/
- NCBI. Fundamentals of Clinical Trial Design. https://www.fda.gov/media/82381/download
- FDA. Drug Approval Process. https://www.fda.gov/media/82381/download
- New England Journal of Medicine. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. https://www.nejm.org/doi/full/10.1056/nejmoa2034577
- NIH. What are Clinical Trials? https://www.cancer.gov/about-cancer/treatment/clinical-trials/what-are-trials
- NCI. Clinical Trials, NCI COVID-19 in Cancer Patients, NCCAPS Study. https://clinicaltrials.gov/ct2/show/NCT04387656
- NCBI. Clinical Trials in Rare Disease: Challenges and Opportunities. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3964003/
- NIH. Clinical Tirals.Gov. Satisfaction of Patient With Anaphylaxis in the Use of a Medical Device. https://clinicaltrials.gov/ct2/show/NCT02854969?term=medical+device&draw=2&rank=5
- The Lancet. How COVID-19 Has Fundamentally Changed Clinical Research. https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(20)30542-8/fulltext
