Mobile technologies for clinical trials represent the future of the industry, said Jay Udani, MD, founder and CEO of Medicus Research.
The use of mobile technology for patient reminders, compliance, food records is on the rise, said John Marshall, VP of operations for Biofortis, and it’s an innovative trend to help tighten the control of the study.
Harnessing the technology is dependent on participants’ access to it, and Marshall notes that about 40% of Biofortis’ study participants own smart phones, with the number increasing rapidly.
“Our clinical trials management system has smart phone capabilities and we have just begun utilizing this type of technology,” he said.
Recruitment
Technology can also be leveraged to facilitate patient recruitment, and NDI uses a combination of old and new – social media, its historical database of previous patients, radio, newspaper and other e-tools – to meet recruitment needs, said William Rowe, president & CEO, Nutrasource Diagnostics Inc.
Jill Stocki, director of business development for Biofortis, added that it is also using the old and new approach to recruitment. “Social media is still in its infancy for patient recruitment but we expect this to grow as the popularity of Facebook, Twitter, and others expand to more age groups and ethnicities.”
So who is volunteering for these trials? In general, subjects have a high interest in nutrition clinical trials due to the thought that nutrition studies are, in their mind, a less risky option than drugs studies, she said.
“However, pharmaceutical clinical trials, in general, pay more for participating which makes them more attractive for those who are financially motivated,” said Stocki. “It is important to add that some nutrition/supplement studies do not provide a health benefit (e.g. bioavailability studies) so the subjects will need to be remunerated similar to pharmaceutical trials.
“Subjects who participate in nutrition clinical trials tend to be individuals with flexible work schedules or stay-at-home moms who have a high interest in nutrition. In general, these subjects lead a healthier lifestyle, with the exception of the ones that volunteer for more disease-risk studies, such as obesity studies.”
The ability to recruit subjects for studies involving natural products is surprisingly easier than recruiting individuals with specific diseases, said Alexander Schauss, PhD, senior research director, Natural and Medicinal Products Research, AIBMR Life Sciences, Inc. This is because there are (or should be) far fewer inclusion and exclusion criteria.
“People are interested in natural products that might be beneficial to their health. They also perceive such products as safer and less likely to cause an adverse reaction than pharmaceuticals,” he said.
‘Human guinea pig’
Dr Udani, however, takes an opposing view. “With regard to healthy studies vs. disease studies, recruiting for a dietary supplement study is more difficult that recruiting for a pharma study involving people with certain diseases,” he said. “In a pharmaceutical disease study, the people with that condition operate under what’s known as ‘the therapeutic misconception’. Meaning, they believe that by entering into a clinical trial they are going to benefit their condition – this is big part of their incentive for signing up. In reality, however, they may receive a placebo or the investigational drug may not benefit their condition.
“In a healthy volunteer study, you don’t have that incentive,” he said. “Those who join a study are doing it for one single reason – financial compensation. Therefore, the compensation needs to be large enough to interest the right group of individuals.
“The recruitment goal is not just to sign up enough people to join a study – it’s about getting the right people. By enrolling participants in a study who reflect a company’s customer demographic and sociographic profile, the company will be able to observe how their likely customers in the real world will react to their product.
“This is of greater value than if enrolment was simply based on meeting a quota of participants.”
Cost also comes into play when considering how many people to recruit in order to power a study enough to detect a treatment effect when compared to a placebo, said AIBMR’s Dr Schauss.
Subtle effects
“Therefore, the challenge is whether the sponsoring company has the budget to support the ideal study design,” said DeAnn Liska, PhD Senior Director, Nutrition and Scientific Affairs for Biofortis.
“It is certainly difficult to make healthy people healthier,” she said. “That said, many trials on dietary and nutrition supplements assess tolerance, bioavailability, or markers of healthy function such as regularity/laxation, cognition, and satiety that are conducted in participants meeting a generally healthy profile.”
Subtle effects also make compliance with a study protocol even more vital, said Dr Udani, and this led Medicus Research to develop its eCompliance suite of apps.
“When you have a dietary supplement that has a subtle effect to begin with, if a subject is not fully compliant with the study protocol, and if they don’t take the investigational product as directed, the possibility of the effect of that dietary supplement being seen during the clinical trial diminishes even further,” he said.
“With noncompliance, the relative effect of the placebo tends to be as large as the effect of the product itself. However, when you have near perfect compliance, the potential effect of the dietary supplement goes up, the relative placebo effect therefore goes down, and the likelihood of statically significant difference between the two is enhanced.
“But when a subject knows their compliance is being monitored, the likelihood of success is enhanced. Through these mobile technologies utilized in clinical trials, we are getting patient reported outcomes, scales, questionnaires, adverse event reports – all can happen through the mobile applications.”
Success
Clinical trials are an investment for any company, and ‘success’ often depends on the actual goals of the sporting company, and the goals must be understand at the time of clinical trial design. “Customers need to clearly understand their marketing, experimental or health claim objectives and how the clinical trial design must reflect these objectives should the data be positive,” said NDI’s Rowe. “Selecting the key end point or biomarker along with the correct study population is essential to optimizing a successful clinical trial. If a health claim or marketing claim is to be pursued, understanding the regulations and how the claim needs to be substantiated via the clinical trial is paramount.”
One of the greatest challenges for supplement developers is to design studies that will support claims in the long run, said AIBMR’s Dr Schauss. “Of course you can't make disease claims with supplements,” he said, “and there are future regulatory issues to consider with regard to performing "drug-like" or disease treatment trials on a dietary ingredient (e.g. the possibility of needing an IND, potential challenges if you later would like to gain GRAS or NDI status, etc.).”
Medicus utilizes the Udani Theory of Natural Health Product and Clinical Trial Design, which was developed to establish a way for clinical trials to meet a manufacturer’s substantiation goals, while also keeping an eye on ever-changing regulations. The three steps include identifying a healthy or at-risk population, applying a standardized stressor to overwhelm their physiology or standardize all secondary variables which could influence the endpoint, and selecting endpoints that are relevant, not only scientifically, but to the regulator and to the consumer.
Deadlines
If the design meets the end goal, and the study is powered sufficiently to be able to have a certain degree of confidence (e.g., 95%) that the study results reflect the impact of the product or ingredient and are not observed by chance, then the remaining metric in determining overall success is whether the CRO can finish the study on time, said Jill Stocki.
“Clinical trials take time and there are many factors that can influence timeline,” she said. “Sometimes sponsors and CROs underestimate the actual amount of time to recruit, enroll, analyze, and report the study results.
“It is important for the CRO to accurately estimate the time to complete the trial so expectations are clearly outlined. This is where working with an experienced CRO/clinical site has its advantage. Evaluating the CRO on their experience with timelines is a critical piece of information to consider when looking at outsourcing.”