Michelle Petersen, founder of Healthinnovations, takes a deep dive into the importance of implementing virtual clinical trials, the challenges still facing them and how the development of Electronic Health Records, synthetic biology and nanopores could overcome these in the next 10 years.
It is known that the ultimate goal of virtual trials is to reach and engage patients in the most personalised of ways, however, in multi-site trials, less than 5% of patients are currently participating in clinical research, with 49% of participants dropping out before their study ends, suggesting that one-size most certainly does not fit all when it comes to these trials.
The financial aspect is also a major factor with the average price tag of developing and bringing a novel pharmaceutical agent to market coming in at around $2.6 billion over approximately 10-12 years; conversely the cost of managing a single study site is deemed to be between $1,500 and $2,500 per month, offering considerable savings, and a reduction in prerequisite local regulatory requirements which are currently unstandardised. This is also married with the high, and often aggressive competition for clinical trial sites meaning a lot of innovation is lost where new or niche biotech simply don’t have the contacts or money to outbid more established blue-chip entities.
It’s important to step back here, as we also don’t want unregulated remote trials being held out of a cheap motel room or in a mobile home to avoid detection either. This is why it so important for local medical teams to be part of the trial, as well as the development of a searchable database of remote clinical trial investigators who must register, and be legislated even more heavily than is currently done. Once again, standardisation and stream-lining of local, state and national regulations will be crucial in this endeavour, to ensure these unqualified CROs aren’t lost in a mountain of regulatory loop-holes and triplicate filings, or under multiple different names and descriptions for the same regulation or code.
Everything is pointing towards siteless virtual trials via mobile phone, portable wearables and cloud-based technology, and as this technology is already in use it would suggest we will reach full virtual clinical trials in the next 10 years quite effortlessly. However, logic would dictate that there appears to be many obstacles currently in the way, with quality of data the single biggest hurdle for both multi-site and remote clinical trials today. Even though the gathering of data encompasses many different facets, such as inspection, technologies, regulations and Electronic Health Records (EHRs) to name a few, data comes from one source, namely the patient. It therefore makes sense to concentrate on this source, the participant.
Patient-centric virtual trials
There is no doubt that remote trials represent a more patient-centred approach, maximizing patient eligibility and enrolment in the study. As well as some day seamlessly collecting safety and efficacy data from human trial participants in their own home, virtual trials will allow those with mobility issues, such as the elderly, or patients who live in rural areas to participate in the trial within their comfort zone, reaching normally unobtainable subjects.
Maximising sign-up and retention, the all-important comfort zone, means there must be a much larger role played by the patient’s local health team, who understand the patient’s condition on an individual basis, producing personalised medicine due to environmental factors. EConsent and virtual programs explaining how to access apps and EHRs will also add to the comfort zone for the remote patient. As the old and infirm can take part, quality of data will be greatly improved, leading to a far more realistic demographic for some drugs, and more randomized trials, producing more realistic results. This will all hinge on Electronic Health Records.
The power of Electronic Health Records
Thus, remote clinical trial investigators must invest in sophisticated technology in order to maintain data collected electronically. Currently, most pharmaceutical companies and contract research organizations (CROs) lack the systems needed to efficiently deal with the large amounts of data collected, plus a unified clinical environment is also needed involving a harmonizing of trial information and consent regulations. Currently, different data models and vocabularies exist for the same trial documents, content, and information, it's imperative that the same nomenclature for these is used throughout the trial and EHR, ensuring documentation is transferable between different types of raw data sets, U.S state systems, and makes of EHR. In short, EHRs are key to tying the patient, local health team and remote site together.
Immediate relay of patient status data in real time is highly desirable for successful clinical trials, which will enable medical teams to act quickly in an emergency and will shorten the length of studies. Patients must be able to access and check their own EHR via mobile phone health apps or on their home computer if preferred; this system should also have sound independent channels for complaints and reports of adverse events.
In the next 10 years Artificial-Intelligence (AI) will greatly improve these EHR systems, working beside clinical investigators, highlighting human error such as misdiagnosis and missed pathology. Doctors are already starting to compete (and lose) against deep-learning systems in disease diagnostics and various spectroscopy. In theory AI should also be able to sweep for incorrect data entries and software glitches in EHR systems.
How synthetic biology is changing everything
In regards to realtime data collection of whole body systems, technology-wise, we’re about to step it up a gear - synthetic biology, or synbio, IS changing EVERYTHING, not just clinical trials. Synthetic biology involves the fabrication of previously non-existent biological components and systems, in some cases the biological component can assemble itself, with the artificial cell mimicking a naturally occurring biological cell. The construction of artificial cells focuses on building ‘minimal’ cells by reducing or simplifying the genetic network of a living cell, producing a theoretical cell with the minimum number of genes needed to survive and to fulfil the desired programmed function.
For instance researchers have engineered artificial cells which can sense, react and interact with bacteria, as well as function as systems that both detect and kill bacteria with little dependence on their environment. In theory artificial biological systems can be bioengineered to fulfil any desired function, including the type of entities being trialled and the monitoring of the whole human system in real-time. In fact these systems will be so single-cell sensitive, potentially they could be used to monitor the effect and offset of a biological drug or NCE on every genetic system in the body, and the information provided plugged into AI-based algorithms in future in silico drug design systems.
Great strides are currently being made towards this end with much research concentrated on the synthetic microbiome that can record information about the state of the gut in real-time, and report the presence of disease or suspicious activity. Currently, researchers have engineered a genetic signal-transmission system in which a molecular signal sent by bacteria in response to an environmental cue can be received and recorded by a different species of bacteria, namely E. coli, in the gut of a mouse. In theory this may work for artificial bacteria which can also interact with the environment to report on any adverse events and correct them. For the future, the researchers are working towards a synthetic microbiome with engineered bacteria species in the human gut, each of which has a specialized function, such as detecting and curing disease, creating beneficial molecules, improving digestion, and communication between engineered bacterial species to ensure that they are all balanced for optimal human health.
However, until we reach optimal status for the synthetic microbiome and other synbio, nanopores will be the next gen wearable used in trials in the next 10 years. Nanopores produce an ionic current and can accurately measure specific molecules in a nanolitre of human fluid continuously with no sample preparation. Whilst they do not currently possess the scope or sensitivity of synbio, it is predicted that incorporation of nanopore-based technology into portable electronic devices will allow the development of sensitive, continuous, and non-invasive sensors for metabolites in point-of-care and home diagnostics. With researchers planning to develop a nanopore system with proteins which are specific to hundreds of different metabolites, these next gen wearables will be easily connected to the patient’s electronic-based comfort zone via lab tags providing them with a wealth of health data and information.
Thus, we come full circle, with next gen technology being used to interest the patient, to engage the patient, to allow the patient to take more control over their health in clinical trials, whilst cutting costs and vastly improving the quality of data in remote clinical trials. All that is left to be assured now are the legislative and regulatory aspects, which unfortunately may not be as simple as it seems, and which greatly needs the input of both pharmaceutical and academic entities in governmental regulatory design briefings.
ABOUT THE AUTHOR: Michelle Petersen is the founder of Healthinnovations and the Health Innovator community. She has worked in the health and science industry for over 21 years which includes time within the NHS and Oxford University. An avid campaigner in the fight against child sex abuse and trafficking, Michelle is a passionate humanist striving for a better quality of life for all humans by helping to provide traction for new technologies and techniques within the health sector. You can follow her on Twitter at @shelleypetersen.