The use of mobile technology and wearables in clinical studies
The development costs of new pharmaceuticals have increased many times over the last decades. More than 50 percent of all expenditures are now channeled into clinical development. Using mobile technology and wearables to make clinical research safer and improve financial viability could bring about a fundamental change in clinical research in the years to come. The Steinbeis Research Center ProMyelo has now entered into a project alliance to investigate how this could work in practice.
Clinical studies involve carrying out an experiment with the support of healthy test persons and voluntary patients. The idea is to examine important questions regarding new treatment options, vaccines, or diagnostic procedures, and even look into new application areas for known pharmaceuticals. Clinical studies tend to span several phases, taking place one after the other to identify any potential risks posed by a new treatment, the effectiveness of a medicine, or any impact that treatment may have on certain factors dictating quality of life. The aim of a Phase I trial is to determine any issues relating to the safety or tolerability of a pharmaceutical product in the body after administration. Human test persons are observed to ascertain the severity of any side effects after they have taken the medicine. In many cases, a Phase I trial only involves a small number of participants; perhaps between 6 and 10 healthy subjects will be enrolled. If the preparation being tested passes the first phase of a trial and is found to be tolerable, Phase II begins. The idea of a Phase II trial is to gather initial information on the safety and effectiveness of a potential new medicine among patients. It is also examined whether different dosages have an influence on the effects of a medicine. In many cases, several Phase II trials are carried out to check medicines among different patient groups or investigate indications. The actual proof of effectiveness and tolerability for a medicine comes from a Phase III trial. The aim of this trial is to replicate actual conditions as closely as possible. Phase II and Phase III clinical trials always include (at least) one control group. The effectiveness of the preparation being investigated is compared to that of a standard medicine (typically already in use to treat the condition). Alternatively, if there is no standard medicine, comparisons are made to a placebo. Phase IV studies are conducted after a pharmaceutical product has received regulatory approval from the competent authorities. This phase of a study (commonly referred to as post-marketing surveillance, or PMS) is designed to assess the long-term effect of treatment with a medicine. This approach makes it possible to understand more uncommon undesirable side effects. Overall, each stage of pharmaceutical testing is therefore designed to examine the effectiveness and safety of a potential new medicine.
Ideally, human test persons or patients will be monitored continuously at every stage of a study in order to establish as early as possible if there are any changes in a medical condition or side effects. But in reality, continuously monitoring people is (still) not practicable, unless of course people are tested in the rooms of the hospital or study center. This is why clinical studies tend to establish the effectiveness and safety of drugs by ensuring that the intervals between tests are more or less kept as short as possible. Depending on the condition being examined, people involved in the trial typically visit a physician every four to eight weeks in order to check the progress of their condition and see if there are any side effects. Doctors only have a limited amount of time to record test parameters. Long examination intervals and short windows within which to carry out the examinations entail two possible risks. The first is that possible side effects may not be detected until it’s too late or may not be noticed at all. The second is that the effectiveness of a new active substance may not be understood in enough detail. Both issues – by themselves or together – can result in delays in the approval process of a new drug, and this raises the cost of the individual trial phases. The Steinbeis Research Center ProMyelo, has joined forces with LMU Munich, RWTH Aachen University (C. Kohlschein; IMA and Dr. S. Jonas/mhealth), and Hannover Medical School (Prof. M. Stangel and S. Gingele) to examine the extent to which wearables can be used to recognize the side effects of drugs as early as possible and provide a more precise assessment of their effectiveness.
Wearables are basically all kinds of devices that are worn on the body and have been fitted with sensors. Signals from the sensors are transmitted wirelessly to share data with an end device, typically a smartphone. Examples of wearables are activity trackers worn on the wrist, smartwatches, measurement devices wrapped around the chest, electronic scales, blood pressure measurement devices, and clips attached to clothing. Apps are used to gather data from a wearable, and this is then forwarded via the internet to a trial center or the clinical investigator for systematic evaluation. Using wearables already makes it possible to monitor a whole host of bodily functions and factors such as skin temperature, weight, blood pressure, heart rate, quality of sleep, oxygen supply to the blood, or paces walked – so in essence, they facilitate realtime monitoring. They also make it possible to capture a variety of cognitive parameters such as speech recognition, memory, alertness, or cognitive controls and with the right apps, these parameters can be observed as a trial progresses.
The first step the Steinbeis experts intend to undertake for the WeSeni- MuS (Wearable Sensors in Multiple Sclerosis) project will be to investigate whether wearables can be used to monitor the state of health of people with multiple sclerosis (MS). To do this, volunteers and MS patients will be given different types of sensors to wear. Their health will then be observed according to established clinical procedures, and this will be compared to the measurements taken by the wearable sensors. Aside from tracking their mobility (using the Apple Watch Series 3 and a Garmin vívosmart HR+ fitness tracker), daily measurements will be taken of their blood pressure (QardioArm), weight (QardioBase), cardiac activity (QardioCore, a wearable ECG), and oxygen saturation (iHealth Air Pulsoximeter).
Motor impairments are known among MS patients, but it is less common to observe MS patients already suffering from cognitive deficits during early stages of the condition. Yet up to 70 percent of patients are affected by this. Cognitive problems become noticeable when patients have difficulties concentrating or paying attention, or become increasingly forgetful. The experts have proposed using two specific groups (batteries) of neuropsychological trials: a Brief Repeatable Battery for Neuropsychological Evaluation (BRB-N) and a battery called Minimal Assessment of Cognitive Function in MS (MACFIMS). These will help assess the cognitive performance of MS patients. Both batteries span several tests at the same time. The MACFIMS can be completed in around 90 minutes; the BRB-N takes roughly 35 minutes. The aim of this kind of neuropsychological testing is to evaluate different types of cognitive performance traits, such as attentiveness, memory, language, flexible thinking, and problem-solving abilities. Regular cognitive testing among MS patients is not widely established practice in clinical settings and rarely features in clinical trials. The researchers have entered into a partnership with the makers of an app called Peak to adapt smartphone software so as to capture not just physical data but also patient performance in a variety of cognitive areas. The aim of the Steinbeis experts is to use the subproject to answer some fascinating questions, such as whether using the app to measure the cognitive abilities of MS patients will provide reliable information compared to established testing procedures.
More and more clinical trials now involve digital technology. According to a report issued by the Gartner Group in 2015, it was forecasted that around ten percent of clinical studies would involve the use of wearables by the end of 2017. As digital transformation accelerates, society is undergoing fundamental change and medicine will inevitably have to come to terms with this. In some fields, digital transformation has already reached an advanced stage, but in clinical research it is only just getting out of the starting blocks. Using smartphones or wearables on (and even in) the body could improve the reliability of trial data generated by MS studies. The Steinbeis Research Center ProMyelo would like to capture simultaneous information on physical and cognitive parameters and provide a holistic picture of patients – and thus make clinical studies more efficient, less expensive, and more importantly: safer.
Professor Dr. med. habil. Dr. rer. nat. Markus Kipp is director of the Steinbeis Research Center ProMyelo at the University of Munich. The Steinbeis Enterprise offers its customers support with the planning and implementation of research projects revolving around neurodegenerative issues, neuroinflammatory issues, or both. It also develops new in vivo animal models in the field of neurobiology as part of preclinical study projects (neuroscience).