Remote Decentralized Clinical Trials Could Solve RCT Problems

Europe’s Innovative Medicines Initiative has launched a new project, Trials@Home, to evaluate how remote decentralized clinical trials (RDCTs), which use new technologies to allow bigger, more diverse and remote populations to take part in clinical trials, could become the gold standard for clinical research. The project’s coordinator, Diederick Grobbee, explained to the Pink Sheet how RDCTs may replace traditional randomized control trials (RCTs).

The launch of the project came just before Janssen announced on 16 November its own decentralized trial to evaluate the effectiveness of Invokana (canagliflozin) in adults with heart failure, with or without type 2 diabetes. Janssen, which is also part of the Trials@Home project, says that all contact with participants in its trial will be done virtually, with no in-person clinical visits required.

According to Grobbee, “classical RCTs are, in certain therapeutic areas, almost impossible to sustain because of the size and cost of studies.” The growing demand for real world evidence and the emergence of big data analytics and new digital technologies is also driving demand for new paradigms, he said. Grobbee is also chief scientific officer at the Julius Clinical Academic Research Organization in the Netherlands.

The Trials@Home project is funded by the IMI, a joint enterprise between the European pharmaceutical industry body EFPIA and the EU’s Horizon 2020 R&D innovation program. It is being run by a consortium of 31 members led by Sanofi and the University Medical Center Utrecht. The project will eventually conduct a pilot comparing an RDCT alongside an RCT and a hybrid model with the aim of establishing a set of guidelines that companies could use to conduct their own research.

The project will run for five years with a budget of €40m ($44.3m). Over that period, Groebbe hopes it will make big strides in using new innovative technologies such as apps and wearable devices to enable trials to be conducted remotely, and “bring them to patients rather than bring patients to the trials.” The consortium hopes that moving the trials from the traditional clinical setting, RDCTs will be faster and more efficient through the gathering of real world evidence.
New technologies include applications that monitor compliance, including smart phones. Grobbee also pointed to sensors that can measure certain things like glucose, blood pressure, heart rate and weight. And given the increasing interest in patient reported outcomes, these could also include technologies to allow patents to input data themselves, he said.

According to Grobbee, the model also allows for the collection of data from different sources, rather than relying on case report forms. For example, a combination of patient reported outcomes and data extracted from routine clinical data could be gathered, he said.

There is no limit on the type of medicines for which the RDCT approach could work, said Grobbee. In chronic conditions, trials are generally very laborious and large, with up to 20,000 patients. “That requires massive resources and is extremely costly. They are difficult to sustain, and more cost-effective solutions need to be found,” he said. Meanwhile, it can be difficult to include rare disease patients in a trial if they live remotely and in different countries.

A Lot Of Interest

There have been few attempts at a wholly RDCT approach, according to Grobbee. Instead, he says many trials use “bits and pieces” of the concept but in a traditional setting. As such, the first phase of the project will explore an inventory of studies that are already conducted using new technologies to better understand how they are used and the possibilities that they lay open. In addition, studies will be evaluated in terms of methodology and the regulations and ethical requirements associated with them.

Then, within two and a half years, the project will initiate a pilot comparing a wholly RDCT model with a traditional RCT and a hybrid approach. The pilot will look at the impact of the type of study on the efficiency of trials, the quality of data and also how patients and physicians engaged in the studies.
The pilot should result in a set of recommendations that companies can use to conduct their own trials, said Grobbee.

He thinks the pilot will last around six months and that the pharmaceutical used will be for a chronic condition, though this is yet to be confirmed. The project has had a lot of interest and a number of companies participating in the consortium have put their products forward for the pilot, he said. “We might have too much to choose from.”

The consortium also includes representatives from regulators, primarily the European Medicines Agency, and payers and health technology appraisal bodies. As such there will be ongoing discussion about how trials will meet needs of payers and regulators, which will be reflected in the final guidelines.

Janssen’s Decentralized Trial

Meanwhile, Johnson & Johnson company Janssen last week said it had launched the “first ever ccompletely decentralized, mobile, indication-seeking study.”
According to Grobbee, the trial should provide useful information about RDCTs “alongside the thorough analyses made in Trials@Home.” However, he added that it is not “an exhaustive inventory or scientific assessment of the methodology which is the aim of Trials@Home.”

Janssen’s study, called CHIEF-HF, will assess the effectiveness of Invokana in adults with heart failure, with or without type 2 diabetes. It will compare Invokana against placebo on quality of life improvement scales, in participants with either preserved or reduced ejection fraction heart failure. It will support clinical data from the Phase III program that supports Invokana.

The study will take place in the US and will enrol around 1,900 participants. All contact with trial participants will take place virtually and no in-person clinical visits will be necessary, said the company. This should “accelerate the study and fast-track the results,” it said. Smart devices and wearable devices will more quickly and efficiently gather and analyze real world data.

“Investigators will analyze participant-reported outcomes through app-based clinical questionnaires, and physical activity data as logged by an app on the smartphone and actigraphy data from a wearable activity device, including daily step count and stairs climbed,” Janssen said.

“Traditional clinical trials are undeniably essential in medical research but are often long and costly. Through the CHIEF-HF study, we are exploring how we can harness technology that consumers already have at their fingertips, including smartphones and wearable devices, to change this paradigm,” said Paul Stoffels, vice chairman of the executive committee and chief scientific officer at J&J.