Introduction

Better designs, site-less trials, all-digital data collection and PCM (patient compliance monitoring) can all save time and money in connected medical device clinical trials.  This article will help you choose which strategies will be a good fit to help you validate your connected medical device and its intended use for submission to FDA.

What is the baseline cost? (hint don’t look at the costs of drug studies)

If you want to save, you need to know the price tag. Note that the costs of drug trials, including CRO and regulatory affairs is an order of magnitude higher than for connected medical devices.  A JAMA report from Nov 2018, looked at drug trials and concluded that a mean cost of $19M was cheap compared to the total cost of drug development – $1-2BN.

Findings:  In this study of 59 new therapeutic agents approved by the FDA from 2015 to 2016, the median estimated direct cost of pivotal efficacy trials was $19 million, with half of the trial cost estimates ranging from $12 million to $33 million. At the extremes of the distribution were 100-fold cost differences, and patient enrollment varied from fewer than 15 patients to more than 8000 patients.

By comparison, the estimated cost of medical device clinical trials to support approval by the FDA, ranges from $1 million to $10 million. A report from May 2017 surveyed the costs of medical device clinical trials and the potential of patient registries to save time and money. The report has some interesting numbers:

1.The average cost to bring a low-to-moderate concern device from concept to 510(K) approval is $31 million. 77% of that is spent on FDA-related/regulatory-affairs activities.

2.The average cost for a high-risk PMA device averages $94 million, with $75 million spent on FDA-related/regulatory-affairs activities. Average of 4.5 years from first contact with FDA to device approval.

3.Clinical trials outside the US are 30% to 50% cheaper. Less than 50% of medical device trials are now conducted in the US.

I. Better study designs

Real-world data (RWD) and real-world evidence (RWE) are being used for post-market safety surveillance and for designing studies, but they are not replacements for conducting a randomized trial with a controlled clinical protocol.  FDA recently issued guidance for use of real-world evidence for regulatory decisions.  FDA uses RWD and RWE to monitor post-market safety and adverse events and to make regulatory decisions.

RWD and RWE can be used in 4 ways improve the design of medical device clinical trials when there is a predicate device that is already being used for treating patients.

1.Use RWD/RWE to improve quality and efficiency of device evaluation at study phases (feasibility, pivotal, and post-market), allowing for rapid iteration of devices at a lower cost.

2.Explore new indications for existing devices

3.Cost efficient method to compare a new device to standard of care.

4.Establish best practices for the use of a device in sub-populations or different sub-specialties.

You will need to factor in the cost of obtaining access to the data and cost of data science.

But real-world data may not be reliable or relevant to help design the study.  As FDA notes in their guidance for Using Real-world evidence to support regulatory decision making:

RWD collected using a randomized exposure assignment within a registry can provide a sufficient number of patients for powered subgroup analyses, which could be used to expand the device’s indications for use. However, not all RWD are collected and maintained in a way that provides sufficient reliability. As such, the use of RWE for specific regulatory purposes will be evaluated based on criteria that assess their overall relevance and reliability. If a sponsor is considering using RWE to satisfy a particular FDA regulatory requirement, the sponsor should contact FDA through the pre-submission process.

II. Site-less trial model

Certain kinds of studies for chronic diseases with simple treatment protocols can use the site-less trial model.  The term site-less is actually an oxymoron, since site-less or so-called virtual trials are conducted with a central coordinating site (or a CRO like Science37). Nurses and mobile apps are using to collect data from patients at home.   You still need a PI (principal investigator).

The considerable savings accrued by eliminating site costs, need to be balanced with the costs of technology, customer support, data security and salaries and travel expenses of nurses visiting patients at homes.

III. Mostly-digital data collection

For a connected medical device, mostly-digital data collection means 3 things:

1.Collect patient reported outcome data using a mobile app or text messaging

2.Collect data from the connected medical device using a REST API

3.Enable the CRC (clinical research coordinator) to collect data from patients (IE, ICF for example) using a Web or mobile interface (so-called eSource) and skip the still-traditional paper-transcription step. In drug studies, this is currently impossible because hospital source documents are paper or they are locked away in an enterprise EMR system. For connected medical device studies in pain, cannabis and chronic diseases, most of the source data can be collected by the CRC with direct patient interviews. Blood tests will still need to be transcribed from paper. Mostly-digital means mostly-fast. Data latency for the paper source should be 24 hours and data latency for the digital feeds should be zero.

There are a number of companies like Litmus Health moving into the space of digital data collection from mobile devices, ePRO and wearables. However, unlike validating a connected medical device for a well-defined intended use, Litmus Health is focused on clinical data science for health-related quality of life.

IV. PCM (patient compliance monitoring)

Once the data is in the system, you are almost there.  Fast (low-latency) data from patients, your connected device and the CRC (which may be nurses in a site-less trial) are 3 digital sources which can be correlated in order to create patient compliance metrics.  But that is a story for another essay.

Summary

We have seen that new business models and advanced technologies can help sponsors conduct connected medical device trials cheaper and faster. It may not be a good fit for your product.  Contact us and we will help you evaluate your options.

For more information read Gail Norman’s excellent article  Drugs, Devices, and the FDA: An overview of the approval process