A Quick Guide to Getting Your Device into Clinical Trails [For Researchers]

After years of development, hundreds of liters of coffee, numerous late nights and copious master and PhD theses later, you finally have a medical device that is ready to be tested on humans. You know it’s safe, you even have a fully working device that you are planning to use. All you need to do now is to fill out the relevant application documents for a clinical trial…right? 

It’s easy to think that the final step of applying for the clinical trial is ‘just a matter of a few documents’, especially when you consider how much money and effort was put in over the years to ensure the safety and effectiveness of the device. But now you are suddenly faced with the realization that you not only have to fill out some documents, but the order and method of filling out these documents was important. So, what to do now? Do you have to dismantle your device and start again? Do you have to re-do all your long and expensive experiments in a specific way? Do you have to hire some very expensive consultants to help you with this task?

Medical device regulations in many countries operate on very basic principle: devices that are to be used on humans (either through clinical trial use or on the open market) must be safe and effective. To ensure that the safety and effectiveness of the device can be really well understood, all aspects of the device need to be well understood. For example, it is no good to source some material from a supplier for a device to be implanted into a human if it is not well understood exactly what is in the material. This is why it is important to have some control over how the device is developed, manufactured, tested, delivered and used. This is where quality processes and a quality management system comes into play.

For researchers trying to go into clinical trials, the notion of a complete quality management system can be a bit daunting (and expensive and slow sounding!). However, implementing a complete quality management system based on a bunch of comprehensive documents written by regulatory bodies may not be the best approach. Very often, these documents need to be very comprehensive in order to cover a wide range of different kinds of devices and a range of different risk categories. Following these documents will probably just result in a quality system that is a much larger beast than is needed. Not only that, but you may convince yourself that you should dismantle the whole device and start from scratch which may not be needed.

To give you the best shot at success, we have compiled a few tips on how to prepare your device for a clinical trial.

Start from the Start

We don’t mean that you have to scrap your device and start again. Absolutely not! In fact, you may not even need to change or redo anything here. What we mean is, you should actually step through one ‘iteration’ of development using a controlled quality process. Use this step through process to complete all documentation as well as to double check everything. The purpose of a quality process is to ensure quality, so use the process to do just that. For example:

1. Determine all of the goals (a.k.a intended use,  user needs, quality, safety and performance requirements etc.)  that your device must meet in order for it to be acceptable.
2. Identify all of the risks (usage, misuse, manufacture, supplier, biocompatibility, cleaning, etc.)
3. Identity how you will address the risks (use hierarchy of control – Elimination, Substitution, Engineering controls, Administrative controls, Personal protective equipment) and how you will mitigate them
4. Collect all design documentation that you already have lying around (you don’t need to generate new design documentation, just collate what you already have), 
5. Continue stepping through the process until complete etc…

Only Do What is Needed

At the point of going into a clinical trial, it is possible that you only have a few devices lying around and these are the ones that are expected to be used on patients. It is also possible that the budget will not squeeze to making more. For mass production, it can be extremely important to conduct process validation, calibration and maintenance scheduling, employee training, and auditing. However, for researchers, it may be sufficient to show that the exact devices to be used in the clinical trial meet their required specifications. This means, if you forgot to calibrate something during manufacturing, you do not necessarily need to dismantle the device and make a new part, you might be able to simply re-calibrate and re-measure. Your best defense is a comprehensive inspection protocol that shows that all relevant goals (requirements) have been met. 

It is important to note, however, that everything must meet specifications and must be able to be documented as such. If you are unable to confirm something, it is not usually acceptable to skip it. For example, if you remember that the plastic you used was supposed to be biocompatible, but you can no longer find the material certificate for that batch, you cannot cite a phone call as evidence. You really should confirm this either by getting a new part manufactured with the correct documentation or getting a biocompatibility test conducted commensurate with the intended use.

For clinical trials with devices that are single use, or where a large number of exemplars are needed, it might be more efficient to validate the process of manufacturing them than thoroughly inspecting each device. A risk based approach to design of the manufacturing and inspection process should allow you to identify the best way for you. Don’t forget, outsourcing manufacturing to a competent supplier may also take a large burden off you and may even save you money in the long run, depending on your needs.

Use Sound Scientific Reasoning

If there is something that you have probably spent a lot of time on as a researcher it is testing. However, it is also likely that many of the scientific experiments and papers that you want to use as evidence of the device meeting the required safety and effectiveness may actually be based on various different versions of the device. It is not usually reasonable to simply point to these scientific papers as evidence of safety without also being able to confirm that the device you have now is the same as the device you used in those experiments. It is also not always scientifically sound to make the statement that because some aspect of the device has been ‘improved’ that this will ultimately result in ‘better’ results than the one reported in the paper.

However, just because the device is a little different, does not mean you have to throw away all the papers and start the experiments again. This is where scientific reasoning comes in. There are a few different ways that you can continue to use your old experiments as evidence for your current device, even if the devices differ. Here are a few examples:

• If the change to the device is purely technical and is very well understood, sound argumentation may be used. For example, a substitution for a larger battery is likely to result in longer use (however, if it is important how much longer, testing is probably required as a battery double the size may not always result in double the use time).
• A smaller confirmation test can be conducted that shows that the results of this device are equivalent to the results of the previous device. Choose a sample size that can make a statistically significant confirmation.
• Get experts in the field involved to write a report. For example, you may not need to re-test a well understood raw material for biocompatibility (such as certain grades of stainless steel), but you might need the input of a toxicologist to analyze whether certain manufacturing processes might lead to unacceptable changes.

Iron Out Problems Now!

Although it might be tempting, rushing your device to clinical trial even though one or two of the above are still a little hazy can be a big problem for you. If you need to make changes to your device because of an issue, apart from risking the patient’s safety, you run the risk of invalidating your results. Without statistically significant results, you are wasting everyone’s time and money.