Virtual Clinical Trials – “They’re here to stay”

I recently met up with Miguel Orri, Senior Director at Pfizer and manager responsible for the famous REMOTE virtual trial pilot. Despite all it’s challenges, there has been many positive outcomes.  Learning opportunities are what pilots are all about; figuring out what works and where to improve.

In one of the sessions at the DIA EuroMeeting in Amsterdam, Miguel made a statement that “The remote trial model is like the Internet, it’s here to stay.” and advises other companies to get on with it and figure out how to best work with this model. I can confirm from our engagements with many other companies, that is exactly what many others are also doing.

I had an opportunity to interview Miguel and ask for the latest with virtual trials. Here’s a summary of our discussion:

Miguel Orri, Pfizer

Me: You’ve conducted this end-to-end trial, so it seems that there are no regulatory obstacles to operationalize this model? 

Miguel: I have to say there are regulatory hurdles. We got end-to-end because we chose a phase IV study with an approved drug, with a well-established safety profile in a condition where patients don’t die. That made it much easier for the regulators to approve it. It’s very distinct circumstances where these kinds of trials can be conducted. You have to do a case-by-case assessment. What would help is regulation around the telemedicine laws, which are not designed for clinical trials, but something we need to adhere to in a clinical trial setting. This is in a way contradictory, because there are prescription laws, which make sense, but they are not relevant to clinical trials. The telemedicine laws, on the other hand, don’t differentiate between a clinical trial or regular setting.

Me: So is the biggest challenge in the way drugs are delivered to study participants? 

Miguel: It depends on the country. For example, in the USA and Germany, a doctor is not allowed to prescribe medicine without having personally seen the patient. If you consider the dispensation of the study drug as ‘prescribing’ medicine, then they’re not allowed to do that. There is no clear law around that.

Me: What about using the treating physicians instead of investigators? Would that solve this issue? 

Miguel: That’s one way we wanted to go around it. If the GP has seen the patient, then there are escape clauses in the telemedicine law that allows other physicians to carry on the treatment of a patient if another physician has seen them. Another thing, however, is that the GP’s can’t become investigators and they should only be doing things that they are trained to do, such as taking a blood test or checking medical history. If you wanted them to check for the eligibility of the patient for a clinical trial, then they become investigators and the whole concept falls down. You need to have a clear line. We also discussed this line with the regulators and even to them, it’s not clear where this line is. It’s a very grey area.

Me: What are the major issues preventing companies from adoption this model? Is it regulatory, lack of expertise, other issues? 

Migue: Like always, it’s a combination of issues. You need someone to become a champion for it within the company and drive the initiative forward. You need a budget, because the first study won’t be cheaper. You need to set up systems and develop it. Most bigger companies probably want to run a pilot first. Overall I think the potential benefits for the patients and the company are enormous and I encourage everyone to go forward with this.

Me: What kind of performance expectations of metrics does Pfizer have for this model? 

Miguel: The main objective was always to test the whole thing – I call it the “Full monty”, but it is modular and you can take pieces out of it and for example, the informed consent process we developed is better than what is done traditionally and we’re going to deploy this in our conventional studies where you can place the informed consent process in a tablet platform. This saves the investigator time and provides a means of delivering the informed consent materials consistently. They only need a short session together to go over any questions.

Me: Why not do this remotely from home? 

Miguel: You could, but often patients are recruited when they are already at the site so it’s easy to just give them the tablet to study right there. It doesn’t take that much time.

Me: Did you see any performance metrics in your previous trial? 

Miguel: The data quality was very good. We had front-end edit checks, for example, when the patient entered their date of birth, this was then compared against the age field to make sure it’s consistent. If you enter a new drug without an adverse event the system asked why you entered a drug without an AE. Normally this happened at the end of the study and doing it up front saves an enormous amount of queries. We reduced the query rate from 30-40 queries per patient to about 4,5 queries in this study. It’s an enormous cost and time saving. Someone had calculated the average cost of a query as $70 and when that is multiplied by a large number of patients, it’s a large amount [~$2,450 per patient].

Me: Pfizer used a combination of different technologies in the REMOTE trial. Do you see any gaps in the available technology and what would the ideal system look like? 

Miguel: To be honest, I didn’t think that at any point the technology was the limiting factor. It was more the fear from the industry that the regulators would be opposing this. In fact, it was the other way around and the regulators encouraged us rather than restricted us. What I think still is to come is the ‘Clinical Trial App’, which you can just download into your phone and have the whole trial right there. Last time I checked, the US mobile phone penetration was about 65% and it’s likely have gone up [mobile penetration is 100%+, smartphone 53% as of Jan 2013]. With such a tool, it would be possible to connect biometers to it via Bluetooth and also support this with visiting nurses.

Me: Nurses would visit patients at their home? 

Miguel: Yes, when you need accurate measurements of blood pressure, etc, you can’t just leave it with the patient.

Me: So which modules do you think will bring the best value to companies vs. the effort and risk involved? 

Miguel: I think replacing the visits with patient entered data. If you have a 5 year study, you don’t really need to see the patient every month just to see that they’re still alive. You could do that using such an app. The cost savings in monitoring, patient travel, site commitment and patient convenience are great.

Me: So in the future, do you believe such tools will in the future boost patient recruitment rather than inhibit it? 

Miguel: I think, greatly. It’s becoming standard as well. It depends on if you see the future. If you look at the children today, they are already using these devices to communicate even if they sit in the same table. I see this happening with my kids.

Me: I know the feeling. My kids think email is old fashioned and everyone just communicates through social networks and instant messaging. I can reach my kids easier by messaging them in Facebook than trying to speak to them.

Me: What recommendations would you have for other companies interested in doing this? 

Miguel: I would encourage them. Like I’ve said, this model is here to stay and will to some extent become standard. I’m not saying that all studies will be virtual, but all the data quality elements, the improved electronic informed consent, all that is here to stay and not going to go away. Better get ready.

Me: So what still needs to happen before this model can be fully operationalized? This was a pilot for Pfizer, what is needed to scale it up? 

Miguel: We are already looking at the next studies. I don’t think there is necessarily anything missing. It’s just building the confidence that it can be done safely and the recruitment part of it needs to be fine tuned. We need to get networks up, national databases up and running. It’s important to know where your patients are. The CPRD (Clinical Practice Research Datalink) in the UK is a great example. They already have 8% of the population in the database. The ones that have the biggest databases will be the leaders in recruitment. It’s also important for protocol development if you could integrate these systems so that you could run feasibility tests in them.

Me: There are also these initiatives such as the EHR4CR that are looking to make Electronic Health Records available for clinical research purposes.

Miguel: Yes, it’s all happening.

Thanks to Miguel for the interesting talk and for championing this initiative in the industry!

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