FDA Concerned About Lack of PI Oversight in Early Phase Clinical Trials

In part one of this interview Dan Sfera from The Clinical Trials Guru, speaks to Andrea Charles from Pharma IQ, about the big trends making an impact in clinical research, the FDA's concern over the lack of PI oversight in clinical trials and getting involved in phase one studies.

Pharma IQ: What really big trends you are seeing in clinical research?

D Sfera: It's definitely outsourcing, outsourcing and more outsourcing.  And before we start, I should say I'm not the real guru.  Most of the source of my knowledge comes from the guests I've interviewed on my podcast.  But with that being said, the trend seems to be outsourcing.  And I try to ask the same question to every guest I have on, and that is by far the biggest trend I see.  And it's outsourcing from a strategic standpoint between pharma and the CROs, so no longer are the CROs merely conducting the trials on behalf of pharma but they're also sharing the risks and the rewards. 

For example, let's say there's a successful blockbuster drug created, the CRO now gets a share of some of those rewards.  And they also share in the risk, so they have to put up some of the cost for developing the drug.  So what we're seeing is a whole lot of these special contracts after service agreements between the pharmaceutical companies and the CROs, and that is trickling down to the CROs having special contracts with their preferred research site. 

Pharma IQ: What are the specific challenges that arise in conducting phase one studies and what additional skills are required?

D Sfera: So that would be the efficient patient recruitment. There were just tonnes of problems that we've seen lately where the CROs just do not understand how to target, how to properly target the study volunteers that they're looking for.  And we're seeing a lot of the CROs and research sites attempting to get into the social media space, which is something actually I did not talk about earlier.  That's a plausible alternative, but it needs to be done the right way.  So if there's any innovation that should be done it should be in the marketing and the business-to-consumer side of things. 

And us in the contract trial industry, those of us that have direct contact with study participants, we're not only B2B companies where we market and promote ourselves to other businesses, we're also B2C companies where we promote ourselves to our customers or our consumers, which would be the study participants.  So there's a bottleneck there as far as instant recruitment. The other bottleneck would be positioned PI recruitment.  A lot of PIs were forced to close down their doors during the last several years because of the recession, so the lack of adequate financing and also just the lack of studies that were going around in 2008... between 2008 and even as early as 2012. 
And finally, these master site agreements between the CROs and the research sites, there's been a lot of consolidation, a lot of bigger companies buying smaller companies.  And so these mergers are still being integrated as we speak, so that's another bottleneck that will need to resolve itself over the course of the next few years.

Pharma IQ:
What are some of the barrier to participants in early phase clinical trials?

D Sfera: To participate in a phase-one trial you've got to be between a certain age group.  Often times they're looking for even specific ethnicities because they're doing ethnic bridging studies.  For example, here in California they're doing a lot of studies where they're only speaking to healthy Japanese males between 18 and 35.  And there's other examples of where they're speaking to not only specific age groups and specific genders and obviously healthy, but specific ethnicity.  So it's sometimes very difficult to get into these phase-one clinical trials if you're a study participant.  And the requirements seem to be getting stricter every year.

Pharma IQ: How are CROs normally involved in phase 2  to 4 studies getting involved in phase 1 studies?

D Sfera:
So what you're seeing is either the big CROs buying up some of the phase-one clinics, phase-one companies and transforming them into a CRO themselves sometimes.  I've seen this happen a lot, without mentioning names.  Other times they just find a group, a research clinic in the area that they're comfortable with that they feel can perform an adequate job of a phase-one trial and they sign these master service agreements with them, kind of what I mentioned before, where they're using their own preferred site network.  So the CROs are either organically getting into the phase-one stage or they're just acquiring these niche companies that specialise in the phase-one studies.

Pharma IQ:  What are some of the compliance issues for regulatory inspection and what are you seeing?

D Sfera: Yes, there's a lot. The biggest one, I just interviewed a guy on my podcast.  His name is Patrick Stone.  He's been a pharma FDA auditor for over ten years.  He's a proud producer of our programme.  Patrick told me the biggest issue for compliance is PI oversight or the lack thereof.  So the FDA is just really looking at this issue with specific interest, particularly the lack of PI oversight.  And they actually issued new guidelines up to a few years ago, which specifically outlined what the FDA is looking for out of a PI.  And yes, the principal investigator is allowed to delegate whatever he or she wants to delegate, but at the end of the day their responsibilityis the PI.  So the PI oversight is one of the biggest issues that researchers have to face.

Pharma IQ:
How will NDA approval rates be affected by regulatory changes?

D Sfera: It's still unclear, so is the bottom line.  But, as we've seen with India, much of the data that was done there for several studies, without mentioning the CRO's names, were just thrown out the window. They were unusable, and that was because of the FDA as well as the Indian regulatory.  So you're seeing a lot more care and a lot more scrutiny definitely for every clinical trial, and also with the FDA adding more resources every day towards development.  So for a long time they've had many resources on the food side and now they're adding many more to the drug development side.

Pharma IQ: What are the potential challenges and opportunities of using biomarkers and when do you think is the optimum time to start development? 

D Sfera: I just had a guest who talked about this very topic the other day, Darshan Kulkarni.  He's an FDA attorney as well as a pharmacist.  He talked about biomarkers a little bit, and this is in regard to, sort of, the trend for medicine to become socialised, at least here in the US, and also worldwide.  And so we're going to see a lot more studies with biomarkers and biosimilars as well.  So whether this is a good or bad thing as far as innovation goes remains to be seen.  And I guess Darshan Kulkarni argues that it's a good thing for innovation.  A lot of my colleagues in the research clinic community feel like this is real special innovation.  So it does remain to be seen.

But what we do know and what is almost certain is that there's going to be a lot more studies focused on biomarkers and biosimilars.

Pharma IQ: What do you think will be the game changer with respect to clinical trials?

D Sfera: The game changer,  it remains to be seen, but from what I have gathered during my interviews it really is an agreement between the CROs and the research clinics.  So more and more CROs, because, like I mentioned before, they're partnering with the pharmaceutical companies, they're definitely more... they have more skin in the game.  They're sharing more of the risks and more of the rewards.  So they're hand picking their sites, their research clinic to perform their studies for the next five or ten years, and this is going on as we speak.  So if you're a new research clinic it's still not too late to prove yourself to one of these pharmaceutical companies.  But I definitely think in the next five years we're going to see 80% of clinical trials being done through the first site.

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