Two Industry Friends On Why Sites Just Need to Be Loved - Bill Taaffe & Brendan Buckley

This week. Brandon Barclay, Ted Cruz, chief medical officer, and Bill taff,

chief strategy officer at affinity health and one of the founding members of Icon join me on the podcast. During this episode, they have an in-depth discussion about the communication chasm between sponsors and CEOs versus cites, and delve into some of the potential solutions from the financial struggles of sites to the problems with decentralized and hybrid trials. Old friends Brendan and Bill share their thoughts about how technology can help the industry move towards a more collaborative future.

Welcome to the podcast and Thanks both for joining me today. Let's get straight to the big question. There is clearly a communication disconnect between sponsors, heroes and sites. Bill, drawing on your extensive experience, what, in your opinion, are the main reasons for this?

Yeah just want to go back to what you said in introduction. You know, technology can help. Clinical trials going forward, and that is correct. But one of the things that is missing when we talk about technology for clinical trials is that sites are being overwhelmed with new technology.

So technology is definitely going to help make clinical trials more efficient and

get accurate data. But we've got to get the sites involved in any new technologies going to be applied. So it sort of gets around to answering what you said, you know, and you'll hear from me many times during this discussion. And the sites are excluded from all discussions on trial designs and technology being used.

And it's mind boggling to me. I've been in the CEO world for 40, 45 years, only on the site side for a year and a half. And I was really surprised at how unsophisticated sites are and how unsupported they are. So the problem to me is when people are planning, they talk about getting the stakeholders involved.

Well, to me, the most important stakeholder is the site. We all need patients. And where do you get patients? You get patients at site.

So sites should be consulted. Supporters loved throughout the clinical trial. But that's not happening. I begin to see some progress where people are beginning to recognize that, Oh my god, have we helped a site or a study would move on and we'd recruit the patients, so.

It's not exactly a communication issue. It's a planning issue. And why sides have never been involved in all the planning is a mystery to me, because you can decide between zeros and firma the best way to conduct this trial, the best technology, et cetera.

And then you go to the site and you find what the site, you know, can support all this new technology.

So it's an inclusion issue for me, and sites have to be involved in the planning and any new technology that's going to be used. Yeah and for many sites, the evidence is that investigators often are one and done. A high proportion of investigators who do I clinical trial find it so burdensome that they never do another. And the burden in most sites, other than those that are almost exclusively set up to do clinical trials,

the burden in general sites around the world is that investigators and their staff tend to do the work of trials as an overhead to their day job.

So they need a lot of support. And consultation and training. And one of the difficulties that I had when I was an investigator and I've been an investigator since the mid 1980s, before many people listening to this podcast were born, the accumulation of different technologies is astonishing. I used to have a photograph of my storage room, which had eight different models of BCG machine, all different for different trials.

And the proliferation of different electronic technologies now is a real irritation. So you could be doing 12 trials as a small oncology unit and you would use 12 different versions of et and 12 different versions of randomization and 12 different. Everything's So it's a big problem. And a lot of the time trials sites are expected to just embrace new technologies and take them in, and nobody actually asks them, what they'd like, or what would be most suitable for them.

Yeah, I understand that that's

a real problem. Sponsors and sites working together at that level. Another problem is finance pricing has really skyrocketed at sites over the last couple of years because of inflation and also the price of labor. So this must leave sites in a constant state of insecurity, but also in turn has a financial effect on sponsors.

Bill, how do you think this problem can be addressed? Well, let me just go back and define the problem, really. It goes back to what Brendan said one and done, and a lot of sites got involved in the clinical trials. They were told they're going to get so much per patient and they said, right, let's go ahead and do it.

Now, a lot of them didn't even look at the protocol and didn't do a proper budgeting exercise. The study started. And extra work was required and they went ahead and did us and then found at the end they lost money and they said this and this was not worth it. A lot of work and we're not doing it again.

And I've been at a number of conferences recently where there's a huge concern about the financial health of sites. The survey, done recently by s CRC, the Society of Clinical research sites and something like 60 70% of study sites are operating on about 6070 days of flow. Now, that's not sustainable. You can actually blame the sites in a way, because they weren't sophisticated enough to actually do a budgeting exercise and look at all the aspects of the clinical trials.

And what we saw in this zero world years ago is that, yes, you put a budget together, you do your exercise when you get the protocol and then you submit it. But what happens in every clinical trial? There are changes and sites are not in a position. They don't have the business acumen or they just don't have the skills to track all the new activities that happen in a clinical trial.

There are protocol changes, there's new technology. And another stat at a conference and this is actually very true because I've heard a number of times that was analysis done, 100 studies and sites left between 40% and 50% of the budget on the table because they did not go back and recover the costs. So the answer is a better budgeting process. And affinity is actually working with a number of groups to put together a budgeting plan.

And we're using affinities actually all see our own people, believe it or not at all, X icon people and we know the process. So we're helping sites put together a better budgeting plan and what we call in the sera world recovery get paid for everything you do. And that sounds very obvious. If I do something, don't get paid for it.

But the sad part of it is we're experiencing. And I give you a recent example of a C rose. I'm sorry we're not. That's your cost of business.

They wanted to adopt a new reporting platform. None of this, if you think about it. We had training and then you had tech support and a lot of sites would accept that. But that's a huge amount of time.

So we're pushing back and they're

pushing back and it makes no sense to me. If they want to us to do something extra, please pay for it. And I'm pushing this. This is going back to my see our old days.

We had the same issue early on. But as we all know today, CEOs get paid for everything they do. The scope changes are a big part of the revenue and it's a legitimate revenue. So the answer is better budgeting and better recovery.

I think there's a fundamental issue behind all of that as well, which is that the sponsors and indeed the CEOs view sites frequently in a very commoditized way. So the site is an organization which signs a contract with the sponsor or the 0 to do particular activities, and they're expected to deliver on that, on that contract. And it's forgotten that trials often are an overhead on them, and very frequently the smaller sites, which are the lifeblood of big phase III studies, smaller sites have real difficulty in maintaining recruitment of staff. So, for example, if one is paid on a per patient basis, how do you contract a study nurse for the duration of a two year study when your flow

is of the order of 60 days?

Now, in Europe, we have a real issue in that there are significant employment laws which. Just prevent hiring and firing of people just on an expedient level. So it's difficult for new sites to come on board, for new investigators to come in and commit themselves to participation in this. And it's fundamentally got to be changed.

Sites have got to be regarded not as a kind of anonymous commodity that can be hired like pork bellies or something like that. They've got to be understood to be the absolute raw material of the trial, and without them, the trials can't continue. Now decentralized and hybrid trials have been talked about considerably in so far as providing a potential solution for some of the issues around patient recruitment. Do you think this could have a positive impact on sponsor site relations, starting with you, brandon?

Well, decentralized trials, I think. Contain very little to the benefit of sites. And in fact, they present significant risks to investigators. So if you look at the fundamental documents which determine how clinical trials have got to be done, I see GCP and the Declaration of Helsinki investigators have very onerous and very clear.

Obligations to participants and trials for their safety. I see HDCP 4.3 and declaration of Helsinki 16 are very well known to ethics committees and IRBs and regulators, but they never appear to enter the discussion and the teams meetings and the webinars promoting the idea of decentralized trials so investigators participate in these at risk of their license and their indemnity insurance if the more remote they are from the participants in the trial. If if you don't have a doctor patient relationship with the participant on the trial, you're increasing your own risk as an investigator.

So I think that's a significant problem. The second thing is that but hybrid trials, who knows what hybrid trial is? They vary a lot in different therapeutic areas. What would be a hybrid phase I trial would be a hybrid phase for trial.

And these are cardiovascular prevention, diabetes versus oncology. So people tend to talk of clinical trials as if they're a homogeneous, unvarying entity. But it's horses for courses. You can do wonderful hybrid trials very efficiently, in particular therapeutic areas, but you can't.

And others often it's not very well understood by those who discuss it. What it is like to be an investigator or a coordinator or a study nurse or indeed a trial participant. And bill, what are your thoughts? Oldie as we said earlier, hybrid trials have been around in some form for a long time, you know, e pros and diaries.

And that was pretty straightforward. I mean, the biggest challenge with hybrid trials is the number of new data sources. And you've now the site is responsible to go back to a brand and the principal investigator is the signature on the 1572. He has responsibility for everything that happens with that patient, whether it's at home or whether it's at the site.

So all these new sources of data are now becoming a challenge, and the FDA and other regulations are beginning. Regulators are beginning to question, well, the way the data is collected at home for one visit, is it comparable to the way data was collected at the site? And there is actually no validation yet of that. So there's questions now

about the amount of data, which is great as you're getting a lot of new data on the patients, but who's going to interpret it?

And the other question is popping up recently. You've got vendors and you've got health care nurses visiting sites and they're entering it into their laptops or tablets. Who owns the data? And that's again, that shall be the investigator, but the investigator.

And this is a big issue. For some sites now, they do not have any say in the selection of the vendor that's going to the patient's home. And I spoke with a number of sites, said I am not participating unless I do due diligence on the third party provider who's going to be involved. And I have oversight of that vendor.

That is not happening. So there is a lot to be said about hybrid trials. It does reduce the burden, but we're also hearing that some patients actually prefer the social aspect of going to the site. And as popped up recently on the study, we were involved and the patient said, I don't want anybody coming to my home.

I don't want my neighbors or my family knowing that I'm in a. A clinical trial. So there are all these issues. And it comes back again.

As I said earlier, I'm going to keep saying this. If you have the sites involved at the beginning, they could tell you the challenges, and they could guide you on the technology and the challenges. Earlier we talked about investigators and one and done. Do you think that decentralized or hybrid trials will make physicians more or less likely to take part in trials?

Certainly, looking back to my 35, 40 year persona as an investigator, I wouldn't have anything to do with the decentralized trial, I'm afraid, because I would be concerned about my legal and professional exposure and hybrid trials. It depends at all. Depends on the trial. There are wonderful ways of doing hybrid trials which minimize inconvenience to participants and make it easier.

There are all sorts of sensible, innovative approaches that one can do with hybrid trials, but it all depends on the trials. So if I were doing a cardiovascular outcomes trial in a new diabetes drug, hybrid is perfect because patients with diabetes are used to measuring a whole pile of things on themselves every day. But if I'm a participant in the non ecology study, I'm really struggling to find other than quality of life data which are collected anyway in all the oncology trials these days, how I can sort of speak hybridize the trial in any way that improves it. And I would like to add here that there's a lot of good things about hyper trials and a lot of good things about the technology that's going to be used.

But everything is moving too quickly, and I think sites will get involved in hybrid trials if they are supported, if they're involved in the beginning, and if they're compensated for all of the time and the training and the oversight and the IT aspect of it, they definitely will. It's in their interest to it's a business most sites in the past as friends that have sort of an overhead thing. But a lot of these small sites, as Ben said, are the bread and butter of these big phase Ii trials. They're actually in a for making money now in reimbursement in the US has become a problem.

Sites see clinical trials as a new revenue vertical, but unfortunately they just didn't know how to budget. But they are beginning to learn. I mean, there's a lot of movement in with groups like

SARS in educating investigators to trying to avoid this one and done. And so, yes, I think sites will embrace hybrid sites.

I don't think the sites are going to embrace decentralized trials, as Brendan said, you know. Everything's at risk here, your license and the signatures of 1572, which can involve federal action against you and your site if you do not comply with the. The 1572 regulations. So to me, it's all about, you know, embracing the sites and telling them what is going to happen up front.

Here's the technology we're going to use. Here's the vendor we're going to use and here's how the data is collected. And what we're seeing is sort of anecdotal, but some of the activities of some of these third party vendors could actually be. Conducted by the street themselves.

So if they talk to the science that we're going to use a vendor for this activity, the site can say, well, hold on, I can do that. And that would be huge. I mean, that would take another party out of the mix. And another source of oversight.

So a long winded response. Until the question. But my answer is Yes. Sites will embrace it if they're supporters and if they get paid.

There's a key word here as well, which is simplification. So basically the way that you get sites to do stuff is to make life easier for them than they already have to endure. If you make life more difficult, they're less likely to participate and to continue to execute the study properly. But making life simple for them,

which we can do now, is really the key to participation, to getting people in as new investigators and sites and keeping them there.

So anything that we in the industry, either as service providers, as sponsors can do to make life easy for sites, is really worthwhile and valuable. But the moment you make life more difficult, you're putting people off. And this is in a context where with the so-called great retirement or whatever they call it, after covid, there are real difficulties in recruiting people to get involved in this kind of activity at all levels across industry. So simplicity is absolute.

King and I think you could apply a yardstick if something you do isn't going to make life easier. And preferably take away things that are difficult. You shouldn't do it. You've talked about the fact that you're positive about the effects of technology on trials, although decentralization is another matter potentially.

Now we have seen rapid uptake of solutions during the COVID era. So if we think about these, how do you believe that technology can support greater collaboration and understanding? I read a white paper recently that was issued by Oracle. Now, obviously, they have a vested interest because they have a product for integrating data.

But I think what they say in there is actually the key. We have new tools, but they have to be able to integrate data collection and data management and also the ability to collect data from New sources. And if a site goes ahead, accept a decentralized, they don't want to have to manage different data sources from different vendors. And the CEO doesn't want that.

And I'm sure the farmer doesn't want that. So we've got to, as a solution for the data side of it, find better platforms where data from different devices and different sources can be integrated. And there's one company, maybe two, that have come up with a

site liaison person. Now, that's in addition to the CRA.

And this one company. I spoke to said, we recognize the burden. We recognize that the site now has a lot more complicated input into the management of this clinical trial. And what's very true is the life of the study coordinator used to be very simple.

The patient would come in, they take the data, enter a DDC. That was it. That was the coordinator job. The study coordinator job today is doing exactly as you said, but also now working with different vendors and home health care people.

And they got to manage business. They got to let the patient know when the visits are happening. They got to take questions from the patients about, you know, what went wrong to visit or they didn't like such and such a thing. Or the sample collection kit that got was the wrong one.

So the study coordinator job

is really changing dramatically, and by having a site liaison person actually helps educate and support that study coordinator. And again, I'm sort of crossing over here a little bit, but Brandon touched on, you know, the staffing issues at sites like anywhere else is an issue. And one of the biggest issues is that study coordinators are not paid as well

as the CRA. And so pharma and zeros see that and they take the study coordinators and then they complain, my study is not going well.

Well, they just take the study coordinator. But if the site recovered all of the costs, they could compensate the study coordinator and they could actually create a nice career path. That is a key issue. You know, the study coordinators job has changed dramatically.

I think one of the things that would help a great deal would be to reevaluate how much futile activity is invested in the trial. So we know, for example, that about from Central watch, about 60% of all monitoring activity has no effect whatsoever on the outcome or the integrity of the trial. And it's a very expensive activity. I think refining what the CRA does would help considerably in allowing them to be much more of a support to sites and to be viewed as

such.

Rather than to be seen as a kind of a policeman of sight. The second thing which astonishes me is that we're one of the few industries which operates very much in the past. So a monitoring visit which goes to a site. Maybe every six weeks identifies problems that have occurred long ago and over which they have no influence whatsoever.

So, you know, you discover that somebody mishandled a toxicity, not according to protocol 6 weeks ago. Well, the House has already burned down. You know, it's too late. So identifying that it happened is one thing.

We need to be much more real time and proactive. So a key to modernizing clinical trials and to getting them. From a state where they're almost identical to the way we did it in 1984 when I did my first one. The way to get that is to suddenly start thinking about real time data and real time monitoring and real time intervention.

So we want the ability for sponsors to be able to see what's happening now in the site's interaction with the participant in the study. Finding out what happened six weeks ago is too late. It's a bit like your fire department coming along and saying, hi, guys, you know, we don't have any fire appliances, but did your house go on fire six weeks ago? If you were in a town in the us, you wouldn't reelect the fire chief the next time around with that.

But we reelect that process in clinical trials all the time. We continue to do it. So knowing what to do 24 hours a day and what's going on in the trial in real time is simple to do with modern technology. But nobody has got around to saying, what are we doing this wasteful?

Let's get rid of it and let's try to get into the real time. Just want to quickly touch on the role of the Sierra and actually. The currency array job as it is in the past series knew everything about the trial. They knew all about the medical aspects, the data collection, the stats.

Today, the c.r.a. is a road Warrior who comes in and monitors source documents and that's ask them any questions about the study. They quite often don't know it. And the most frustrating thing for the site is they tell the c.r.a., you know, we're having issues with this home health care provider.

They're not sending the right people out. They're not checking the right data. The surveys don't even know who's involved. So it's a disarray.

Roll has to change. And the training of the Sierra, I don't as just a road Warrior is actually making it very difficult for the site. They rely on the Sierra as the person who they can go to, but they're now finding out that is not the case, particularly in decentralized trials where there are different vendors involved. Yeah, it's I think back to a previous point you made, bill, you know, if we take away the activities of a Sierra that are traditional but futile and non-contributory, we then make a lot of time for them to be site support people.

Yeah, the alloy of the site rather than somebody at the site slightly fierce and they come and visit could be a much nicer job as well. Absolutely Yeah. The turnover in the Sierra pool is horrendous, 30 plus because they're bored and they get burnt out. I have heard some stories about this, some of the things they've had to do.

In fact, somebody told me that they had to kind of do their work in this cupboard, kind of all the monitoring from their office. It sounded quite, quite hectic. I've also had conversations with site staff on this podcast, and they do say that they're starting to find their voice. So despite all of the problems, there is hope.

And they said that sponsors and crews are beginning to listen more because they realize they can't ignore this communication problem. And during the podcast, we've talked about some of the problems. But on a more optimistic note, have you seen any signs of improvement? Yes, I know the majority of sites I've spoken to say no, there is no real improvement.

In fact, things have got worse. You know, the burden, the site has increased and they're having to fight to get paid for their activities. And that is sad to me. I been in the cities for a long time and I just didn't realize how bad these sites were treated or not supported.

The great thing about having worked in an icon is I can't have been around almost 30 years as icon people everywhere in almost every pharma company, biotech company. So I can easily pick up the phone to a number of people. And I've talked to small biotech companies who immediately. Have put in place site liaison people.

They recognize that. So in these sort, it's anecdotal examples, but they see it and they see the importance and they are taking action. And there's a lot of discussion at conferences. I've been at three strike based conferences since last November, two CEOs.

And one major. And the. Problems and the challenges for cites are being addressed. The last conference I was at was a very good one.

There was a farmer representative, a s.r.o. representative and two site representatives and it was very open discussion and both farm and CEOs recognized that we're doing a terrible job. You know, you guys are the key stakeholders and we need to improve it. So it is being talked about, but it hasn't filtered through yet. There are certainly ways of making life a lot simpler for cites, and we in particular are very focused on that and simplification is a big factor in that.

The other source of hope, I think, is that maybe the decentralized trial issue is a symbol that people are rethinking how trials could be done better. I don't think that is the right solution, but there are other ways, I think, that may be exposed as improvements, which can move clinical trial conduct into the 21st century to the benefit of patients and to the benefit of sites as well. And I think, again, the key is simplification and site satisfaction. If the site likes technology, they need to get that technology because it makes.

Them happy. They will recruit patients to your study and they'll follow them through and make sure that they don't drop out of the study along the line. So I think attention paid to sites really pays off and. Trying not to think of sites in a commoditized fashion is the first step in that.

Yeah, just sort of a crude comparison. But General Motors makes cars and they make cars at the manufacturing facilities, but they have the best technology, the best support, the best facilities, the best oversight, the best management, the best and sop's, because they know if they don't do it, the manufacturer's right, the car that comes out the other end is going to be problematic. The sites are the manufacturing aspect of the clinical trial world, and it's sort of mind boggling to me that, you know, I want to get my drug to market. You know, there's a lot of data around showing that one day lost on the market, it can be $3 or $4 million a day.

That's a conservative estimate. And you don't support sites to get your drug to the market faster. If you don't support this issue, you're going to lose days and your patent and your revenue and see your rules rely on, you know, recruiting patients that they're paid you know, different milestones and many patients who were crucial when the study. The report was finalized.

They need to recognize too that if I support the sites I can get the recruitment done. site will help me retain patients. And later on the revenue quicker. There's a paradox that has always intrigued me, which is that in the course of drug development, the non-clinical bit and probably through into the exploratory phase studies in one and 2 a, they're done under very careful control and scrutiny by the sponsor.

Everything is done to an SOP. They know everything that's happening all the time. And then once the drug is thought to be worthy of continuing further and making a big investment, and because we are now ramping up investment by an order of magnitude, at least, it's kind of thrown over the fence to people whose primary. Business day to day isn't doing clinical trials at all.

I mean, you could exaggerate this and say, well, the early phase of drug development is highly controlled and the later phase it's thrown over the fence to a bunch of amateurs. So it's astonishing that the major investment occurs in the latter stage, where sites suddenly where those who are doing the study are the least supervised of the whole process. Unless supported.