Hi, I'm Dr. Neil Bhatia, Director of Clinical Dermatology at Therapeutics Clinical Research in San Diego, California, and I'm going to be giving an overview on managing contracts and budgets, kind of doing a one-on-one for clinical research trials, and taking us through a little journey on how to navigate some of those difficult issues that come along with running clinical trials. And that's me. How do you see everybody? And these are my disclosures. I really don't have anything. I'm not an employee of an eligible company, and I'm not making any patient recommendations, but I will recommend this book by my friend, Dr. Adnan Nasir. It's basically the Bible and the beginner's manual, if you will, of clinical trials in dermatology. I think it's essential for anyone who's doing clinical research to have this book handy as well as to refer to some of the work that a lot of us have done, and not just to learn what to do, but to learn what not to do. So I think that's very helpful. I think the number one strategy is to not market clinical research unless you really are have your feet on the ground and know what you're doing. It's good to have clinical trials in your practice, but it can be very complicated, very different from patient care, and it should be in harmony with a private clinic, but it also should be separate. A good clinical trials unit is firewalled off, not just from the business end, usually in the physical space as well. And it's also important to, from a marketing side, make sure that patients are aware that if they are in clinical research, they are treated in a very different fashion. They're signing consent forms, they're being paid to participate in the trial, and in most cases there is a placebo or a vehicle arm in a trial that might not offer them treatment if they are looking for just treatment. From the business end of it, it's important to remember about recruiting and converting patients back and forth because that can be very tricky, even though it can also be very good for recruitment and for patient options. It's very important, such as in a high Medicare or Medicaid practice, for example, where patients don't have an option, or in a government practice like TRICARE, that clinical research could be an option for them if standard formulas are not offering what they need. On the other hand, a fee schedule is different in clinical research, which I'll show you. It does not represent reimbursements like we bill for in regular coding. It represents the schedule of events and the procedures performed in a trial. It's also important that your nurses are not always coordinators. Coordinators get special training, they have special certificates, and vice versa. Coordinators are often not nurses or medical assistants, but good medical assistants can be coordinators very quickly and vice versa as well. So an office can benefit from both roles with just a little bit of training and a little bit of quality assurance. And of course, every action and item needs an expense. It needs to be in the budget, whether it be as simple as an alcohol wipe, to as major as a centrifuge or a 70 degree freezer, or anything in between. All of those should be included in a budget for clinical research, as well as the investigator's time and the coordinator's time, which I'll show you. The main thing is definitions. Lawyers have a lot of definitions, clinical research has a lot. IRBs, Institutional Review Board, go to clinical practice, informed consent form, electronic data capture, standard operating procedures, and I'm not even going to say the others because you know what they are. But I will get into the NDA, the CDA, and CTA, where they fit in getting together with a sponsor to do a trial. But in clinical practice, we have covered entities, we have protected health information, we have notice of privacy practices. These are actually also very important in clinical research as well. There's a lot of talk about HIPAA protection in clinical research, important to redact documents as well as not reveal patient identities in many cases. So it's important to learn all these research terms as well as research procedures. So the CDA, the CTA, the NDA, it's more like OMG, right? But again, we have to be careful when we talk about research trials. Everything is confidential and we're signed a confidentiality agreement for a reason. Let's say I'm talking to a friend of mine about, hey, I want to do this research trial for warrants. I got this great idea for this compound and my friend takes it and does a trial with it and runs with it, right? So who wins? My friend obviously does or my soon-to-be ex-friend, if you will. But the more important thing is we have to be careful about what we talk about because these are startups for many people. These are business models that could make or break their futures. And more importantly, these are important confidential procedures that involve people. So again, don't take on research trials that don't make sense, but at the same time, know what you're talking about and to who you're talking to do these things about. So again, competing sites down the street are an obstacle for anybody to do a trial. I know there's a trial on atopic dermatitis that a site five miles from mine are doing. I probably won't take that study because it's going to be difficult to recruit and compete for them. But if a rare dermatosis is harder to recruit but it's important for science and it's a good trial, we may consider it even though it might be difficult. So these are, again, business decisions that go with it. But again, the definitions are important. The NDA, non-disclosure agreement, is just allowing people to talk. If someone's coming in saying, hey, I want to talk to you about a trial, let's sign this document so we agree that we're not going to go and talk about it outside that meeting. So it allows us to talk shop, see if there's an option, see if there's drug development issues that come in, and what's the potential. The confidentiality disclosure agreement allows for that preservation of confidentiality to move forward with the relationship to the sponsor, to talk money, to talk agreement, to talk the trial. But then the clinical trials agreement is the ability to perform the trial. And that's basically more of the contract between the site and the sponsor, that the trial can actually be performed as well as get to work. So it's important to remember those papers. They're usually standard and they're readily prepared by a lawyer or by your own office management, if you will. But there are templates for those that can also be provided for you by the sponsor if you're not familiar with that. This is an example of one that came my way. So the NDA says, let's talk. So the non-disclosure agreement, I redacted this obviously, the data is there, but the important thing is that it protects the confidentiality of the company as well as the parties and identifies them and also talks to them as well. As you see in the sponsored clinical trial agreement, which is last, actually, I should jump to the confidentiality agreement, again, it talks about the institution, you see ours there, you see the, again, what is listed there and allows us to get to work. So it's important to have that ability to get saying, let's talk about this. So NDA says, okay, let's talk in general. CDA says, let's talk about this project and this agreement. The CTA, the clinical trial agreement says, let's get to work. Let's figure out what, how it takes, what is going to be involved and then go from there. So stepwise, it's important as the relationship builds, because if the non-disclosure agreement allows you to talk and you don't like what's going on, you can just walk and that's okay too. So the clinical trials agreement, again, has a lot of components, the study protocol, the conduct of the study, sorry, the ability to conduct a study, investigator details, terms of the study initiation. We'll get into payment terms of budget in a moment, but again, keeping things confidential, keeping patient information confidential, redacting things, as I just showed you, and then releasing only information and names that are important is very essential to the ingredients of the CTA as well. Independent contractors, as well as, you know, again, independent study sites, they all work in tandem, just like an academic institutions or other trial sites. The ability to terminate the trial, the ability to allow for inspections, patient rights and invention, these are all important. And then of course, insurance and subject injury, these are also important to recognize in the CTA. As you see here, this is the protocol clarification letter from the IRB. Once the IRB gets involved, then things, a referee, they get reviewed and they get approved, as you see in the first line, the IRB reviewed and approved the above reference document on your behalf. And then the protocol clarification letters are from the sponsor. Until the site gets on, the sponsor has to make sure the protocol is intact, is worthy, and then can move forward and be signed by the trial sites. And then the amendments are frequent, you know, during the trial, if they have to be. Let's say a trial shifts gears or finds out that something needs to be added or an extra lab test, or they're trying to find a different endpoint, they may amend the protocol just for those things. Getting back to the fundamentals, though, is that clinical research is a business. You know, the negotiation of contract language, the budget components, working with the sponsors, these are all critical to the fundamentals of a contract and a budget that needs to be approved and sent in from the site to the sponsor. This usually works through the CRO as well as everybody else that gets approval of these, including the IRB, as needed. The feasibility of the project is very important. What does it take to run a study? If your study site is a mess and you're not organized or you don't have any coordinators or there's no training, you're probably not going to get a complicated study or may have to be considered withdrawn. There's also a question, can the study be enrolled or is it too difficult? So a lot of that is part of the dynamics as well. Subject recruitment is also very important. How well can you recruit? Are you in an urban area that has diversity or a second language such as Spanish? Our place is about 15 miles from the Mexican border, so many of us who speak Spanish in the office, we can recruit Spanish-speaking patients. We also, again, look to have diverse inclusion of all skin of color as needed. But the main thing is to meet the inclusion and exclusion criteria without thinking about quota. It's more thinking about how many patients with the right disease states that are interested in the trial that consent for the trial will come to your site. That's most important. The quality systems, again, are part of that. The trainings are endless. The regulatory assessments are endless. And the internal QC and quality controls that go with it, they're also endless, but they're necessary to prepare in case there's an audit or an inspection. These are essential, not just for sponsor audits, but also if the FDA comes knocking on your door and you're prepared. Again, from the business side, billing for trials is another galaxy. It's a very different world. Clinic patients, we have E&M billing, we have CPT, we have follow-up, we have everything that goes with billing. There are negotiable fee schedules that are part of the contracts. We change insurance plans. Every individual patient billing is part of that. In research, it's a lot different. There's a sequence and a schedule. Once the consent form is signed, the clock is ticking, and that's until the end of study. Every element of that trial is accounted for as part of that start to end, and all costs and unscheduled events will be reimbursed. If a patient has to come in for an unscheduled visit, they have an adverse event, they need a lab test that couldn't be done, they have to repeat something, that patient will get reimbursed. And by the way, in research, we call patients subjects, which I think is okay. But more importantly is that every little thing involves a budget amendment when that workload changes, when additional things happen. Sometimes we call those pass-through costs, when an additional exam or something has to be done. But again, all of that is part of the entire component of the trial. Then again, any and every element of healthcare execution of the subject's care is in the budget. Like I said, gauze and alcohol wipes, performing a biopsy, sutures, labs, you budget for these and you plan those ahead of time. If a study involves a biopsy, for example, or EKGs, or any kind of procedure, that procedure time or effort is also billed for, as well as anything that could be potentially seen or unforeseen, if you will, in the change of labor. Low-vol budgets, you know, will backfire. You know, we'll find out that, you know, somebody tried to get a budget in that was either too high or too low, they usually get tossed or kicked back. Again, the core data work, however, that has to be accounted for. And that can be overdone for monitoring visits, for example, when they're doing it remotely or patient encounters or what have you. So a good budget means the clinic doesn't work without payment, but every expense is considered. And those basic costs can build up fast. Again, you need a lawyer, an accountant, and regulatory for many of those items. There's time for creating the source, for creating accounts, and of course, for electronic data capture for the trial to run forward. Again, staff needs to be trained. The investigators have to go to meetings, there are kickoffs, there are lab fees that go along with everything, even dry ice has to be accounted for. And then, of course, you run your own pharmacy in the trial site. You store the investigational product, you train on how to document it, you document the dispensing logs, and you document the distribution so you know where the drugs are. Every pill, every cream, everything has to be accounted for. And then there's photography, which is not easy. Some photography is very standardized, some is very random, it's just as important that everyone's trained on photography as well, which is usually part of the sponsor's obligation as well. And then, of course, the site visits, the startup, the site initiation visit, the prequel visits, and then, of course, the monitoring visits, and even occasional visit by a sponsor. So this is a good example of a budget template. These are readily available online. Again, you have the sponsor, the location, you put all those into place as well as the protocol number. And then you have the number of visits, you have the screening and baseline, you have visit one through whatever, and then the end of treatment. You have a budget for unscheduled visits, and it takes time, again, for what those elements cost. The informed consent process, inclusion-exclusion criteria, the complete physical exam, it's Patrick test type. These are all assessments. The physical exam as well, it shows you in the schedule of events when these are supposed to take place, as well as vital signs, and then, of course, which lab tests and, of course, telemetry. Again, with those come your version of costs. I've had many people ask me, well, can you send me yours? I say, I can't. That's confidential. But what you can do is go by what your team, and especially your accounting, as well as what is considered the value of those procedures, as well as the value of these events and the workload, and make those part of the budget. So that is something that you all work on as an individual site. But again, every little thing, as you see on the left, the pharmacokinetic blood sampling, the adverse events assessment, injection of an IP, for example, photography, these all have a budget that goes with it. Most importantly is the patient's, you know, the subject's stipend, which also has to be taken into account. And that goes along here with the non-procedure costs. The physician's fee, the investigator's fee, the study coordinator's fee, drug reconstitution fee, the patient reimbursement, anything that goes along with compliance issues or any expense that's taken on by the site, those have to be incorporated into the budget. And then, of course, the IRB renewals, any archiving, and then the biggest one is, of course, advertising and recruitment. That can be one of the most expensive parts of a study, whether it be online, whether it be a billboard, a phone campaign, a radio campaign, these are all part of what we understand as necessary part of the cost. So again, IRB submissions, regulatory reviews, these can make or break any kind of trial opportunity to participate, so you have to be prepared for those. And again, trainings are important, as well as, again, the concept that time is money. So again, end of study costs can actually really blindside a site and, you know, get very expensive if they're not incorporated. And we joke, we don't like PBMs, you'll like CROs even less if that's the case. So again, having timely payments is important. We've seen many times where a sponsor or a CRO is delinquent on their payments, you know, the startup costs have to be met timely because you have to meet your overhead of the trial just like you do when you run a clinic. And again, the same thing with source creation, all of that takes time. Even worse is when you go through all the startup costs and then the study closes or they stop screening or the study ends and you're left holding the bag after all the work you did to start up and then you didn't recruit or enroll any patients, which is again, that's where you get paid off. So again, the sponsors may propose that payment per subject, or they may look at other costs that go with it. So I know this was a lot, I appreciate your time, I hope this is not confusing to you. I really enjoy clinical research and I think if you're starting it or considering it, I think you will as well. There are a lot of good resources. Best resources sometimes are your friends trying to figure out what to do and what not to do. Look into the book as well and take courses like this where again, hopefully some of those questions can be answered. So thanks for your time, take care everybody.

clinical research trials

contract management

patient consent

confidentiality agreements

budget considerations