So basically, phase four comes and physicians come to people like me who work for the pharmaceutical industry and say, I'd like to do a proof of concept. Or I'd like to look at all the pregnant women that come into my multiple sclerosis clinic because I've seen a trend that pregnant women don't have exacerbations of multiple sclerosis when they're pregnant, and I would look to, like to look at why that might be. So phase four trials can mimic phase one, and there's nothing wrong with that. Phase IV trials can mimic Phase III, which are very large scale, multi-center trials, and in the beginning of time, they thought that maybe those were fake trials, because. Sorry, I forgot to take the mouse with me. [LAUGH] Because in the beginning, remember we always talk about those types of studies, how we design them, and statistically? So, they can be really, really large multi [UNKNOWN], double blind, placebo control, fantastic trials. They can look at pediatrics, which is a pharmaceutical manufacturer. That's where the bulk of our time in phase four is spent. So, you go get the adults, you go get the population that can take the damage. And then you have to go prove that it's safe and nice in those little bitty babies, which scares the bejeebies over anybody. Go ahead... >> Are there any advantages to testing in the pediatrics? >> Use-, used to be. There used to be what was called, patent exclusivity. You would get six months or a year and a half of patent extension from the FDA and the US Patents Office. But they took that away. So now we're not only expected to test it in children. You know, all those antibiotics, they want that up front. So in fact the company that I work for right now, we filed our pediatric label at the same time that we filed our adult label. Mmm, the FDA decided we didn't have enough children under the age of thirteen enrolled. So as part of our phase four, right now. Right now you see out lay children, stanfords, miltild children center, two of my sites here in California. we're trying heavily to recruit zero to two years old and two to five. Because we need at least 30 patients in that age range to give to the FDA, and they, they give you a deadline. [LAUGH] Yeah, so. >> The FDA, does the FDA make you report all of your, all of your findings? >> Yes. I am going to get to that in another [LAUGH] slide, actually. Because they think that we're just doing marketing with that. So, what did I, I wanted to tell you one more thing about phase three. Oh, pharmacoeconomics. So, in the age that we work now, I, I've never seen so much demand for pharmacoeconomic data as I did in the past two years, probably. It's really taken an uptick. So those big, large insurance companies are wanting you to go out and prove that your drug is not only safe and efficacious, but cheaper than the standard of care. So if I am, a, if I am myself, my, my drug is used, it has over 200 off-label uses. It's indicated in three disease states, one of which is primary immune deficiency syndromes. There are 6,145 primary immune deficiencies. If you take it down to the nitty gritty. You know, some of those syndromes have maybe a 100 patients a year that get that. So, I can, in essence, spend all my time doing clinical trials and all my money. Or, I could just give to Blue Cross Blue Shield one trial in the, the most common, common variable immune deficiency syndrome. Which maybe has all of you in this room could possibly have. So, time and money. Time and money. Responsibility to the FDA. >> And one thing to keep in mind with that, when you're looking at pharmacoeconomic trials. Again, looking at the promotional lens, is how you want to talk and how you want to promote that later. If you haven't shown that you're comparable to another product. You cannot say, our costs are different, or we can affect this, we can affect your bottom line, Mr. HMO. Because according to the FDA, the first requirement is to show equivalence. So that throws a kink into all of these, how you design these trials. Because they don't think that equivalence is shown until you have a phase three level kind of design, in, in your study. >> And phase four trial design's very different than phase one, two, and three. So you have all levels of bias. We've listed out for you the most common types of phase four trials. And without going into the, the crux of all the statistics, they're listed from worse to best in how you would rank your clinical trial design for phase four. I like to do cohort studies get a little bit of a, a raw deal. You can take in orphan diseases. History, historical controls. What happened to the normal population or of this disease state in the literature back in the '60's. And compare it to the standard of care today. And I would offer that that might not be the best trial design. But for an orphan disease state, that might be as good as what you can get. So, keep that in mind. So Katie was asking me, do I have to report all my data? And that's a wonderful question, because before, we would just give you, let's, you want to look at if iPhone use by your ear causes cancer? I'd give you $20,000. See you, thank you. You want to look at iPhones and if it causes cancer, I'd give you $50,000 just to tell me it doesn't. And no one every reported their data, and they didn't publish it. So what happens now is back in the 80's we had I think the statistics say that only 25% of the data was being reported and so now we have greater than 80% of all pharmaceutical monies are reported on this website www.clinicaltrials.gov. It's a great thing, we talk about falseness in advertising, let's talk about falseness in clinical trials. You want to talk about physicians that are going on sailboats. You know and talking about all this give somebody $150,000 to run a clinical trial and never make them publish their results. That's mismarketing. and, and there's something also called the Sunshine Act which Katie knows probably more about it than what I do. I, I have to enforce it. She probably knows the ins and outs of it, but basically, you know there was the day where the pharmaceutical rep walked into the physician's office and handed them a mug, and a calendar, and a poster. They might leave behind some text book and these things, you know, half were good, half were bad, right. Well, the Sunshine Act now states that I as a representative of the pharmaceutical industry, not a drug rep, but a representative of the industry, if I would like to take Katie to dinner I have to get her license number, her address, the state she's licensed in, if she's a federal employee and she has to sign a form that says that I have taken her to dinner and I have to report that dollar amount. And my company is now responsible to report to Congress how much money I spend on every physician in the United States. >> And there's limits. >> There are limits, and they change from state to state. State of Massachusetts, you cannot spend more than $5 on a physician for a meal. state of Minnesota, I think it's $20. California doesn't participate. but there are five states, and one state said it, it can be an average meal, like $60, for dinner. So literally, I now have to police myself and the physicians from abusing the system. Because for so many years they got used to abusing the system. >> And this does not just in, incorporate what is spent on them for a meal. You also have to notify and post on your websites now any money you to give to them and to a physician for a clinical trial. >> And if they speak for you as an expert, or if they are a consultant on a panel as an expert. And there are limits to the amount of physicians that the FDA will allow you to have on a panel as an expert. And there are limits to the dollar amount you can pay them. The cap at Pfizer was $150,000 a year to any one physician in totality. >> And that's going down. >> And I was going to say, and that sounds like a lot of money actually. [LAUGH]
