Last week, the NIH ran a workshop to examine the safety of several widely used diabetes drugs called GLP-1 inhibitors and whether a definitive link can be established to acute pancreatitis and pancreatic cancer, which were the subject of recent studies that generated considerable controversy. The outcome was inconclusive, but the FDA may want further studies. Meanwhile, the American Diabetes Association called for drugmakers that sell these meds to release patient-level data that can be used for an independent review (back stories here, here and here). Whether the drugmakers - Merck, Bristol-Myers Squibb, AstraZeneca, Eli Lilly, Novo Nordisk and Boehringer Ingelheim – will comply remains to be seen. With the exception of GlaxoSmithKline, the pharmaceutical industry has resisted releasing such data over concerns that proprietary information will be compromised. But ADA chief medical officer and chief scientific officer Robert Ratner believes they are now on the spot. We spoke with him about this decision…
Pharmalot: Three months ago, when one study was first released, the ADA issued a statement that played down or at least sought to allay concerns. Now you want patient-level data. I don’t know if you would consider this an about face, but it’s certainly a change in tone. What happened?
Ratner: Science is an iterative process and the way science unfolds, observations are made and hypotheses are tested and then it goes through peer reviews and is challenged. It takes a long time to arrive at the truth and the goal is always to provide accurate information to scientists, clinicians and, ultimately, to patients. As evidence accumulates, we need to deal with it and we deal with it in a whole variety of ways. And part of it is to critically look at data and ask if it is accurate and appropriate. Has a study been done with sufficient rigor? And how do we interpret the data? And that was part of the statement following (the first study). The statement a week ago is in recognition of continued press and controversy over the role of pancreatitis and pancreatic carcinoma. There’s an enormous amount of opinions flying around. Our goal is to develop a system in which we can take a look at the data that are available.
Pharmalot: Of course, patient level data is not something most drugmakers seem to want to provide. What are your expectations about receiving that kind of data?
Ratner: We want maximal transparency and a maximal degree of data to make rational judgments about the veracity of the data. I’m very encouraged that we’ve had public commitments about working with us in this regard. You’re absolutely right - we’re asking a great deal and part of it is to maximize public confidence in what is found. We’ve not heard from some companies, but they are considering a response, but all involved have expressed support for what we’re trying to do. We simply have to wait and see to the extent to which we’re going to be able to do all this.
Pharmalot: How hard do you think you’ll have to work to get this data?
Ratner: I think we’re going to get it. In conversations with industry representative, the questions we’re discussing are the format of data, transmission process of data, whether data is going to be sent to us or supplied through a distributed data network. We’re getting down to that level of detail… There’s a huge problem with looking at mean data from a whole variety of different studies and trying to make any sense out of them. On the other hand, when you can utilize patient level data, then those analyses take on much greater power.
Pharmalot: Of course, ADA is not FDA. You have no authority to make this happen. What happens if one company doesn’t participate? That lessens the impact, I imagine.
Ratner: That’s one of the benefits. We can act as honest brokers. That’s our intent. We’re not being judgmental or going into this with a preconceived notion. We want to release a request for applications for independent observers to analyze the data. We will not be doing that. The ADA serves a function of supporting independent research. And that’s how we view this - as an independent assessment of these raw data to come up with objective findings. Once we have the data, we will be providing data in its entirety to investigators who have been vetted by our research review committees, who are capable of doing such analysis…. I do think there is a bully pulpit that we can actually speak to about the need and necessity to do this. The example you provided - if one company refuses to participate - Does this impact the outcome? Yes, it probably would impact to a certain degree, but it would look awfully bad for that company to refuse when others have (agreed). I want to be able to use this collaborative approach and we stand is where we fall, depending upon what the data show and that‘s the way research ought to be done.
Pharmalot: Some will say the ADA is not an honest broker because industry funds are accepted for various reasons. What do you say to that?
Ratner: I can assure you that when we support research, the ADA does not influence and does not censor the results of the research. That’s why we consider it to be independent. The results of the independent assessment will be presented and published as they find them. And if, in fact, that upsets and industry representatives, so be it. We’re willing to live with that. Everyone is willing to go into this with eyes open and we don’t’ know what the truth will be, but we all want to find the truth.
The process in which we support research is that a request for application goes out and there is a period of time for independent investigators to submit proposals. We have standing as well as ad hoc review committees – over 400 individuals who volunteer their time to review grant proposals and provide priority scoring and then a decision is made based on their budgets and our budget. It’s all according to priority scores. So we have multiple layers to ensure objectivity in the process.
Pharmalot: How long you think this will take?
Rartner: My hope is that we’ll have a complete analysis a year from now. At scientific sessions next year, we can have the definitive analysis presented. We‘re hopeful we’ll be able to announce who is funded for this research before the end of the year. This is as fast tracked as it can possibly be.
Pharmalot: Meantime, what should physicians and patients make of all this?
Ratner: There’s a level of controversy and powerful opinions on both sides. I think health care providers and patients need to speak with one another. If patients are doing well on these medications, they should not discontinue without speaking with their physicians. For those considering initiating therapy, the health care providers should read the literature… It all comes down to risk versus benefit.