 So our next speaker is Mary Simmeling, who's an assistant professor of public health in the Division of Medical Ethics at Wild Cornell Medical College. Mary has a PhD in philosophy from the University of Illinois at Chicago, and her research concentrates on medical and research ethics, particularly on issues of justice, human rights, and organ transplantation. Today, Mary is going to talk to us about conflicting messages about conflicts of interest, reassessing current goals, and the strategies for achieving them. Thank you, Marshall. Thank you, Mark, for inviting me and the McLean family. So, Jerry, thank you for making my talk seem not controversial at all. So the first thing I want to say is that I don't have any financial conflicts of interest to report, except that I'm responsible for overseeing conflicts of interest at Cornell at the Medical College. Which could be seen as a conflict of interest of sorts. I want to talk about four things. First, I want to go over some of the major changes in research funding and the increase in industry funding and decrease in federal funding. The widespread and what I think is increasing distrust in industry and in industry-funded research. Review some of the calls for major reform that have come out in the last 10 or so years. And then invoke a concept related to one of my favorite SIGLAR papers too much too soon to ask the question, too little, too late. And I think it's not too late yet. So first, some of the changes in research funding. You can see in this graph the funding trends from 1953 until 2005. And you'll notice that the arrow is the point in 1980 when the Buy Dole Act was passed. And look at the change in the funding. For those of you who weren't familiar with the Buy Dole Act, the Buy Dole Act not only allowed for but put a mandate on NIH-funded researchers and institutions to commercialize the findings of their research because the NIH was funding all these studies and because institutions couldn't commercialize the findings, nothing was happening with them. So you see a big change right there. And then if we look at the research spending growth from 2003 to 2008, we see the NIH has grown 7% and pharma, biotech, and medical devices have become towers. I'm sorry that the years were cut off this graph. This is from 93 until 2013. And you can see the success rates of funded products at NIH. And here is a different view of this data. And this is actually the total number of grants that have been funded. So clearly there's a big decrease in federal funding and there continues to be an increase in industry funding. But there's also this widespread and increasing distrust in industry and industry-funded research and education. And it's not just from the public. It's also from physicians, physician trainees, and researchers. So the question is, does he who pays the paper call the tune? Let's look at some of the findings from studies on industry-funded research. This study, which was published in 2003 in JAMA, found that 25% of all researchers have received pharmaceutical funding, 50% have received research-related gifts, and an analysis of the 789 articles from major journals found that 33% of the lead authors had financial interests related to their research. I would speculate that that number is probably higher now. If you look at pharmaceutical industry sponsorship and research outcome and quality review, there was an article in 2003 in BMJ that showed that research funded by drug companies was more likely to have outcomes that favor the sponsored product than research funded by other sources, and the difference could not be explained by the reported quality of the methods of the research. A psychiatry journal found, a study found that industry sponsorship and financial conflict of interest in the reporting of clinical trials that reported conflict of interest were 4.9 times more likely to report positive results. The association was significant only among the subset of pharmaceutical-funded studies. Another study in New England Journal in 1998 found that authors supporting the use of calcium channel antagonists were significantly more likely than neutral or critical authors to have financial relationships with manufacturers and more likely than neutral or critical to have financial relationships with any pharmaceutical manufacturers. So these are really looking at the journals. There's been some really amazing research done recently by Aaron Kesselheim and his colleagues at Harvard on these topics. This study is a randomized study of how physicians interpret research funding disclosures. It was published last year in September. And what they found is that physicians discriminate among trials of varying degrees of rigor, but industry sponsorship negatively influences their perception of the methodological quality and reduces their willingness to believe in and act on the trial findings independent of the trials quality. So let me remind you again that the direction our funding is going in is NIH funding is dropping, industry funding is rising, and our physicians don't believe in industry-funded research. What about trainees? Trainees' interactions with industry, I'm sorry this is hard to read, in the column on the far right is research from 10 years ago that shows the shifting attitudes. Trainees' attitudes are also changing and they are becoming more skeptical about industry-funded research and industry relationships in institutions. This is another study by some of Kesselheim's colleagues, Eric Campbell, which was published in February of this year that showed receiving industry-sponsored food or beverages in the workplace and receiving free drug samples, both of which are common marketing practices of pharmaceutical companies, were associated with a greater likelihood of prescribing brand-name drugs, although no association was seen with industry-paid speaking or consulting or with receiving industry gifts or reimbursement of travel expenses. Now this is going to be important and I'll talk about later on. The entire focus of the change in regulations recently was on consulting and on travel, not on gifts or meals. This is hard to read but I'm sorry this is a Department of Justice report about the recent $409 million settlement for marketing off-label drugs came out this year. This is another one that came out I think two weeks ago and this is $2.2 billion that Johnson & Johnson just agreed to pay for off-label marketing of their prescription drugs. So amidst all this it's not surprising that there have been a lot of calls for major reforms. I think that the calls for reforms have resulted in minor changes in regulations and practices that don't really get at the heart of what we need to be doing. This is a 2006 article or a quotation from Jerome Kaiser in the Boston Globe and he said disclosure is nothing more than an excuse to continue business as usual. He goes on to talk about positions being bought. So this is 2006. Some of you may have been paying attention to Senator Grassley's focus on these areas. We unfortunately received a letter from Senator Grassley asking about some of our researchers and so he was focusing on how are the disclosures being made to institutions. What is the pharmaceutical company or what's pharmaceutical industry telling us about what they're paying these people and what are the consent documents and research protocols saying. There were a lot of big findings in this and a lot of big researchers that lost their jobs and were on the front page of the New York Times. So Grassley also wrote to the NIH and asked for an accounting of how they were monitoring studies and what the results they had. The OIG got involved. They called for reforms. They came out and said that they needed to increase federal oversight of grantee institutions to the NIH, provide details about the nature of conflicts of interest, how they're managed, reduced or eliminated, require institutes to forward conflicts of interest reports and receive grants from the federal government. Then the AMA got involved. They put out a report about protecting patients, preserving integrity, advancing health. This was in January 2008. They had some key recommendations also. They said that institutions should develop policies that cover financial conflicts of interest, use a compelling circumstances test, have annual reporting, address institutional COI, a number of things. I think the most important of which is to have a compelling circumstances test. I could talk a little bit more about that later. Then the Institute of Medicine came out. You're seeing how over the last 10 years this has just gotten focused from every single group. IOM said you've got to establish conflict of interest policies, create conflicts of interest committees, prohibit faculty from accepting gifts, restrict visits from industry, and with certain exceptions researchers should not be allowed to conduct research involving human subjects. They've got a financial interest in the outcome. Then in 2011 the NIH or the PHS published their final rule. We had to implement this by August of last year. The changes that they ended up coming out with were they changed the threshold level for disclosure from 10,000 to 5,000. There was a new requirement to report travel information that's reimbursed by any industry. The requirement that additional information is reported to NIH about nations of conflicts. This one really gave a lot of trouble to institutions and it ended up not being much of anything so far. A requirement that we make accessible to the public information about conflicts of interest that NIH funded researchers have. So we were all scrambling to get this in place and ready for, I was ready for the New York Times of course to send me an email, say tell us everything. I was at a WMC conference call a couple weeks ago and at the meeting last year and I think maybe a handful of institutions have received requests. We haven't gotten anything so no one's asked about this yet. And then there's a requirement for retrospective review if you don't report the interest. Other federal changes that are coming and we'll see if this changes how things are going. The position payment sunshine act comes out or is now in place this year. The information comes out next year. What this requires is for industry to report its payments to physicians. Not non-MDs to physicians. And so that's another pot of information that's going to be available. This has not come out yet. However, ProPublica created several years ago the site Dollars for Docs where a number of companies are already reporting what their payments are. So this is searchable. I think I just pulled up New York. They've got 30,206 disclosures for payments in New York. It's payments to institutions and to individuals. They sort them by was it research support? Was it travel? What were they being paid for? Consulting on Arrarium. So this is already available but the other rule has not gone into effect. It's gone into effect and we don't have the data yet. So what the new regulations and the new rules and the push has been for transparency about financial conflicts of interest and to preserve the integrity of research. And I think that that's really important. However, disclosure about financial interests doesn't seem to me as sufficient to do the job we need to have done. And in fact, there's research that suggests that the strategy may have the opposite effect than what we intend. So there's a really great paper by George Lowenstein and colleagues called The Dirt on Coming Clean. The Perverse Effects of Disclosing Complex of Interest. And what they found is that disclosures actually sometimes undermine what we want them to do because people don't know what to do with the information. And I quote from the paper, the paradigmatic example of the person who disclosure is unlikely to help is the medical patient who deals with only a small number of doctors does so infrequently, he's in medicine and enters the patient-doctor relationship trusting the doctor. So this is a really important finding. Lowenstein quotes in his paper, this quotation from the New Yorker where we're talking about Wall Street and being in New York now, I'm close to Wall Street and understand it better. It has become a truism on Wall Street that conflicts of interest are unavoidable. In fact, most of them only seem so because avoiding them makes it harder to get rich. That's why full disclosure is suddenly so popular. It requires no substantive change. Transparency is well and good, but accuracy and objectivity are even better. Wall Street doesn't have to keep confusing, confessing its sins. It just has to stop committing them. So on the one hand we've got this move towards disclosure, either disclosure or just get rid of all financial interest altogether. And then in March of this year, this came out from the Office of Inspector General. This is about physician-owned devices, or sorry, distributorships. And it says very clearly, we do not believe that disclosure to a patient of a physician's financial interest in a physician-owned distributorship is sufficient to address these concerns. So they either have to get rid of their relationship or they have to get rid of the relationship. Disclosure in and of itself does not provide sufficient assurance against fraud and abuse because, and this is a very important line right here, and it really is consistent with what Loewenstein says, disclosure of interest is part of the testimonial. It's why people want to go there, because you think that the person is an expert, a reason why a patient should patronize that facility. Thus often patients are not put on guard against potential conflicts of interest, the possible effect of financial considerations on the physician's medical judgment. So now I want to talk about where we are and whether it's too late and what we can do next. So also in, earlier this year, in February of this year, this article came out in JAMA, which has over the past decade published very many articles against pharmaceutical companies and conflicts of interest. And this article had a very interesting title, Restoring Confidence in the Pharmaceutical Industry. And it's a great piece and I recommend it to you. One of the things that the authors say is today the world is a different place than it was in the past, and we can talk at least for now or skeptical about the credibility of industry sponsored research. Taking critical steps to enhance trust and confidence in companies that sponsor clinical research should help enable the pharmaceutical industry to thrive and in doing so continue to provide important products that improve health. Because remember again, NIH funding is going down, industry funding is going up, and we're getting more and more skeptical about whether we can believe it. So they make some great recommendations. Investigators who are not part of the company, preparation of the manuscript, reporting the study results should primarily be the responsibility of the academic investigators. Data from clinical trials should be made publicly available, and companies should refrain from direct to consumer advertising for some specified period of time after a drug is approved or until post-marketing studies are completed. So I endorse these recommendations and I think we should add to them several more. The IOM report in 2009 had a couple of additional recommendations that were really good to include. And that is that we should publish negative results from industry sponsored clinical trials or not delay the publication. That substantial payments from pharmaceutical companies need to be disclosed, and that settlements should be disclosed for federal prosecutors and industry related to illegal payments to physicians. As I just pointed out, two weeks ago the $2.2 billion settlement by Johnson and Johnson. So in conclusion, I think that we need to change how we do things. We need to make it meaningful and find ways to restore confidence that reflect that. And we should ask ourselves some difficult questions. Like, are our strategies working? Are we achieving our goals? And really importantly, do we have the right goals? We should re-examine the current gold standard practices and establish evidence-based strategies and principles-based frameworks for management and disclosure of relationships. We need to have more meaningful disclosures as part of the consent process, possibly even including dollar amounts, more information about relationships. And I think most importantly to remain focused on why we're doing this, to advance research, to preserve productivity and stand behind the research that we do produce, and to care for patients. Thank you very much. Sure, I'll take questions. Sure, Dan. Well, I think we have more meaningful disclosures. So I don't think we should get rid of disclosure altogether. One of the things that the Loan Sign articles argued for is that when we do the disclosure, we do it now. I'll just say someone who has a consulting relationship with this company and is embedded in a consent document with everything else, people don't know what to do with that information. So it's not that we have to put in a consent form necessarily or describe it the way we do now, but I think that it's not impossible but I don't think the way we're doing it right now is meaningful, and I think it potentially has the opposite effect that we're trying to achieve. So, yeah, thank you for pointing that out. Yes, I think it's a really important question. I would like to comment on your earlier statement, though, about physicians who derive income from their work. I think that I have come to see that some of this is part of their work. I mean, some of the work with industry is part of the meaningful work that's being done at research institutions. It's certainly true at my institution, and so the idea that this is not the appropriate way for people to be earning money or working. I don't know that I agree with that. I think it is part of their work. I think especially with the industry funding of trials more and more there are real partnerships here and that's why I think it's so important to work to preserve integrity and trust in industry partnerships because there are a lot of them and for a lot of our researchers it is part of their work. I didn't mean to work, but they're doing their industry. Okay. You had that fascinating slide where you showed that the big things like consulting don't have the impact, but the little things, the trinkets, the gifts, have the impact. I wonder if you could expand on that a little bit more. So I was surprised by that and what I've read in some articles suggests that people discount the influence that the small things have on them, but they distance themselves from the big things, and so if you're getting a big consulting fee or something you may be more likely to feel like it could influence you, whereas you're not going to think that a slice of pizza at lunch is actually going to influence you, and so they have the opposite effect on you. I'm not a behavioral psychologist, but it seems like that that was what was talked about in the Lohnstein paper, and I think it's particularly disturbing that the regulations really focus on those big things and remain completely silent on the little things, and we're focusing all of our energy where it looks like we don't even need to be spending time. So, thank you very much.