Let Google Solve Our EMR problems

The Wall Street Journal reported today that Google was going to launch their own operating systems for PC's competing with Microsoft's dominant Windows platform. Google seems to continuously creating new, innovative and useful products. This very blog is hosted on blogger, which is now a Google product. Since they seem to be doing such a good job, why not let them solve the electronic medical records problem?

EMR's are a big part of President Obama's health care plan. I certainly value the use of EMR's. They provide me the data I need when I need it. They allow me to communicate more effectively with my staff. Using e-Prescribing in our EMR I am able to fill prescriptions faster and more accurately for my patients. Finally, through our EMR, patients can communicate directly with their physicians. (We use Touchworks by Allscripts. I have no vested interest in the product or company)

However, I do not believe that EMR will really save a lot of money. Time is money, and EMR's do not save time. EMR's do improve quality of care. They allow you to do more in a given amount of time, but do not save time., and in fact may add time because you can do more. The best example I can give for non-EMR users is that just in the way that your email and Blackberry have not saved you any time from the days when you relied on phone calls and the US postal service (have they not instead created more work?), EMR's do not save time. Politicians point to cost savings in preventing duplicate work. There might be a few duplicate tests or procedures prevented, but likely not that many and not nearly enough to call investment in EMR's a cost-reducer.

In my post $19 Billion For Health IT-Money Well Spent? I also call into questoin how the stimulus package is funding health IT. Looks like that money went to hospitals to improve exsiting systems, and not to help the primary care physician offset the HUGE cost of implementing an EMR in his or her practice. The software, hardware and support needed for most EMR's cost far more than the average physician practice can afford.

The real issue with EMR's is interoperability. The are many companies that make many products and not too many systems talk to each other. In our hospital alone, we now use up to eight different computer systems to store and retrieve patient information. Your primary care doctors EMR should be able to talk to the Pharmacy's computers, the lab's computers, the hospital's computers, the radiologist's computers, the specialists consulant's computers, etc.

Regardless of whether you support a single payer system or a tax rebate for patients to purchse their own health care; wouldn't it make sense to have one really good EMR that every doctor could use? Wouldn't it be great if this was on a web based platform, meaning that all you would need is a computer (or netbook, or web based mobile phone) and a high speed internet connection and you could have access? Most docs already have that. Wouldn't it be great if interfaces could be created so that all parties "spoke" to each other? Wouldn't it be great if this system could include functionality so that patients could communicate with their physicians, request appointments, and see their lab results?

Who better to create this EMR than Google? The interoperability/interface issue stems from the fact that there are so many proprietary systems. Each company that makes an EMR wants its EMR to be used by everyone. Just throwing money at all of these companies is not going to solve the problem or make EMR's more affordable or usable. The goverment already has a pretty good EMR used in the VA. It works well inside the VA, but doesn't talk to others. Even in a single payer, government run health care system, would you have the goverment re-vamp the VA EMR? Why not go to the pros at Google? They have already started the process with Google Health, though this is a personal health record and not an EMR. They good create a Google Medical record (GMR) that interfaces with their existing Google Health platform. Sure, they would have a monopoly, but in this case the benefits to the public, patients and doctors far outweight the risks. If the Google EMR was supported by the goverment, then you could create restrictions to limit any of their profit.

Lantus and Cancer- A Closer Look Is Not Reassuring

Kevin MD brought up the issue of Lantus and cancer on his blog, linking to both my original post which stated that patients should be concerned, as well as a post from Amy Tenerich at Diabets Mine who takes a more conservative approach, like the ADA and AACE. ( I do question the motivations of these groups in my recent post on this matter: Lantus Causes Cancer! Why Doesn't Anyone Seem Care? ). Some responders to my inital post felt that I had not read the studies correctly. Therefore, below is my detailed interpretation of the four studies recently presented which caused the controversy.

The first study was a German study of 127,000 patients, which 20,000 were treated with Lantus. Most of these patients had Type 2 diabetes. Overall, this study found a correlation with all insulins and cancer, but no difference between the analogue insulins. However, because patients on combination analogue and human insulin were excluded in the study, the dose of lantus was much lower than the other analogues. The researchers then adjusted for insulin dose, and they found a dose dependent relationship of cancer and Lantus. The magnitude of this effect was such that 1 cancer might be caused for every 100 patients taking Lantus for a year. One of the limitations of the study was that it was not possible to break the analysis down by types of cancers caused. Given this and other possible limitations, the editors of the journal decided not to publish this study until these results could be replicated in other studies/countries, especially considering the importance of the findings if corroborated.


Since then 3 other studies were performed, and subsequently all four were published together.



The second study was a Swedish study matched a national cancer database and a national diabetes database looking for a connection. This study included over 120,000 patients of which about 6000 were on Lantus. They found no increase in risk for cancer with Lantus when taken with other kinds of insulin. These patients were younger, and more likely to have type 1 diabetes. However, analysis of patients who took Lantus alone, most of whom had type 2 diabetes, showed a doubling of breast cancer, which was highly statistically significant (though no increase in other types of cancers).


A third Scottish study used national database registeries similar to the Swedish study and they found exactly the same thing. The patients who took Lantus with other insulins, who were generally younger type 1 diabetics had no increased risk of cancer with Lantus compared to human insulin (actually had lower rates) but the patients on Lantus without other insulins, mostly older type 2 diabetics had a higher risk of cancer. There was also similarly an increased risk of breast cancer in women taking Lantus alone, which was about the same magnitude as the Swedish study.



The fourth study looked at cancer risks associated with a range of insulins. This retrospective UK study looked at over 62,000 adults that were started on oral agents and/or insulin. Diabetes developed in adulthood, so these were mostly type 2 diabetics. In general, the study found no difference between human insulin and analogue insulins like glargine (Lantus). However, the study did find that metformin use is associated with a lower risk of cancer, and seemed to abolish cancer risk. Also, only 10,000 patients in the study were on insulin, and only 2000 on Lantus. Plus, it was not clear who was taking meformin plus Lantus. Thus, given the very small number of patients on Lantus, some of who may have been taking metformin, this negative finding is not all that reassuring.

Taken together, in my opinion, these 4 studies strongly suggest a link between new cancers in adult type 2 diabetics who are taking Lantus alone. Now, we can't say that Lantus actually causes cancer. In fact, it is unlikely that Lantus actually causes cancer alone, because it takes years to develop most cancers. However, it is more likely that Lantus causes existing cells to grow and divide more rapidly. Usually, the body's own natural cancer fighting abilities take care of these cells. In other words, though Lantus may not cause cancer, adult type 2 diabetics taking Lantus seem to develop clinically apparent cancers at much higher rates (double for breast cancer) then those not on Lantus. Though whether or not Lantus is causative of cancer is an interesting academic discussion. However, from the patient's standpoint if taking Lantus increases the likelihood they will develop cancer, that's all they need to know.



Large observational studies are far from perfect. The can detect differences (i.e. adult type 2 diabetics taking Lantus were more likely to get cancer), but can detect the reasons for these differences. The only way to show actually causation would be a very large, randomized control trial conducted over years. However, this will take years to complete. The Europeans are suggesting meta-analysis of even larger databases to find out sooner.

Until we know for sure, given a possible risk for Lantus increasing the rate of cancer development, I would suggest it would be prudent to stop taking Lantus if you are a type 2 diabetic, especially if you are not taking other kinds of insulin. Detemir insulin (Levemir) is a reasonable alternative. Though it has not been studies as extensively, its effect on the IGF-1 receptor (the purported mechanism of the cancer association) if much, much less than Lantus.

Lantus Causes Cancer! Why Doesn't Anyone Seem Care?

The answer is probably money, but more on that later.

I recently posted on the Lantus/cancer connection in my post A New Problem With Insulin: Cancer. The concern was triggered in a press release about a recent European report based on one earlier and three new studies which show a link between Lantus, a long acting insulin, and cancer. As I mentioned, I though it was interesting that more alarm has not been raised, particularly here in the US. Nissen's poorly done Avandia study got major press, and people stopped taking the drug (He was recently proven wrong- see here fore more info). Yet, for Lantus, the report is not about one study, but four studies that show similar findings that Lantus increases rates of cancer. In addition there are some biologically plausible reasons (more later) and a clear dose response. If you look at the criteria for causation, the Lantus/cancer connection seems to ring true. Yet, there seems to be not that much in the press and little public outcry to pull the medication from the market. This may be in part to the fact that the news cycle is now 24/7 Michael Jackson, but other medical stories, like the FDA and Tylenol, seem to be getting some attention, so this can't be the entire reason.

What do the experts say? The Europeans are making "an urgent call for more research". Yet, the US response is much more subdued. The official response from the American Diabetes Association (ADA) stated that findings from these research papers are conflicting and inconclusive, and cautioned against over-reaction until more information is available. A similar response can be found from The American Association Of Clinical Endocrinologists (AACE), the smaller but more academic group of diabetes specialists.

Where is the media attention on this? Where is the warning to patients? Why doesn't anyone seem to care?
MJ aside, here are some reasons:

1. The US experts don't want to say too much because of their ties to the drug companies. Both the ADA and AACE receive huge amounts of money from corporate sponsors, specifically the drug companies. In fact, back in 5/07 the experts issued a joint statement that had similar comments on the Avandia scare (which turned out to be correct). Sanofi-Aventis, the maker of Lantus, gives money to both of the ADA and AACE, and their members are unlikely to bite the hand that feeds them.

2. Though not all endocrinologists think alike, based on national and international diabetes recommendations, the expert guidelines recommend the use of insulin in type 2 diabetes much sooner than I would recommend. I have blogged in the past that I believe the endocrinologist making these recommendations may have a conflict of interest in that they have an incentive to make recommendations that will lead more patients toward insulin is because insulin use in type 2 diabetics is how they make their living. It is possible that the endocrinology experts are cautious about scaring the public about Lantus, because this may cause concern about all insulins, which they believe is the best treatment for diabetes.

3. The reason why Avandia drew more attention is because Dr. Nissen and some Congressmen were the ones making the noise, not the specialty societies. The Nissen meta-analysis on Avandia, from the data analyzed, to the publication, to the media frenzy had political motivations, whereas the Lantus studies do not. (See a timeline of the politics of the Avandia study in my post Diabetes Conspiracy )

What now?
Thanks to a comment on my previous post, I looked into the matter a little more. One of the problems with insulin is that is that it is related to insulin like growth factor (IGF-1) which has been shown to stimulate tumor growth. Regular human insulin has some affinity for the IGF-1 receptor, but Lantus has a much greater affinity, which is the likely reason more cancers were seen. There happens to be another long acting insulin on the market called Levemir that has very little affinity for the IGF-1 receptor (less than even human insulin) and is as effective as Lantus. In 2008, Lantus just missed the top 25 most commonly prescribed branded drugs at #26 with over 10.25 million prescriptions that year. Levemir came in at #170 with only 1.3 million prescriptions. Though I doubt this is public knowledge, I would guess that Novo Nordisk (the company that makes Levemir) is not giving nearly as much to these organizations as Sanofi Aventis (makers of Lantus), but I could be wrong. Since Levemir is a newer drug, is was not included in these studies and one can not rule out potential harm. That said, its low affinity for IGF-1 is reassuring. Thus, upon further reflection, I think that all diabetic patients who are on Lantus should talk to their doctor about insulin use, and if they need it, ask their doctor to consider switching them to Levemir.


Update: Via Med Page today, FDA just announced they were going to look into this. Not sure how much press this will garner. Certainly more valuable use of their time then trying to take down Tylenol.

A New Problem With Insulin: Cancer.

Followers of this blog will note that my approach to the management of Type 2 diabetes is different then currently recommended guidelines. Unlike current recommendations which seem to push insulin after the failure of two older oral agents (which are known to fail), I recommend that multiple agents be used, reserving insulin as a last resort. I have blogged before about my concerns with insulin (The Problem With Insulin , The Problem with Insulin- Part 2 ). While life-saving for all type 1 diabetics and many type 2 diabetics, insulin causes many problems including the need to frequently monitor finger stick glucose, costs, inconvenience, weight gain, and hypoglycemia which can lead to death.

However, a new concern regarding glargine insulin (trade name Lantus) seems to be emerging. This press release best explains it. In summary, a recent study confirmed earlier findings between increased rates of cancer in diabetes taking glargine insulin and regular insulin, in particular, a doubling risk of breast cancer.

Why might this be true?
Human and even porcine insulin has a long track record of safety. However, glargine insulin is different in that it is not "natural" but a manufactured insulin, specifically modified to last longer. While insulin has been used for decades, glargine has only been used since 2000. Other reasons to consider this more than just a concern include that the findings are reproduced in multiple studies of tens of thousands of people, and that the finding seem dose dependent. In other words, the higher the dose of glargine one takes, the higher the risk of cancer. In order to know for sure, we need a randomized, controlled trial of thousands of patients to prove this is the case. This is exactly what the European Diabetes Association is calling for. However, those findings will not be available for years.

Why be concerned?
Most guidelines for type two diabetes recommend that long acting insulins be started first, and most clinicians usually start with the synthetic, glargine type of insulins. In fact, the preferred regimen for insulin in type 2 diabetics by most endocrinologists is a combination of a long acting insulin like glargine given once a day with very short acting insulins (lispro) at meal times. This approach, called basal-bolus, is supposed to mimic what the pancreas naturally does. Though I am glad that the European endocrinologists have raised concern and are calling for more data, I find it interesting that more alarm has not been raised, particularly here in the US. One very poorly done study which has now been proven to be false, caused so much uproar that people simply stopped taking Avandia. Yet, study after study shows a compelling and dose responsive relationship between glargine and cancer, and there seems to be little in the press.

What should you do?
If you are on Lantus, don't stop!!!! Please discuss this with your doctor first. There are other options other than Lantus, and even with an increased cancer risk, Lantus still may be the best option for you. If you are diabetic, but not yet on insulin, first do everything you can to avoid this. First and foremost, diet and exercise are key and critical. If that doesn't work, in addition to lifestyle changes, consider using multiple pills before resorting to insulin. If injections are needed, talk to your doctor about the incretin mimetics, like Byetta as alternatives to insulin. Studies of shown that in patients who failed diabetes pills, Byetta performed similarly to glargine in controlling diabetes but with less hypoglycemia and weight gain.

Why aren't medical students taught about health care policy?

Happy to have been interviewed by and mentioned in this very timely article at Slate.com which asks the question "Why aren't medical students taught about health care policy?"

There is so much to cram into 4 years of medical school, it's hard to imagine that we could teach students more. However, some basic understandings of health care policy are needed. Students need to know a little about policy because:
1. The way medicine is practice is (for the most part) dependent on how health care is paid for, which comes from health care policy. In primary care, we need to rush and see patients in 15 minute slots not because we want to, but because we have to see that many patients to make ends meet. The medical home is one of many policy solutions that might fix this.
2. Policy makers listen to physicians, especially when we tell them what is good for patients (and not just our own interests). Having a voice is really not that hard. Through minimal participation in medical societies, like the America College of Physicians for Internal Medicine (my specialty), you can get behind those who share your opinions and can go up on the hill and fight for you.
3. Students in particular need to know about policy that regards to work force issues. Though we have a shortage of physicians, with calls to expand medical school class size, there is not likely going to be an increase in residency slots. This means that it is going to be much harder for students to get into the lucrative specialties they might desire.

I am very proud of some the initiatives we have taken at our institution, including bringing the entire 3rd year class to the Hill. However, we need to do more to incorporate policy into the current curriculum (and we will0>

The Avandia Scare: Why it Matters, Who's Responsible, and What to Do

We now know that Avandia is not associated with increased cardiovascular risk.

I have blogged quite a lot regarding Avandia. You might ask why would I so strongly support and blog about a drug/medication that, even if it doesn't seem to cause heart attacks, is expensive and is known to have other side effects, like congestive heart failure and bone fractures?


Here's why:





Why it matters?


1. Patients, doctors and the public were unnecessarily scared. You only need to recall the story of the boy who cried wolf to know why false alarms can be problematic. There were many patients who were unnecessarily worried that the medication their doctors prescribed might be killing them. Similarly, physicians were worried that a medication they thought they were giving their patients to help them, might have caused harm. The reaction can be seen in the precipitous drop in Avandia sales. However, it wasn't just that patients stopped taking Avandia and switched to its competitor Actos. Though there are now far many more prescriptions written for Actos than Avandia (was about 50/50 before the Nissen article), the entire class of TZD medications declined. Also, though there were increases in other drugs like metformin, many patients simply stopped taking their diabetes medications, and many of those patients did not tell there doctor about this. (We have documented this in our large, academic faculty practice and are in the process of publishing the results).




In addition, the Avandia scare was probably one of the key events that prompted the FDA to start warning the public about issues they were looking into BEFORE their analysis was complete. I blogged about this in March, 2008 in my post More FDA warnings should not be cause for worry. Thusfar, all of these "early warnings" have not panned out, and have undoubtedly scared more than a few concerned patients. Spiriva and Stroke? Doesn't' seem to be associated. Singulair and Suicide? Well the FDA just released their findings and though the label to Singulair was changed, the data does not seem to support a major concern, and the FDA's concerns were significanatly downgraded from the original warning. In other words, asthmatic and COPD patients on these drugs would have never needed to worry about these "warnings" if it wasn't for the Avandia scare.

This is not to say that we shouldn't take adverse effects of drugs seriously. Vioxx taught us that lesson. The Vioxx scare made everyone take a careful look at drug safety including the reporting and approval process. However, the Avandia scare added unnecessary fuel to the fire to the point of hysteria. Now, many patients will question the necessity of every medication a doctor prescribes. This itself is not inherently bad (an activated, inquistive patient is a plus), but it's the fear that causes this questioning that is problematic.

2. We need Avandia (and medicines like it)
Most diabetics are not able to be controlled on only one pill. In fact, of the two older, generic pills; we know that most patients on these medicines will eventually fail therapy. Analysis have shown that though both metformin and sufonlyurea lower blood sugar; about half of all patients taking either of these medications lost diabetes control by three years, with the vast majority losing control at 9 years.

Avandia, was the first medicine to show that it could keep patients' diabetes under control. The ADOPT trial showed that Avandia, a thiazolidinedione or TZD, substantially reduced loss of diabetes control compared to both metformin (Avandia 32% better) and sufonlyurea (Avandia 63% better). TZD's work by reducing insulin resistance, and also can improve beta cell dysfunction. Both effects were seen in ADOPT. The recent RECORD trial has now also showed this effect. Actos, another TZD, also seems to do this as well. Finally, some of the newer DPP4 medications like Januvia and (hopefully) soon to be available saxagliptin (Onglyza) have shown to preserve pancreas beta cell function in animals and human studies are only now just getting under way.

The point is that though the older medications are needed, they are not enough. Newer medications like Avandia have value, most importantly keeping blood sugar under control and preventing the need for insulin.

3. Patients were harmed.

The damage done to patients from the Nissen publication is hard to quantify, but in addition to unnecessarily worrying patients, patients were definitely harmed by this poorly done study and the subsequent media frenzy. As mentioned, many patients simply stopped taking their medications. It is not known what ill effects this might have caused. More importanly, those doctors who stopped using the TZD class altogether likely started prescribing more and more insulin. We now know from both RECORD and BARI 2D that not using TZD's like Avandia can double to triple the amount of patients needing insulin. Though the exact number from RECORD is not published, based on the what was presented at the ADA, I calculate that it takes at most 10 patients treated with Avandia for 5 years to prevent at least one patient from needing insulin. Put another way, for every 10 patients who stopped Avandia, one likely needed to go on insulin. Based on pharmacy data (via drugtopics.com, thank Mr. Medsaver) , there weree 11,331,000 prescriptions for Avandia and 11,329,000 for Actos in 2006. In 2008, that dropped to 3,103,000 and 12,518,000 respectively. Assuming that both Actos and Avandia prevent the need for insulin, and assuming that about every 6 scripts written represents one individual patient, over one million diabetics likely stopped taking Avandia or Actos, and thus the Avandia scare likely caused over 100,000 type 2 diabetic patients to need insulin, which could have been avoided.

Patients don't like insulin. There is the cost of not only the medications (most doctors are using the newer, expensive insulins, not the older ones), but also the strips and the machines to check blood sugar. In addition, patients fear low blood sugar, or hypoglycemia, which can be fatal. I have blogged about The Problem With Insulin (as well as The Problem with Insulin- Part 2)

4. The entire approach to the way diabetes is managed has forever changed.

Dr. Nathan, an endocronologist from Harvard, is basically the current architect of the ADA's guidelines for the management of type 2 diabetes. In a Perspective piece in the New England Journal of medicine , he shows that he does not like new diabetes medicines stating that newer diabetes drugs like Avandia and Januvia , "are generally no more potent, and often less effective in lowering glycemia, than the three oldest classes (insulin, the sulfonylureas, and the biguanides), all of which are more than 50 years old. Moreover, the newer classes are uniformly more expensive and are associated with adverse effects."

Despite the results of ADOPT, in an early guideline, Nathan stated that TZD's were merely a secondary option. In the newer consensus statement, mostly because of the Avandia scare, he further pushes for the older medicines (metformin, sulfonylurea, and insulin) as the preferred medications to use, leaving Actos as only a second line alternative, and taking Avandia and Januvia off the map. Though not all endocrinologists necessarily agree with this approach, many primary care physicians follow what the ADA recommends. In addition to TZD benefits presented at the recent ADA meeting, there are other examples of gains for diabetic patients, specifically saxagliptin, which is now proven to show no cardiovascular side effects and may even prevent strokes, and once weekly exenatide (Byetta). This insulin before newer medications approach, which is promoted by Nathan and the ADA is, in my opinion, not good for patients.

5. It is now much harder for ANY new diabetes medications to be availble for patients.

The Avandia scare had another MAJOR impact. Because of this supposed risk of increased heart attacks, the FDA now requires ANY new diabetes medicine to prove that it doesn't cause heart attacks. I talk about this in more detail in Rough Times for New Diabetes Drugs: The Diabetes Conspiracy Part III. This finally came to fruition several months ago when allogliptin got it's approval delayed. (This is somewhat ironic since alloglipitin's maker is Takeda, who also makes Actos, Avandia's competitor. Takeda was banking on alloglipitin more than GSK was counting on Avandia for it's future, so even though many docs switched from Avandia to Actos, it is possible that in the long run, the Avandia scare will hurt Takeda far worse than GSK).

6. The false alarm was motivated by politcs, ego and greed. Not all false alarms are bad. However, there is a difference between someone yelling "fire" when they smell smoke, and the school boy pulling the fire alarm to get an earlier recess. Prior to the Nissen meta-analysis, no one thought that Avandia would cause heart attacks. In fact, if anything, the thought was that TZD's like Avandia might actually prevent heart attacks. In fact, in one of Nissen's own studies Actos (a competitor to Avandia) was shown to decrease the progression of plaque build up. (Yes, this might be a conflict of interest if Nissen is attacking a drug whose competitor funds his research). To further describe those who may have less than pure motivations, see below.




Who is to blame?

1. There is no questio n that cardiologist Dr. Steve Nissen is in part to blame. He is very smart and an excellent researcher. He knows that some of the techniques he used in his analysis were not up to par, such as excluding any Avandia study where there were no heart attacks from him analysiss. There are many flaws and critics of the this meta-analysis, as well as an alternative analysis that found completely different results.

2. The New England Journal of Medicine is also to blame. This is one of the most prestigious medical journals. To ensure the studies they publish are of the highest quality, they use a process of peer review. This means that when a study comes into a journal for publication, the editors first look at this to see if it is of interest to the journal and if so, sends it out to several experts in the field. These experts comment on the study, and based on these comments, the journal chooses whether or not to publish. Before publication, the author needs to address the comments by the peer reviewers and re-submit to the editor. This process generally takes several months. The New England Journal released the study to the public in just 3 weeks after Nissen submitted it. It seems impossible to me that The New England Journal followed it's own policies, especially with such an important, confusing and flawed study. The study was so confusing that one of the reviewers contacted GSK to make sense of the data (this was a major no-no, and the doctor got a lot of negative publicity about this move, but the point is that one of the experts could not make sense of a study that was published in just 3 weeks). Had the peer review process been followed strictly, the study may never have been published or the results would have been modified and likely gotten much less publicity.

3. An FDA insider. Until the Nissen publication, Avandia had known potential problems with heart failure, but no one was thinking about risk for heart attacks, and if anything possibly preventing heart attacks. Even if Nissen has combed through all of GSK's data on his own, now publicly available thanks to Eliot Spitzer, finding heart attacks with Avandia would be like finding a needle in a haystack. The only folks who knew about the problem were the FDA, and they decided not to release the data to the public, because other data was contradictory. The fact that 42 studies (not all the same) were used in both the Nissen and FDA meta-analysis seems more than just coincidental. I have no actual knowledge of any communication, but I strongly suspect that someone inside the FDA tipped off Nissen to the data that GSK submitted to the FDA, because they did not agree with the head of the FDA's decision not to make this data public.

4. The FDA in general.

The FDA made the right decision to hold off on any conclusions regarding GSK's surprising meta-analysis, since it knew DREAM and ADOPT would soon be published and there was no problems with RECORD study currently underway. When the Nissen paper was published in the NEJM , the FDA could have come out strongly stating it's reasoning for not acting on GSK's meta-analysis, and because by this time ADOPT and DREAM were published and showed no increased cardiovascular risk, the FDA could have clearly shown why their decision was right. In addition, another opportunity for the FDA to make a strong statement reassuring the public came the following week when the RECORD interim analysis also showed no increased cardiovascular risk. Instead, the FDA just bent over and took the criticism from the media, bloggers, Congress and others.

What should be done?

Because the Avandia scare caused unnecessary worry for doctors and patients, harmed patients, forever changed the way diabetes is managed, and made it more difficult for new diabetes medicine to be approved; because we need medicines like Avandia; and because the motivations behind the Avandia scare may not have been in the best interest of patients; something must be done. I believe a full investigation is in order, starting with the FDA. I would like to know whether Nissen communicated with anyone inside the FDA that leaked confidential information. I would also like an investigation into the New England Journal of Medicine. Though we do have freedom of the press, medical journals must be held to a higher standard, since doctors use information published in these journals to make life and death decisions. If the New England Journal has policies in place to ensure only high quality data is published and they did not follow these policies when publishing Nissen's study, they too should also be held accountable. I have sent emails to the Department of Health and Human services. I hope they respond.

Comparative Effectiveness Can Be a Win for the Drug Companies

One of the Obama administration's major initiatives as part of health care reform is comparative effectiveness. Currently, the drug and device companies do almost all of the research. NIH and other government agencies don't often compare which treatments work best and the industry usually only sponsors studies that it knows will make their product come out on top. Thus, it is not surprising that many drug companies do not support this comparative effectiveness. However, their position may be misguided.

A great example of comparative effectiveness was just presented this afternoon at the American Diabetes Association and simultaneously published ahead of press in the New England Journal of Medicine. The trial is called BARI 2D and is a 5 year comparative effectiveness study in over 2,000 type 2 diabetics sponsored by the good old USA (via NIH). In this case, the drug companies won not just once, but twice!

1. Drugs beat interventions. BARI 2D was designed to look at two things. First, in patients with type 2 diabetes who have atherosclerosis (blocked heart arteries), do they do better with interventions like surgery (coronary artery bypass) or percutaneous coronary intervention (where the cardiologist goes in with a catheter to open up a blocked artery with a balloon, often leaving a stent in place) or no interventions and just medications. Previous studies had shown no difference between medical therapy and intervention for stable patients, but the question remained whether or not this would hold true for type 2 diabetics, who are at even higher risk for heart related events. However, the same results were seen. Optimal medical management (think lots of pills) is better than angioplasty and bypass surgery. If I was the head of a drug company, I would be pretty happy with these results.

2. New medicines beat (sort of) old medicines. The second question BARI 2D tried to answer was whether the greatest benefit in this very high risk group of type 2 diabetics would come from insulin providing medicines (insulin, sulfonylurea-which are older drugs) or insulin sensitizing medicines (metformin, and thiazolidinediones or TZD's, which are newer). Again, there was essentially no difference in the primary outcomes of death or major cardiovascular events.

Having the old drugs show no difference then then newer drugs might at first seem like a loss for the drug companies. However, severe hypoglycemia was more frequent among patients assigned to receive insulin provision than among those who received insulin sensitization.This is important, because severe hypoglycemia is bad, and can be life threatening. Even more important, at the 3-year follow-up, the most frequently used drugs in the insulin-provision group were insulin (60.7%) and sulfonylurea (52.0%); in the insulin-sensitization group, the most frequently used drugs were metformin (74.6%) and a thiazolidinedione (62.1%- of which most (55%)was rosiglitazone or Avandia). Specifically, the use of insulin was double in the insulin providing group. If you can achieve the same results without using insulin why wouldn't you? My patients don't like taking insulin. The strips are expensive, checking your blood sugar frequently has been proven to reduce your quality of life, and I already mentioned severe hypoglycemia. This is a loss for those drug companies that make insulin products, but a real win for those drug companies that make pills and other newer insulin sensitizing products. Finally, more than half of the patients in the insulin sensitizing group took Avandia and virtually none took it in the insulin providing group. Guess what? In this group of type 2 diabetics who were at extremely high risk for death and heart attacks, there was absolutely no difference. Thus, BARI 2 D trial confirms what the RECORD trial clearly showedjust the other day: there is no cardiovascular risk associated with Avandia. This is a win for GSK (makers of Avandia) and Takeda (makers of Actos, another TZD).

BARI 2D represents comparative effectiveness at work. It tells us that we should be using medicines (even if some of them are expensive) instead of doing angiography and surgery (even more expensive) in certain patients who are commonly using the later. BARI 2D also shows us that newer (even if some of them are expensive) insulin sensitizing drugs provide equal cardioprotective benefits, but less hypoglycemia and less need for insulin which has many costs associated with it. The drug companies should re-consider their stance on this issue. If they are making novel and useful products, comparative effectiveness will likely be a win for them.

ADDENDUM- In the middle of writing this post, the Wall Street Journal published Diabetes Study Questions Expensive Treatments on this exact same issue. However, they got it wrong on Avandia and Actos. These medicines were shown to provide better sugar control, less hypoglycemia, and less need for insulin. It was indeed disappointing that there was not a statistically significant reduction in death or cardiovascular events. It is possible that longer studies would be needed to show this effect. However, even with no difference in the primary outcome; better glucose control, less hypoglycemia and less use of insulin is a win for these medications, not a loss.