We are releasing our latest research today.
In August 2011, we conducted a research study of 21,344 social media conversations on Diabetes and 18 oral diabetes medications that were posted from March 12, 2000 to March 23, 2011 across all blogs, user forums, and message boards on the Internet.
The purpose of the study is to understand how patients talk and feel in open conversations publically available on the Internet about Diabetes and the oral medications that they use.
This study examines at a high level the patient-reported effectiveness and perceived safety of 18 oral medications used for the treatment and management of type II diabetes.
We provide insights into patient opinions about each drug’s performance based on the personal experiences that patients may or may not share with their physicians.
The results are interesting to say the least. Feel free to download:
http://www.woollabs.com/odms.html
Wool Labs is working to develop Phase IV/V programs to look at safety and efficacy of products through the lens of how patients report performance and experience. We already work with clients as well as publish our own research on how patients discuss their diseases and conditions, medication, and safety and efficacy measures. So the point to this blog is to explore this concept further.
Thursday, December 1, 2011
Wednesday, September 14, 2011
Does J&J and BMS's Xarelto have a second chance for approval?
After a tough time in the early part of last week, on September 9, 2011, the FDA panel green-lighted Xarelto after FDA staff rejected it. FDA staff reviewers felt that Xarelto did not prove safety and efficacy for stroke prevention against Coumadin in the 14,000 Afib patients studied. But the FDA panel seems to see the data differently. The American Heart Association is also advocating Xarelto's approval.
Xarelto is already approved for prevention of clots in knee and hip replacements but in our data, cardiologists were skeptical in using Xarelto in their afib patients. And as treatment is likely for life, their concerns have a huge potential impact on their patients. There is no doubt that Coumadin/warfarin has problems but they are known problems and physicians seemed concerned about swapping known problems for unknown problems. And it seems that these specialists are expecting liver and/or bleeding problems with Xarelto
After reading a few transcripts of the FDA hearing, there do seem to be a few key issues that seem to need to be worked out even if approval is granted:
1. Some see that warfarin was not as skillfully used in the Xarelto pivotal trial, ROCKET, as opposed to other trials which makes it harder to evaluate Xarelto's comparative performance.
2. There seemed to have been a reasonably high number of discontinuations during the trial which made it hard to understand how to transition patients to another treatment from Xarelto.
3. Optimal dosage is not clear. Some panelists felt that twice-a-day dosage might be better than once-a-day.
Everyone did agree that the trial was well-designed and executed. But to me that makes the results more murky. One would think that a good trial would answer questions like this. And while the panel voted 9-2 for endorsing the drug, it was not resounding support. There are some that support efficacy parity with warfarin but not superiority. Is that enough? It could be if Xarelto's safety profile was stronger than warfarin.
One thing to remember is that anticoagulation is extremely complex and there may not be any completely solid answers to the outstanding issues. I do believe that if approved, many cardiologists will not be rushing to use the drug until more real world experiences can be reviewed.
A final FDA decision is due in November.
Xarelto is already approved for prevention of clots in knee and hip replacements but in our data, cardiologists were skeptical in using Xarelto in their afib patients. And as treatment is likely for life, their concerns have a huge potential impact on their patients. There is no doubt that Coumadin/warfarin has problems but they are known problems and physicians seemed concerned about swapping known problems for unknown problems. And it seems that these specialists are expecting liver and/or bleeding problems with Xarelto
After reading a few transcripts of the FDA hearing, there do seem to be a few key issues that seem to need to be worked out even if approval is granted:
1. Some see that warfarin was not as skillfully used in the Xarelto pivotal trial, ROCKET, as opposed to other trials which makes it harder to evaluate Xarelto's comparative performance.
2. There seemed to have been a reasonably high number of discontinuations during the trial which made it hard to understand how to transition patients to another treatment from Xarelto.
3. Optimal dosage is not clear. Some panelists felt that twice-a-day dosage might be better than once-a-day.
Everyone did agree that the trial was well-designed and executed. But to me that makes the results more murky. One would think that a good trial would answer questions like this. And while the panel voted 9-2 for endorsing the drug, it was not resounding support. There are some that support efficacy parity with warfarin but not superiority. Is that enough? It could be if Xarelto's safety profile was stronger than warfarin.
One thing to remember is that anticoagulation is extremely complex and there may not be any completely solid answers to the outstanding issues. I do believe that if approved, many cardiologists will not be rushing to use the drug until more real world experiences can be reviewed.
A final FDA decision is due in November.
Tuesday, September 6, 2011
FDA says that J&J and Bayer's Xarelto has insufficient safety and efficacy data
Xarelto is the anticoagulant pill from J&J and Bayer. It was supposed to be a major blockbuster and compete with Pradaxa from Boehringer Ingelheim. Now analysts are saying that it might end up as a third line treatment behind warfarin and Pradaxa, if it even gets approval. The FDA is looking for more safety as well as more efficacy data in the prevention of stroke among Afib patients. Ouch. I think this is a big hurt for Bayer.
The market seemed surprised as the FDA seemed more upbeat about the product back in July.
Lovenox, which was the branded gold standard, is off patent this year so new products were highly anticipated. Coumadin/warfarin has been used for decades but it has bleeding, stop/start and food interference issues.
Having three drugs so close together in approval (Pradaxa, Xarelto and apixaban) was actually amazing since no new drugs have been approved since Lovenox.
Now, we did a review of anticoagulation back in October 2010. So looking back at the study, we did see evidence that cardiologists were critical of Xarelto's data and were worried about liver and non-major bleeding problems in their Afib patients. So I guess I am less surprised than others on this one.
At the time, we reported being less than enthusiastic with the data ourselves. I really am not a big fan of warfarin, mostly because physicians like to put patients on it for life and it restricts them so much in terms of having an active life. But is has been used for decades so anything replacing it really needs to be more safe and more effective, IMHO.
The market seemed surprised as the FDA seemed more upbeat about the product back in July.
Lovenox, which was the branded gold standard, is off patent this year so new products were highly anticipated. Coumadin/warfarin has been used for decades but it has bleeding, stop/start and food interference issues.
Having three drugs so close together in approval (Pradaxa, Xarelto and apixaban) was actually amazing since no new drugs have been approved since Lovenox.
Now, we did a review of anticoagulation back in October 2010. So looking back at the study, we did see evidence that cardiologists were critical of Xarelto's data and were worried about liver and non-major bleeding problems in their Afib patients. So I guess I am less surprised than others on this one.
At the time, we reported being less than enthusiastic with the data ourselves. I really am not a big fan of warfarin, mostly because physicians like to put patients on it for life and it restricts them so much in terms of having an active life. But is has been used for decades so anything replacing it really needs to be more safe and more effective, IMHO.
Wednesday, August 31, 2011
Expensive targeted therapies are on the rise. Does cost ever play a role drug treatment? I think we are going to have to deal with this soon.
As the pharma and biotech industry moves towards more targeted therapies, cost of treatment increase dramatically. The latest cancer drugs are targeted to specific DNA sequeneces and mutations and their costs can be over $100,000 per course of treatment. They also might only extend life for a few months. However, expensive and targeted treatments have given some patients years.
Avastin, which lost its approval for breast cancer, is one of those extremely expensive treatments. Patients and even oncologists do not like losing treatments even if they do not seem to work all of the time or even predictively. Patients on Avastin were horrified to lose the drug's approval and it was heart-wrenching to read their stories.
But does cost play a role in the delivery of US drug treatments? It does in other countries.
Does stronger efficacy and more precise patient stratification make very expensive drug use more defensible? Targeted therapies are supposed to be just that, targeted to a particular marker and theoretically they don't work as well or at all in the absence of that marker. But patients report being on Herceptin who do not have HER2+ breast cancer. And we see that there are lung cancer patients on Tarceva who do not have have the EGFR mutation. Sometimes after patients fail on other treatments, we do see the use of targeted therapies in untargeted ways. Should they be if there is no evidence that they would work?
Unfortunately Avastin lost its approval because it was considered to be ineffective and Genentech could not explain why the 17,500 women who found the drug valuable were different. Why does Avastin work for some patients and not for others? If the brand knew that then I think the FDA would have allow the drug to keep its approval for the right patient and people would have been less likely to call out the death panels.
Development of more targeted drugs is a trend on the rise. So astronomical cost for treatment will be on the rise as well. Do we demand more patient stratificatoin and then make everyone stick to it? What is fair to the patient and what is fair for everyone else?
I think we are all going to have to really deal with these issues in the very near future.
Avastin, which lost its approval for breast cancer, is one of those extremely expensive treatments. Patients and even oncologists do not like losing treatments even if they do not seem to work all of the time or even predictively. Patients on Avastin were horrified to lose the drug's approval and it was heart-wrenching to read their stories.
But does cost play a role in the delivery of US drug treatments? It does in other countries.
Does stronger efficacy and more precise patient stratification make very expensive drug use more defensible? Targeted therapies are supposed to be just that, targeted to a particular marker and theoretically they don't work as well or at all in the absence of that marker. But patients report being on Herceptin who do not have HER2+ breast cancer. And we see that there are lung cancer patients on Tarceva who do not have have the EGFR mutation. Sometimes after patients fail on other treatments, we do see the use of targeted therapies in untargeted ways. Should they be if there is no evidence that they would work?
Unfortunately Avastin lost its approval because it was considered to be ineffective and Genentech could not explain why the 17,500 women who found the drug valuable were different. Why does Avastin work for some patients and not for others? If the brand knew that then I think the FDA would have allow the drug to keep its approval for the right patient and people would have been less likely to call out the death panels.
Development of more targeted drugs is a trend on the rise. So astronomical cost for treatment will be on the rise as well. Do we demand more patient stratificatoin and then make everyone stick to it? What is fair to the patient and what is fair for everyone else?
I think we are all going to have to really deal with these issues in the very near future.
Monday, August 29, 2011
Does Facebook matter for pharma companies the way they think it does?
Over the last few weeks, pharma companies and those who follow pharma have been talking about Facebook not allowing pharma to continue to block comments on their pages. I have been confused by all of the fuss this causes.
Wool Labs has been studying patient and physician experiences and behavior online for a few years now. In the hundreds of studies we have performed, Facebook has never been one of the top 200+ sites that houses or shares influential content for patients or physicians. Never. What we mean by influential content is content that patients and/or physicians read, discuss, comment on, share with others, use to make decisions, and change behavior.
So as far as we can see (as we see very far indeed), Facebook pages do not host deep, involved, well-read, or heavily discussed content consumed by patients and/or physicians who suffer from or follow a particular disease/condition or use/prescribe a particular treatment.
Now, of course pharma-sponsored sites don't allow comments so that explains why their sites don't show up in our studies. But presumably a patient who is discussing his/her condition would allow comments and invite others to share similar stories. And we see those but they are not drawing the thousands or tens of thousands of patients that others sites draw. And those non-Facebook sites are what need to matter to pharma.
Patients and physicians share their experiences all across the Internet from well organized disease-specific communities to personal blogs to seemingly unrelated non-health sites.
So while I think it is sad to see some pharma companies pulling Facebook pages, as I always want to see pharma involved with their customers. I would also like to see pharma put as much effort into studying the rest of the Internet as I have seen them put into Facebook.
It is the rest of the Internet that is screaming for pharma to pay attention. It is the rest of the Internet where pharma can learn what their patients and physician believe and how they choose their actions. It is the rest of the Internet that influences and therefore, matters more.
Wool Labs has been studying patient and physician experiences and behavior online for a few years now. In the hundreds of studies we have performed, Facebook has never been one of the top 200+ sites that houses or shares influential content for patients or physicians. Never. What we mean by influential content is content that patients and/or physicians read, discuss, comment on, share with others, use to make decisions, and change behavior.
So as far as we can see (as we see very far indeed), Facebook pages do not host deep, involved, well-read, or heavily discussed content consumed by patients and/or physicians who suffer from or follow a particular disease/condition or use/prescribe a particular treatment.
Now, of course pharma-sponsored sites don't allow comments so that explains why their sites don't show up in our studies. But presumably a patient who is discussing his/her condition would allow comments and invite others to share similar stories. And we see those but they are not drawing the thousands or tens of thousands of patients that others sites draw. And those non-Facebook sites are what need to matter to pharma.
Patients and physicians share their experiences all across the Internet from well organized disease-specific communities to personal blogs to seemingly unrelated non-health sites.
So while I think it is sad to see some pharma companies pulling Facebook pages, as I always want to see pharma involved with their customers. I would also like to see pharma put as much effort into studying the rest of the Internet as I have seen them put into Facebook.
It is the rest of the Internet that is screaming for pharma to pay attention. It is the rest of the Internet where pharma can learn what their patients and physician believe and how they choose their actions. It is the rest of the Internet that influences and therefore, matters more.
Monday, August 8, 2011
Another Actos Prediction Comes True & Lawsuits Begin
Back in February of this year we studied the oral diabetes drug, Actos. We had previously studied Avandia and found the starter back in 2004 for the lawsuits that eventually happened in 2008. A friend asked me why Avandia became so damaged while Actos seemed to escape the same fate even though we found that Actos had many concerns from cardiac problems to cancer risks. But the one thing that seemed to not haunt Actos was reported deaths attributed to Actos the way that deaths were attributed to Avandia.
That seems to have changed to today. We predicted that if patients and caregivers started to attribute deaths directly to Actos, that lawsuits would happen almost immediately. Avandia lawsuits took years to happen but the legal community has been looking for an Actos weakness for years. And we predicted that once they found it, the lawsuits would follow fast, furious and in large numbers.
The cancer risk problem that had Actos to be removed from the market in Germany and France in June and caused the FDA to increase warnings, is causing deaths from bladder cancer. Patients and caregivers are directly attributing fatal cancers and death to Actos.
One law firm is reporting that they represent 120 clients and every day that they will add 30 or more a week. Dozens of other firms are advertising for clients.
We see this development as the beginning of the end for Actos. Their combination product of Actos + alogliptin should be at risk as should the use of Actos for other indications such as multiple sclerosis.
If we deepen our prediction as lawsuits begin, we believe that Actos will lose FDA approval by end of the year. And the last TZD falls.
That seems to have changed to today. We predicted that if patients and caregivers started to attribute deaths directly to Actos, that lawsuits would happen almost immediately. Avandia lawsuits took years to happen but the legal community has been looking for an Actos weakness for years. And we predicted that once they found it, the lawsuits would follow fast, furious and in large numbers.
The cancer risk problem that had Actos to be removed from the market in Germany and France in June and caused the FDA to increase warnings, is causing deaths from bladder cancer. Patients and caregivers are directly attributing fatal cancers and death to Actos.
One law firm is reporting that they represent 120 clients and every day that they will add 30 or more a week. Dozens of other firms are advertising for clients.
We see this development as the beginning of the end for Actos. Their combination product of Actos + alogliptin should be at risk as should the use of Actos for other indications such as multiple sclerosis.
If we deepen our prediction as lawsuits begin, we believe that Actos will lose FDA approval by end of the year. And the last TZD falls.
Wednesday, July 27, 2011
Diabetes Medication and Weight Gain
As we continue to study various diabetes medications and patient experiences, I am struck by the number of oral medications that cause weight gain. Patients reported weight gain with 12 of the 18 drugs we studied. And 6 drugs had weight gain incidences of 12.9% (Amaryl) to 31.5% (Actoplus Met). This means that of all of the reports of side effects, weight gain reports comprised 31.5% for Actoplus Met, for example.
Many type 2 patients are trying to lose weight. So the fact that their medication makes that close to impossible and actually has them gaining what could be significant amounts of weight is unacceptable to them.
However, many physicians seem to dismiss patient complaints of weight gain. And today I read an article that sparked this post. I was reviewing information about Takeda releasing new data this week to the FDA on their DPP IV inhibitor, alogliptin. Alogliptin and Actos+alogliptin were originally rejected by FDA because Takeda did not have enough cardiovascular safety data. Takeda is running more studies to specifically look at cardio issues, which is a good thing.
In my research, I found an article from 2010 where researchers favorable to the Actos+alogliptin combo stated that the greater the increase in weight a patient experienced, the greater the decrease in HbA1c. He therefore concluded that the weight gain was purely cosmetic and not a metabolic issue. This was a peer-reviewed article on the NIH website published in Vascular Health Risk Management. In our study, Actos had an incidence of weight gain of 22.5% with some patients report as gaining as much as 50-60 pounds in a manner of a few months.
Significant weight gain has to further stress the already stressed system of a patient with diabetes. More weight has to be a bigger problem that simply cosmetic.
So not only are patients faced with physicians who do not disclose the weigh gain potential of their medications but those evaluating new drugs may not take this side effect seriously. There are several studies that show that even a 5-10% reduction in weight, say 10 to 20 pounds in someone who weight 200, reduces blood glucose levels and reduces the need for medications.
Patients find weight gain caused by diabetes medication to be important and want physicians and researchers to feel the same way.
Many type 2 patients are trying to lose weight. So the fact that their medication makes that close to impossible and actually has them gaining what could be significant amounts of weight is unacceptable to them.
However, many physicians seem to dismiss patient complaints of weight gain. And today I read an article that sparked this post. I was reviewing information about Takeda releasing new data this week to the FDA on their DPP IV inhibitor, alogliptin. Alogliptin and Actos+alogliptin were originally rejected by FDA because Takeda did not have enough cardiovascular safety data. Takeda is running more studies to specifically look at cardio issues, which is a good thing.
In my research, I found an article from 2010 where researchers favorable to the Actos+alogliptin combo stated that the greater the increase in weight a patient experienced, the greater the decrease in HbA1c. He therefore concluded that the weight gain was purely cosmetic and not a metabolic issue. This was a peer-reviewed article on the NIH website published in Vascular Health Risk Management. In our study, Actos had an incidence of weight gain of 22.5% with some patients report as gaining as much as 50-60 pounds in a manner of a few months.
Significant weight gain has to further stress the already stressed system of a patient with diabetes. More weight has to be a bigger problem that simply cosmetic.
So not only are patients faced with physicians who do not disclose the weigh gain potential of their medications but those evaluating new drugs may not take this side effect seriously. There are several studies that show that even a 5-10% reduction in weight, say 10 to 20 pounds in someone who weight 200, reduces blood glucose levels and reduces the need for medications.
Patients find weight gain caused by diabetes medication to be important and want physicians and researchers to feel the same way.
Wednesday, July 20, 2011
AZ & BMS's new diabetes drug, dapagliflozin, not approved by FDA
Two weeks ago, I wrote about AZ & BMS's new diabetes drug, dapaglifizon. Looking at the data, I had my concerns about the drug and its links to cancer, increased infections, and increased renal stress and liver stress.
The drug had it review on July 19. By 9 to 6 votes, the panel rejected the drug over liver and cancer concerns. This was to be the first drug in this new class of SGLT2 inhibitors that removes glucose by moving it through the kidneys and then through urine.
It will be interesting to see what happens with similar drugs from Lilly, J&J, Astellas and Boehringer Ingelheim. Will they have time to ensure they have different data? Can they have different data?
I have to say I was not excited about this new class when I first read about it. I understand it would be once a day dosing and doesn't seem to impede weight loss - these are big positive for patients especially the weight loss.
But the risks of some of the newest classes of drugs are high. And we have just begun to see problems with DPP IV's which I predict will increase.
The FDA may send dapagliflozin back for more trials. But for me, efficacy would have to be tremendous and physicians would have to really screen who gets the drug, for the risks to be worth it.
The drug had it review on July 19. By 9 to 6 votes, the panel rejected the drug over liver and cancer concerns. This was to be the first drug in this new class of SGLT2 inhibitors that removes glucose by moving it through the kidneys and then through urine.
It will be interesting to see what happens with similar drugs from Lilly, J&J, Astellas and Boehringer Ingelheim. Will they have time to ensure they have different data? Can they have different data?
I have to say I was not excited about this new class when I first read about it. I understand it would be once a day dosing and doesn't seem to impede weight loss - these are big positive for patients especially the weight loss.
But the risks of some of the newest classes of drugs are high. And we have just begun to see problems with DPP IV's which I predict will increase.
The FDA may send dapagliflozin back for more trials. But for me, efficacy would have to be tremendous and physicians would have to really screen who gets the drug, for the risks to be worth it.
Tuesday, July 19, 2011
Proactive Product Safety and Efficacy Surveillance Through Observational Research
I just read an article in PharmaVoice on the value of proactive pharmacoviligance . It was dated February 2011; I'm a bit behind on my reading.
However, I couldn't agree more. Manufacturers need to study their products closely post commercialization in order to understand how those products perform once they are used outside of the clinical setting. It is unrealistic to assume that patients and physicians will always have the exact same experiences observed in clinical trials. The world outside of the clinical trial is filled with comordities, concomitant medication, variable adherence, and more. Post-marketing surveillance studies can also serve as a way to catch concerns and address them before they become real issues like lawsuits and loss of approval.
Manufacturers should also want to preserve their products for potential future indications and to ensure that the right patients get the right treatment. I expect executives to would want to know how physician and patient experiences are going to impact the company's bottom line.
Let's face it, all safety and efficacy issues bubble to the surface eventually. We assume that executives would want to proactively manage their portfolios not just because it is good patient care, but because it is good business too.
We spend a good deal of time analyzing patient and physician experiences with pharmaceutical products. We get a real look at how patients and physicians use drugs and devices in real-world settings. We see safety and efficacy issues that definitely can pose potential problems for brands and for companies. We see misunderstandings that offer companies the opportunity to fix things at the source.
When we did our 10-year retrospective study on Avandia, we learned that problems were evident as early as 2004. GSK would have had time to change their label and marketing, instruct physicians, and educate patients. Maybe then in 2008 lawsuits would not have been the recourse patients/caregivers felt that they had to take. Maybe it didn't have to cost GSK so much in legal fees and consumer trust.
When we studied Actos earlier this year, we learned that Takeda faces some real problems with Actos that could impact approvals for future indications. Bladder cancer, bone fractures, and cardiovascular risks are not going away. We believe that Takeda needs to address these risks now for both their current diabetes patients as well as for new trials in different disease states..
So why isn't pharma being more proactive in pharmacoviligance as well as efficacy studies?
We believe that observational research and surveillance studies need to start as soon as a drug or device is in market. It is not only in the best interest of the patient but it is also ultimately in the best interest of the company and the industry. The contributors to the article I read were mostly from non-manufacturers like we are at Wool Labs.
How do we get more of the manufacturers on board?
However, I couldn't agree more. Manufacturers need to study their products closely post commercialization in order to understand how those products perform once they are used outside of the clinical setting. It is unrealistic to assume that patients and physicians will always have the exact same experiences observed in clinical trials. The world outside of the clinical trial is filled with comordities, concomitant medication, variable adherence, and more. Post-marketing surveillance studies can also serve as a way to catch concerns and address them before they become real issues like lawsuits and loss of approval.
Manufacturers should also want to preserve their products for potential future indications and to ensure that the right patients get the right treatment. I expect executives to would want to know how physician and patient experiences are going to impact the company's bottom line.
Let's face it, all safety and efficacy issues bubble to the surface eventually. We assume that executives would want to proactively manage their portfolios not just because it is good patient care, but because it is good business too.
We spend a good deal of time analyzing patient and physician experiences with pharmaceutical products. We get a real look at how patients and physicians use drugs and devices in real-world settings. We see safety and efficacy issues that definitely can pose potential problems for brands and for companies. We see misunderstandings that offer companies the opportunity to fix things at the source.
When we did our 10-year retrospective study on Avandia, we learned that problems were evident as early as 2004. GSK would have had time to change their label and marketing, instruct physicians, and educate patients. Maybe then in 2008 lawsuits would not have been the recourse patients/caregivers felt that they had to take. Maybe it didn't have to cost GSK so much in legal fees and consumer trust.
When we studied Actos earlier this year, we learned that Takeda faces some real problems with Actos that could impact approvals for future indications. Bladder cancer, bone fractures, and cardiovascular risks are not going away. We believe that Takeda needs to address these risks now for both their current diabetes patients as well as for new trials in different disease states..
So why isn't pharma being more proactive in pharmacoviligance as well as efficacy studies?
We believe that observational research and surveillance studies need to start as soon as a drug or device is in market. It is not only in the best interest of the patient but it is also ultimately in the best interest of the company and the industry. The contributors to the article I read were mostly from non-manufacturers like we are at Wool Labs.
How do we get more of the manufacturers on board?
Monday, July 18, 2011
Too Many Diabetes Drugs Simultaneously and Drug Interactions
I have been working on the analysis of a new study we just completed focused on 18 oral diabetes medications.
Part of the analysis is looking at the medications that patients are taking and the potential impact on the performance of their diabetes drugs.
First, I am struck by the fact that many patients are on many drugs simultaneously. It seems that if one drug is not working, then they are prescribed another to add on top without any analysis of why that initial drug didn't produce the desired results. Yes, some patients are on a more obviously structured approach of shorter-acting combined with longer-acting products. Others, though, seem to have the kitchen sink thrown at them. This approach seems unique to diabetes type II. I can't say that I see this in anyother disease state; even cancer with its cocktails and combination therapy is quite disciplined.
Ok, so what are we seeing. First, patients get prescribed a drug at diagnosis, not uncommonly, Metformin. So patients' initial physical response is supposed to be (1) reduction in blood glucose, (2) reduction in hA1c, and/or (3) side effects or not. If the patient's numbers don't improve, I typically don't see evidence that the patient and the physician sit together and ask why. (We'll skip the fact that physicians tend to ignore patient complaints of side effects with Metformin and therefore, patients are not taking the drug as prescribed in many, many cases - which would be why).
What we do see is that patients will be prescribed another drug to put on top of Metformin, not always switched, just added to. And sometimes that happens again and again. Drugs don't always get removed from the regimen, just added to. And dosing schedules get complicated.
Each time a drug is added, several things can happen. First complicated regimens are hard for patients to keep up with. Second, these drugs can have interactions both with each other and with other non-diabetes drugs. Some diabetes drugs interfere with one another creating hypoglycemia and/or unstabled blood glucose numbers, which is maddening for patients who can't seem to get their numbers under control. Next, physicians see the lack of control and more often than not, blame the patient without always scrutinizing the whole process.
At some point, sometimes quite confusingly for patients, the drugs all get swamped out for a new set. Sometimes patients just start on one new drug. But the pattern starts again of adding but not subtracting until the next critical mass happens.
The pattern doesn't necessarily change if the patient starts on insulin. At first, insulin seemsused alone but that doesn't always last and oral meds are added back.
At the same time, patients are working changing their diet and exercise patterns, which also impacts drug performance at the original dosing regimen many times resulting in hypoglycemia. And with patients on multiple drugs at one time, the non-diabetes drug interactions grow - birth control and blood pressure meds, NSAIDS, thyroid drugs, some antibiotics, asthma meds - all increase risk for both hypoglycemia and hyperglycemia simultaneously. No wonder so many people can't get their numbers under control.
The whole process doesn't seem the best way to tackle what is called an epidemic. Many patients do figure it out with hard work and lots of research. But a lot more don't.
So more drugs on the market is not going to make this better. Diabetes needs a better approach that figures out why some medications work and others don't, how diet and exercise really impact medication needs, and how to reliably stop the advance of the disease. The kitchen sink approach is not a long-term strategy.
Part of the analysis is looking at the medications that patients are taking and the potential impact on the performance of their diabetes drugs.
First, I am struck by the fact that many patients are on many drugs simultaneously. It seems that if one drug is not working, then they are prescribed another to add on top without any analysis of why that initial drug didn't produce the desired results. Yes, some patients are on a more obviously structured approach of shorter-acting combined with longer-acting products. Others, though, seem to have the kitchen sink thrown at them. This approach seems unique to diabetes type II. I can't say that I see this in anyother disease state; even cancer with its cocktails and combination therapy is quite disciplined.
Ok, so what are we seeing. First, patients get prescribed a drug at diagnosis, not uncommonly, Metformin. So patients' initial physical response is supposed to be (1) reduction in blood glucose, (2) reduction in hA1c, and/or (3) side effects or not. If the patient's numbers don't improve, I typically don't see evidence that the patient and the physician sit together and ask why. (We'll skip the fact that physicians tend to ignore patient complaints of side effects with Metformin and therefore, patients are not taking the drug as prescribed in many, many cases - which would be why).
What we do see is that patients will be prescribed another drug to put on top of Metformin, not always switched, just added to. And sometimes that happens again and again. Drugs don't always get removed from the regimen, just added to. And dosing schedules get complicated.
Each time a drug is added, several things can happen. First complicated regimens are hard for patients to keep up with. Second, these drugs can have interactions both with each other and with other non-diabetes drugs. Some diabetes drugs interfere with one another creating hypoglycemia and/or unstabled blood glucose numbers, which is maddening for patients who can't seem to get their numbers under control. Next, physicians see the lack of control and more often than not, blame the patient without always scrutinizing the whole process.
At some point, sometimes quite confusingly for patients, the drugs all get swamped out for a new set. Sometimes patients just start on one new drug. But the pattern starts again of adding but not subtracting until the next critical mass happens.
The pattern doesn't necessarily change if the patient starts on insulin. At first, insulin seemsused alone but that doesn't always last and oral meds are added back.
At the same time, patients are working changing their diet and exercise patterns, which also impacts drug performance at the original dosing regimen many times resulting in hypoglycemia. And with patients on multiple drugs at one time, the non-diabetes drug interactions grow - birth control and blood pressure meds, NSAIDS, thyroid drugs, some antibiotics, asthma meds - all increase risk for both hypoglycemia and hyperglycemia simultaneously. No wonder so many people can't get their numbers under control.
The whole process doesn't seem the best way to tackle what is called an epidemic. Many patients do figure it out with hard work and lots of research. But a lot more don't.
So more drugs on the market is not going to make this better. Diabetes needs a better approach that figures out why some medications work and others don't, how diet and exercise really impact medication needs, and how to reliably stop the advance of the disease. The kitchen sink approach is not a long-term strategy.
Friday, July 8, 2011
Our predictions for Actos are coming true and the future of the drug is at risk.
With the demise of Avandia, Actos is now the world's leading type II diabetes medication.
However, Actos has lost support just recently in France and Germany over bladder cancer concerns.
And new information on macular edema concerns add more risks. The US has increased warnings but has not moved to rescind approval.
In our March 2011 report, we made a few predictions about the future of Actos. The first prediction was that increased risk for bladder cancer, macular edema, bone fractures, and heart risks for younger patients would surface and cause problems for the brand, including its removal from the market. The removal has started in the EU.
The second prediction was that any further movement to restrict or rescrind support for Avandia would also cause problems for Actos since we do not believe the brand is strong enough to be the last TZD standing. The FDA is removing Avandia from US retail availability in November of this year. Therefore, we see even more increased scrutiny of Actos as the brand had never really been able to separate itself completely from comparisons to Avandia.
Now Actos goes off patent at the end of this year but Takeda needs Actos to survive well past patent expiration. Takeda has Actos in clinical trials for future indications including MS. So, if the product gets pulled completely, it will not be able to expand.
But patients with MS as well as other autoimmune diseases that Takeda is eyeing for Actos are at risk for bone fractures. So our third prediction is that if increases in bone fractures surface in enough numbers to catch the FDA's attention, it could end future trials and indications. Also MS patients are younger (the average age of diagnosis is 33). We may seen increases in heart-related problems in MS trials with Actos further complicating things.
Actos is a huge part of the Takeda portfolio and revenue. It's future seems at risk and those risks have accumulated quickly in the last 6 months or so. So does Actos in jeopardy mean Takeda is in jeopardy too?
However, Actos has lost support just recently in France and Germany over bladder cancer concerns.
And new information on macular edema concerns add more risks. The US has increased warnings but has not moved to rescind approval.
In our March 2011 report, we made a few predictions about the future of Actos. The first prediction was that increased risk for bladder cancer, macular edema, bone fractures, and heart risks for younger patients would surface and cause problems for the brand, including its removal from the market. The removal has started in the EU.
The second prediction was that any further movement to restrict or rescrind support for Avandia would also cause problems for Actos since we do not believe the brand is strong enough to be the last TZD standing. The FDA is removing Avandia from US retail availability in November of this year. Therefore, we see even more increased scrutiny of Actos as the brand had never really been able to separate itself completely from comparisons to Avandia.
Now Actos goes off patent at the end of this year but Takeda needs Actos to survive well past patent expiration. Takeda has Actos in clinical trials for future indications including MS. So, if the product gets pulled completely, it will not be able to expand.
But patients with MS as well as other autoimmune diseases that Takeda is eyeing for Actos are at risk for bone fractures. So our third prediction is that if increases in bone fractures surface in enough numbers to catch the FDA's attention, it could end future trials and indications. Also MS patients are younger (the average age of diagnosis is 33). We may seen increases in heart-related problems in MS trials with Actos further complicating things.
Actos is a huge part of the Takeda portfolio and revenue. It's future seems at risk and those risks have accumulated quickly in the last 6 months or so. So does Actos in jeopardy mean Takeda is in jeopardy too?
Tuesday, July 5, 2011
Why are there differences in FDA and EU regulatory viewpoints?
Last week the FDA reviewed and rescinded support for Avastin for breast cancer. At the same time, the EU regulators expanded support by approving Avastin's use first line with the chemotherapy agent Xeloda. Interestingly, there are quite few US patients on this same combination who report success.
In June of this year, France and Germany rescinded support for Actos and the EU version of Actoplus Met based on the reports of increased risk for bladder cancer. The US regulators added a warning for increased risk for bladder cancer for those taking Actos, Actoplus Met and Duetact for more than 1 year. But the FDA has not moved to rescind support of Actos or its combos here in the US, yet. That might change now that the ADA reported in San Diego last week that Actos and Avandia both show an increased occurance of macular edema.
And the EU pulled Avandia while the FDA restricted its use but did not ban it.
J&J's blood thinner Xarelto just won FDA approval in a pretty long battle while the drug has been used in the EU since 2008.
There are plenty more differences in both biologics and devices. In our data, we see patients experiencing the same benefits and concerns regardless of geography. Patients stories paint a more global viewpoint than it seems the regulators do and are typically confused as to why a drug is banned on one continent but available in another.
I certainly want the FDA to take its time and use solid data when they approve or ban products but it seems that perhaps data, experiences, and criteria could be shared more across regulatory bodies. The manufacturers are global as are patient experiences.
So, why do these regulators differ.
In June of this year, France and Germany rescinded support for Actos and the EU version of Actoplus Met based on the reports of increased risk for bladder cancer. The US regulators added a warning for increased risk for bladder cancer for those taking Actos, Actoplus Met and Duetact for more than 1 year. But the FDA has not moved to rescind support of Actos or its combos here in the US, yet. That might change now that the ADA reported in San Diego last week that Actos and Avandia both show an increased occurance of macular edema.
And the EU pulled Avandia while the FDA restricted its use but did not ban it.
J&J's blood thinner Xarelto just won FDA approval in a pretty long battle while the drug has been used in the EU since 2008.
There are plenty more differences in both biologics and devices. In our data, we see patients experiencing the same benefits and concerns regardless of geography. Patients stories paint a more global viewpoint than it seems the regulators do and are typically confused as to why a drug is banned on one continent but available in another.
I certainly want the FDA to take its time and use solid data when they approve or ban products but it seems that perhaps data, experiences, and criteria could be shared more across regulatory bodies. The manufacturers are global as are patient experiences.
So, why do these regulators differ.
Friday, July 1, 2011
Is the new diabetes drug Dapagliflozon safe and effective?
On June 24, 2011, Bloomberg reports that the BMS and AZ diabetes drug, dapagliflozon, is safe and effective based on a study comparing the drug with metformin against metformin+glipizide. The article did acknowledge that dapagliflozon was associated with more urinary and genital infections.
On June 27, 2011, Yahoo health reports that dapagliflozon is effective but in addition to patients having more infections, it seems that an increase in bladder and breast cancer may also be associated with the drug.
Dapagliflozon is in a new class of drugs that blocks glucose from being absorbed into the bloodstream through the kidneys and allowing more sugar to be released in the urine. Therefore, sugar spends more time in the urinary tract, which could explain the increases in infections as bacteria would have more time to grow. Diabetes patients are already at increased risks for these types of infections so this drug increases that risk even more.
However, cancer increases should be met with some concern. Actos is also being linked to increases in bladder cancer by those who take it more than a year. Januvia and other DPP-IV drugs are linked to suppressing the body's able to fight cancer. As most patients diagnosed with diabetes remain on some medication for perhaps the rest of their lives, the increased cancer risks are serious.
And the label will already carry the risk for renal impairment or failure which would make sense as the kidneys would have to work harder on this drug.
That is not to say that the drug doesn't do some good things. It can lower blood pressure and seems to help patients make it easier to lose weight. Patients only need to take it once a day. These are real positives.
Lilly, J&J, Boehringer Ingelheim, and Astellas are all developing drugs in this new class. So, the risk-benefit profile needs to be carefully watched. If in a two year study the cancer and infection rates are already significant, what happens after 10 years.
The Bloomberg article reports that physicians will begin using the drug immediately upon approval. The FDA is scheduled their review for July 19.
If I were a patient and I looked at this data, I'm not sure I would be ready to take it so fast.
It is rare in the data we have (and we have an enormouse amount of diabetes data), do I see phyicians and patients talking about that patient's personal risks before taking a drug. So for example, for dapagliflozon, I would think it wise to find out if the patient already had frequent URI or genital infections, compromised kidneys and/or if there is a family history of certain cancers. To me, immediately if any of these things were true, then the patient would not be a candidate for this drug or any in its class. That way, perhaps this drug can be useful and valuable while mitigating the risks in the wrong patients.
However, since we do not see this happening much today, I am not convinced it will happen with this drug either. Therefore, my prediction is that is the FDA approves the drug, we will see serious problems reported by patients within 2 or 3 years post approval that perhaps could have been avoided.
On June 27, 2011, Yahoo health reports that dapagliflozon is effective but in addition to patients having more infections, it seems that an increase in bladder and breast cancer may also be associated with the drug.
Dapagliflozon is in a new class of drugs that blocks glucose from being absorbed into the bloodstream through the kidneys and allowing more sugar to be released in the urine. Therefore, sugar spends more time in the urinary tract, which could explain the increases in infections as bacteria would have more time to grow. Diabetes patients are already at increased risks for these types of infections so this drug increases that risk even more.
However, cancer increases should be met with some concern. Actos is also being linked to increases in bladder cancer by those who take it more than a year. Januvia and other DPP-IV drugs are linked to suppressing the body's able to fight cancer. As most patients diagnosed with diabetes remain on some medication for perhaps the rest of their lives, the increased cancer risks are serious.
And the label will already carry the risk for renal impairment or failure which would make sense as the kidneys would have to work harder on this drug.
That is not to say that the drug doesn't do some good things. It can lower blood pressure and seems to help patients make it easier to lose weight. Patients only need to take it once a day. These are real positives.
Lilly, J&J, Boehringer Ingelheim, and Astellas are all developing drugs in this new class. So, the risk-benefit profile needs to be carefully watched. If in a two year study the cancer and infection rates are already significant, what happens after 10 years.
The Bloomberg article reports that physicians will begin using the drug immediately upon approval. The FDA is scheduled their review for July 19.
If I were a patient and I looked at this data, I'm not sure I would be ready to take it so fast.
It is rare in the data we have (and we have an enormouse amount of diabetes data), do I see phyicians and patients talking about that patient's personal risks before taking a drug. So for example, for dapagliflozon, I would think it wise to find out if the patient already had frequent URI or genital infections, compromised kidneys and/or if there is a family history of certain cancers. To me, immediately if any of these things were true, then the patient would not be a candidate for this drug or any in its class. That way, perhaps this drug can be useful and valuable while mitigating the risks in the wrong patients.
However, since we do not see this happening much today, I am not convinced it will happen with this drug either. Therefore, my prediction is that is the FDA approves the drug, we will see serious problems reported by patients within 2 or 3 years post approval that perhaps could have been avoided.
Thursday, June 30, 2011
Patients, consumers, and physicians comment on Avastin and FDA decision to rescind approval
As patients, consumers and physicians react to the FDA panel decision yesterday on Avastin, several themes are emerging.
Many are wondering what happens now to the 17,500 patients currently on Avastin. Others wonder why these women respond well, what is different about them and why no one knows how to define them as a subpopulation to target Avastin to the "right" patients. Some feel that since the disease is cancer and not "growing new eye lashes" that if Avastin works for some part of the population, it should be approved simply because it is cancer. Some feel that the idea that Avastin is too risky is a bit absurb given that Stage IV breast cancer patients would be more likely to die of cancer than drug side effects.
Some physicians are adamant that they do not use Avastin if it doesn't work, so cost shouldn't be an issue and the drug should be approved so that physicians and patients can work out whether Avastin is the right option. Now cost, is not supposed to be part of this equation, but it is hard to imagine it not occuring to anyone as Avastin is one of the most expensive drugs ever.
The FDA's decision is not without support. Some feel that a drug that consistently shows negative data should not be approved. Others feel that patients' stories are anectodal and should not sway the FDA's decision.
While it is rare for the FDA to even consider an appeal, I am not sure that these hearings where helpful to anyone. No one's opinion has changed. No one learned anything new. Patients were allowed to plead but Genentech did not support them with any new clinical data. Genentech also did not use the 7 months between December and now to have a hypothesis on why these women are able to benefit to give the FDA a reason to allow them to test that hypothesis and keep Avastin available.
The FDA is supposed to evaluate Avastin based on science. And many people feel that emotional appeals have no place in science.
But patient experiences are data points and are science. Patient experiences are what clinical trials are evaluated on and how drugs get approved. The FDA relies on patient experiences to review adverse events. Post-marketing studies are done to gather patient experiences.
The delivery of patient data over the last two days was heart-breaking and unnecessary because I think all anyone will remember is the emotional horror that patients and caregivers put themselves through and will miss the "data" part of the equation.
There are 17,500 data points that represent the basis for the science that needs to occur if we are going to understand Avastin. If someone was able to present the science of those 17,500 patients without any emotional pleas from the audience, perhaps that would have been a more productive and insightful hearing.
Many are wondering what happens now to the 17,500 patients currently on Avastin. Others wonder why these women respond well, what is different about them and why no one knows how to define them as a subpopulation to target Avastin to the "right" patients. Some feel that since the disease is cancer and not "growing new eye lashes" that if Avastin works for some part of the population, it should be approved simply because it is cancer. Some feel that the idea that Avastin is too risky is a bit absurb given that Stage IV breast cancer patients would be more likely to die of cancer than drug side effects.
Some physicians are adamant that they do not use Avastin if it doesn't work, so cost shouldn't be an issue and the drug should be approved so that physicians and patients can work out whether Avastin is the right option. Now cost, is not supposed to be part of this equation, but it is hard to imagine it not occuring to anyone as Avastin is one of the most expensive drugs ever.
The FDA's decision is not without support. Some feel that a drug that consistently shows negative data should not be approved. Others feel that patients' stories are anectodal and should not sway the FDA's decision.
While it is rare for the FDA to even consider an appeal, I am not sure that these hearings where helpful to anyone. No one's opinion has changed. No one learned anything new. Patients were allowed to plead but Genentech did not support them with any new clinical data. Genentech also did not use the 7 months between December and now to have a hypothesis on why these women are able to benefit to give the FDA a reason to allow them to test that hypothesis and keep Avastin available.
The FDA is supposed to evaluate Avastin based on science. And many people feel that emotional appeals have no place in science.
But patient experiences are data points and are science. Patient experiences are what clinical trials are evaluated on and how drugs get approved. The FDA relies on patient experiences to review adverse events. Post-marketing studies are done to gather patient experiences.
The delivery of patient data over the last two days was heart-breaking and unnecessary because I think all anyone will remember is the emotional horror that patients and caregivers put themselves through and will miss the "data" part of the equation.
There are 17,500 data points that represent the basis for the science that needs to occur if we are going to understand Avastin. If someone was able to present the science of those 17,500 patients without any emotional pleas from the audience, perhaps that would have been a more productive and insightful hearing.
Wednesday, June 29, 2011
FDA panel recommends rescinding Avastin approval for breast cancer
Today the FDA panel recommends rescinding Avastin support for breast cancer. The FDA doesn't need to follow the panels recommendation but typically does. We will follow patient and caregiver responses over the next few days,
Medtronic's Infuse Bone Graft in trouble for research not reporting AEs
Medtronic is being scrutinized by the FDA for failing to report serious adverse events found during clinical studies of their Infuse bone graft product. Papers written by physicians and researchers based on the clinical work are alleged to have downplayed the seriousness of certain problems such as painful bone overgrowth or didn't attribute the problems to the Infuse product. This is an important issue for many reasons but mostly (IMHO) because surgeons and patients base their decisions on the procedures to use based on these research papers.
These are situations where we believe that studying patient experience data can help identify problems with products that are missed, misreported or even just unexpected.
As far as the Infuse bone graft, patient experiences would have identified problems sooner. In fact, the are patient reports of pain, overgrowth, throat swelling, difficulty breathing, and repeat surgeries that patients attribute to Infuse as far back as 2003. And their stories continue through today.
The type of technology we use to study patients experiences surrounding product safety and efficacy did not exist until 2008. However now we believe that there is no reason for companies not to study real-world and large-scale patient experiences to see how their products are performing. Not only is this the responsible thing to do for patients, it really is a way for the industry to protect its business. Medtronic has been embroiled in lawsuits over Infuse since 2008. It looks like the lawsuits will continue and will cost them millions. It's a shame because perhaps if Medtronic knew more about what patients knew, they might have been able to avoid lawsuits as well as what could result in the FDA rescinding of approval of Infuse. In March 2011, the FDA failed to approve Amplify, their latest bone graft product, without more data. So the stakes are high.
As I post this, the CEO of Medtronic is trying to diffuse the problem in the media. If Medtronic had been more in tune with patient experiences, maybe he wouldn't have to be doing that right now.
In the long run, not knowing what problems exist, how widespread they are, and how patients feel about them doesn't seem a wise business move. And it isn't good patient care.
These are situations where we believe that studying patient experience data can help identify problems with products that are missed, misreported or even just unexpected.
As far as the Infuse bone graft, patient experiences would have identified problems sooner. In fact, the are patient reports of pain, overgrowth, throat swelling, difficulty breathing, and repeat surgeries that patients attribute to Infuse as far back as 2003. And their stories continue through today.
The type of technology we use to study patients experiences surrounding product safety and efficacy did not exist until 2008. However now we believe that there is no reason for companies not to study real-world and large-scale patient experiences to see how their products are performing. Not only is this the responsible thing to do for patients, it really is a way for the industry to protect its business. Medtronic has been embroiled in lawsuits over Infuse since 2008. It looks like the lawsuits will continue and will cost them millions. It's a shame because perhaps if Medtronic knew more about what patients knew, they might have been able to avoid lawsuits as well as what could result in the FDA rescinding of approval of Infuse. In March 2011, the FDA failed to approve Amplify, their latest bone graft product, without more data. So the stakes are high.
As I post this, the CEO of Medtronic is trying to diffuse the problem in the media. If Medtronic had been more in tune with patient experiences, maybe he wouldn't have to be doing that right now.
In the long run, not knowing what problems exist, how widespread they are, and how patients feel about them doesn't seem a wise business move. And it isn't good patient care.
Some Data from our December 2010 Avastin & Breast Cancer Study
As the FDA ponders Avastin's future, I went back to our December 2010 Breast Cancer study to look at some Avastin results.
We had analyzed close to 2,000 conversations just on Avastin. Overall sentiment for Avastin was positive meaning that there were more conversations in support of Avastin than not.
I can sum up the overall view of Avastin in one sentence; "Avastin is one piece of the puzzle for me" as one patient stated. Conversations included patients, caregivers, nurses, and physicians. All were able to provide stories of patient success. Nurses recount stories of how many patients they did see respond well to Avastin. Patients attributed their long remissions to Avastin. Caregivers felt that their loved ones were either still alive or had more time because of Avastin. And physicians felt that chemotherapy worked better when Avastin was added.
Unfortunately, it seems that physicians and nurse were not able to predict which patients would respond well. And obviously Avastin does not work for everyone.
As we all know, patients and caregivers were outraged when the FDA rescinded its support of Avastin for breast cancer. They still are. They believe that the FDA is choosing death for them. Their anger and fear are powerfully spoken and it is very hard not to be affected. Even many patients that did not respond to Avastin do not want to see the drug unsupported as they feel that all patients should get a chance to see if Avastin works for them.
There are consumers and professionals who look at the clinical data and their own experiences and have come to the conclusion that Avastin is not effective in the treatment of breast cancer. And while there are some patients who feel that Avastin should not keep its approval, breast cancer patients and caregivers are less likely to want to see approval reversed than others.
While the FDA may make their decision on overall collective survival data, patients and caregivers feel strongly that their experience data is important and should be taken into consideration.
We had analyzed close to 2,000 conversations just on Avastin. Overall sentiment for Avastin was positive meaning that there were more conversations in support of Avastin than not.
I can sum up the overall view of Avastin in one sentence; "Avastin is one piece of the puzzle for me" as one patient stated. Conversations included patients, caregivers, nurses, and physicians. All were able to provide stories of patient success. Nurses recount stories of how many patients they did see respond well to Avastin. Patients attributed their long remissions to Avastin. Caregivers felt that their loved ones were either still alive or had more time because of Avastin. And physicians felt that chemotherapy worked better when Avastin was added.
Unfortunately, it seems that physicians and nurse were not able to predict which patients would respond well. And obviously Avastin does not work for everyone.
As we all know, patients and caregivers were outraged when the FDA rescinded its support of Avastin for breast cancer. They still are. They believe that the FDA is choosing death for them. Their anger and fear are powerfully spoken and it is very hard not to be affected. Even many patients that did not respond to Avastin do not want to see the drug unsupported as they feel that all patients should get a chance to see if Avastin works for them.
There are consumers and professionals who look at the clinical data and their own experiences and have come to the conclusion that Avastin is not effective in the treatment of breast cancer. And while there are some patients who feel that Avastin should not keep its approval, breast cancer patients and caregivers are less likely to want to see approval reversed than others.
While the FDA may make their decision on overall collective survival data, patients and caregivers feel strongly that their experience data is important and should be taken into consideration.
Monday, June 27, 2011
Avastin faces the FDA again on breast cancer
This week Avastin faces the FDA again. The agency ruled last year that Avastin does not increase overall survival or progession-free survival for women with breast cancer. But Roche/Genentech has come back to the FDA to challenge that decision. Analysts are not optimistic that the brand will survive with any breast cancer label but it is rare for the FDA to grant an appeal. So I would expect that many are interested in the results.
According to advocacy groups, there are 17,000 women on Avastin for advanced breast cancer. Our studies have shown that there are those who are convinced that Avastin has increased PFS. When the FDA repealed its support, many patients were extremely angry and the accused the agency of creating death panels. Their stories were difficult to read. And there are oncologists who believe that Avastin did/does work for certain patients.
Avastin is expensive at about $8,000/month so if the current ruling stands, it is likely most patients will not be able to continue on the drug as insurance coverage will be gone.
Genentech is willing to conduct more targeted studies to determine who is the best candidate for the drug and the FDA is open to more research. More data may pinpoint why some patients respond and others do not. While OS is the gold standard, PFS matters to patients and their families.
So on Tuesday and Wednesday of this week, 17,000 patients, their families and their medical teams will be holding their breadth.
According to advocacy groups, there are 17,000 women on Avastin for advanced breast cancer. Our studies have shown that there are those who are convinced that Avastin has increased PFS. When the FDA repealed its support, many patients were extremely angry and the accused the agency of creating death panels. Their stories were difficult to read. And there are oncologists who believe that Avastin did/does work for certain patients.
Avastin is expensive at about $8,000/month so if the current ruling stands, it is likely most patients will not be able to continue on the drug as insurance coverage will be gone.
Genentech is willing to conduct more targeted studies to determine who is the best candidate for the drug and the FDA is open to more research. More data may pinpoint why some patients respond and others do not. While OS is the gold standard, PFS matters to patients and their families.
So on Tuesday and Wednesday of this week, 17,000 patients, their families and their medical teams will be holding their breadth.
Thursday, June 23, 2011
Weight Loss Surgery Good for Diabetes Type II
Today, a report published in the Archives of Surgery stated that 8 out of 10 obese patients were cured of diabetes after weight loss surgery. The researchers went through the data of nine different studies of patients with diabetes who has some sort of weight loss surgery.
We reported back in February of this year based on our 10 year study that weight loss surgery was able to put type II diabetes into remission for a majority of patients even before they left the operating table. We also predicted that the FDA would lower the BMI requirements for coverage from 35 and higher to 30 - 35, which they did the following month for Lap-Band surgery.
Our last prediction in that report was that surgery type mattered and that gastric bypass was more effective than other surgeries and it appears that also is true as the researchers of the aforementioned report also found that gastric bypass has a much better cure rate.
Our data also showed that bariatric surgery eliminated hypertension in a majority of patients. And this week, an advanced release of a peer-reviewed article in Surgery for Obesity and Related Diseases states that gastric bypass significantly reduced the inflammation associated with cancer and diabetes. Their study is part of a bigger series that is intended to show that gastric bypass surgery helps the body fight high-risk diseases. Our data also supports that hypothesis.
We reported back in February of this year based on our 10 year study that weight loss surgery was able to put type II diabetes into remission for a majority of patients even before they left the operating table. We also predicted that the FDA would lower the BMI requirements for coverage from 35 and higher to 30 - 35, which they did the following month for Lap-Band surgery.
Our last prediction in that report was that surgery type mattered and that gastric bypass was more effective than other surgeries and it appears that also is true as the researchers of the aforementioned report also found that gastric bypass has a much better cure rate.
Our data also showed that bariatric surgery eliminated hypertension in a majority of patients. And this week, an advanced release of a peer-reviewed article in Surgery for Obesity and Related Diseases states that gastric bypass significantly reduced the inflammation associated with cancer and diabetes. Their study is part of a bigger series that is intended to show that gastric bypass surgery helps the body fight high-risk diseases. Our data also supports that hypothesis.
In fact, our data showed that even though some patients gained all of their weight back, their type II diabetes did not necessarily return.
Of course, gastric bypass surgery is expensive and not without risk, some quite serious. But the cost of surgery is one-time (assuming that there are no complications). And even at $20,000 - $25,000 per surgery, it should be cost effective given the elimination of the life-long need for expensive medication and supplies as well as the savings from a decrease in diabetes-related complications.
In 2008, a University of Quebec at Montreal study that showed that insurance companies recouped the cost of surgery in 2-4 years. As reported by Reuters today, Dr. Jon Gould of the University of Wisconsin and head of their weight loss surgery program stated that costs can be recouped in 18 months to 2 years.
So why isn't this surgery used more? In some cases, insurance has not caught up with science and some patients might not be ready for the risk. But why else?
Given all of the work we have done in diabetes, I personally do not think diabetes type II is a manageable disease. At least, not the way it is managed today. The current methods of diabetes management seem unsustainable - drugs are expensive with a myriad of side effects, even reasonably compliant patients find that their drugs stop working over time, and physicians seem at a loss of what to do with their patients.
In the US alone, there are 18 million people in the US diagnosed with diabetes and many would qualify for this surgery. And the data shows and has shown for at least 10 years, that weight loss surgery is an effective tool.
Time to rethink diabetes.
Supreme Court rejects generic drug labeling suits
Today the Supreme Court ruled that generic manufacturers cannot be sued because they did not provide adequate labeling warning about side effects. This means that the generic drug does have to warn patients about side effects on its label when the branded drug doesn't.
The generic drug manufacturers argued that US law requires them to have the same label as the brand-name equivalent.
I have mixed feelings about this. I am not a big fan of the constant law suits we see, but at the same time I think that generic drug manufacturers have their own responsibilities for their products beyond the responsibilities of the branded drug maker.
For one thing, generic drugs are not necessarily identical to their branded equivalent. They are very close but not exactly the same. Generics are made by different manufacturers using different processes and sometimes the active ingredient strength is slightly different. We also see enough data where patients say that generics perform differently than brand-named drugs. So the generic could be slightly different and it could cause its own side effect. To unilaterally say that is not possible, doesn't seem completely thought-through IMHO.
Also, generics are usually on the market after a branded drug goes off patent and for a long time afterwards. So they may end up getting used longer. And as more drugs go generic, more information could surface about the generic drug before it surfaces about the branded drug.
So I am definitely leaning toward this not being a good idea. I see this issue resurfacing and unfortunately, not under the best circumstances.
The generic drug manufacturers argued that US law requires them to have the same label as the brand-name equivalent.
I have mixed feelings about this. I am not a big fan of the constant law suits we see, but at the same time I think that generic drug manufacturers have their own responsibilities for their products beyond the responsibilities of the branded drug maker.
For one thing, generic drugs are not necessarily identical to their branded equivalent. They are very close but not exactly the same. Generics are made by different manufacturers using different processes and sometimes the active ingredient strength is slightly different. We also see enough data where patients say that generics perform differently than brand-named drugs. So the generic could be slightly different and it could cause its own side effect. To unilaterally say that is not possible, doesn't seem completely thought-through IMHO.
Also, generics are usually on the market after a branded drug goes off patent and for a long time afterwards. So they may end up getting used longer. And as more drugs go generic, more information could surface about the generic drug before it surfaces about the branded drug.
So I am definitely leaning toward this not being a good idea. I see this issue resurfacing and unfortunately, not under the best circumstances.
Thursday, June 16, 2011
Introduction to the Evolution of Post Marketing Surveillance
The current method of reporting adverse events (AEs) is based on manufacturer, clinical trial sponsor and investigator, physician, and even patient reports to the FDA. We all know that the agency is interested in “serious, unexpected, suspected adverse reactions”, as defined by their standards.
However, based on what is published from many sources, the current methods are not 100% satisfactory. The FDA still gets dinged by the OIG and consumers still complain. Lawsuits happen.
In May of 2008, the FDA launched the Sentinel Initiative. On their website, the agency describes the initiative as follows:
“The Sentinel Initiative aims to develop and implement a proactive system that will complement existing systems that the Agency has in place to track reports of adverse events linked to the use of its regulated products.”
A few years ago, I was able to look into the methods that the FDA was proposing to include in the initiative and the new data sources included medical and claims records and prescribing data. I agree that these data sources will be valuable in the overall long-term post-marketing evaluation of products.
However, I was struck by something else. We know based on our work in Internet conversation analysis and years of healthcare marketing that patients take quite awhile to go from healthcare complaint or issue to actually going to the doctor. I have seen patients take up to a year to go to the doctor for a problem so we can assume that it would be weeks at best before a patient sees their doctor about a perceived problem. And we know that it takes at least 2 months for data from a medical visit to get from the physician to claims data to someone to analyze the claims data. So the time from complaint to usable data will be at least 3 months.
A lot can happen in 3 months. No doubt that the Sentinel Initiative is a needed project. However, I see it akin to trying to identify patient zero in an epidemic – an extremely important task for containment and treatment but sometimes one that just lets us watch a terrible problem spread around the world.
At the same time, over the last 10 years the Internet has become a central part of how patients manage their diseases and conditions. Patients actively discuss how they feel their medication is performing based on their own experiences. And in many cases, patients are aware of clinical standards and are sophisticated in their evaluation of product performance because of their extensive personal research and interaction with other patients.
So I thought, what if we could offer an additional method for measuring safety and also efficacy based on this real-world experience? Yes, there are Phase IV/V studies but today, they are accomplished in the current clinical trial format that is still not really “real world”. I understand why trials are done the way they are; I have been a researcher. However, many researchers also agree that the study format makes it hard to really see what will happen when a drug is released into the “wild” without the supervision of inclusion and exclusion criteria and strictly monitored adherence regimens.
Wool Labs is working to develop Phase IV/V programs to look at safety and efficacy of products through the lens of how patients report performance and experience. We already work with clients as well as publish our own research on how patients discuss their diseases and conditions, medication, and safety and efficacy measures.
So the point to this blog is to explore this concept further. We are working today to define our first such study with a major university (more as time unfolds). But I want to discuss how what we already see today and the protocols needed in the future. I am interested in advancing the debate of using different and more “real world” methods for evaluating the performance of products that still can be scientifically rigorous but offer earlier signals and insights into the future.
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