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.

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.

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.

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.

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.

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.

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.