Monday, October 20, 2014

Upcoming 11/3/2014 FDA-DOC Meeting; Concerns About FDA Biosimilar Guidance(s)

At this point, I don't think its really necessary for me to repeat too much of the content that is already circulating within the diabetes online community of blogs about the forthcoming Monday, November 3, 2014 meeting  from 1:00 pm-4:00 pm ET with the U.S. Food and Drug Administration (FDA).  But I WILL say that collectively, over the past year, the diabetes patient community was able to accomplish something truly quite extraordinary.  You should know about that, and even better, you also have a chance to participate in that!

Specifically, in 2013, the diabetes online community started a petition (see http://www.change.org/p/us-food-and-drug-administration-sponsor-a-patient-meeting-on-diabetes), which asked the FDA to devote one of its planned public meetings to diabetes.  For those who don't recall or never heard the sordid history, the short story is that back in 2012, FDA announced that over the next five years, it would be conducting at least 20 meetings on various conditions ranging from Chronic Fatigue Syndrome to Narcolepsy to Irritable Bowel Syndrome.  FDA pre-selected the diseases it would address in the first half of those meetings, yet miraculously, FDA did NOT originally plan to hold a patient meetings to discuss diabetes.  There were only four remaining slots open, and that's where we as a patient community came in.  The basic idea is that such a meeting would help to identify what barriers still exist that prevent the most effective treatments, and what the FDA can do to solve these problems.

I find it interesting that for all the lip service public health officials, including FDA and others, give to diabetes as an epidemic, complete with threatening stats such as more than one in five total U.S. healthcare dollars being spent to care for people with diabetes, and estimated costs of diagnosed cases of diabetes now totaling more than $245 billion (and growing).  Yet apparently, FDA thought it already knew what people with diabetes need and want.  (In fact, I have written in the past that FDA relies almost exclusively on the "surrogate endpoint" of HbA1c, catch my 2007 blog post at http://goo.gl/PSO3qJ), often disregarding everything else, as long as a treatment reduced someone's HbA1c.  But it was the diabetes patient community which felt that FDA excluding diabetes (all types) was a big oversight, and the online petition collected over 7,000 signatures!  That, combined with our increased activism in recent years, including commenting on draft guidance documents, attending review meetings, etc., and I guess that FDA agreed that diabetes activists should be entitled to a meeting with them.

I should add that FDA hasn't really been overwhelmingly in favor of the idea (truth be told, they're used to working with industry [indeed, many FDA staffers are former industry people], but not very used to working with actual patients, so we ARE a bit scary to a group of people used to talking with and amongst themselves), but they're under tremendous pressure from the U.S. Department of Health and Human Services which manages FDA to become more "open" in the ways it does business.  Truth be told, I think the patient-led "Strip Safely" [http://www.stripsafely.com/] initiative kind of scared the crap out of FDA.

Having said that, it does seem that the medical device division within FDA appears to be the most receptive to this particular patient meeting, as the drug and biotech divisions don't yet seem to be completely onboard, with some rumors circulating that one of them actually cancelled its participation in the November 3, 2014 meeting.  But if the first meeting goes well, that may convince the laggard divisions to join in for future patient discussions.

A while back (in July 2014, diaTribe first wrote [http://diatribe.org/issues/66/new-now-next/1] about the upcoming November 2014 meeting, and even offered patients an opportunity to email them with thoughts, see the aforementioned link for details).  As is my nature, I emailed them with two of my biggest concerns.

The first comment I submitted was about FDA's lackluster (which is putting things mildly) follow-up on post-marketing analysis and asked if patients might play a role in that, such as by filing Citizen's Petitions.  For the record, on that issue, several major medical journals show that something like only about half of all post-marketing analysis studies are even submitted as the law requires (and sometimes only because state court challenges mandates it), and even then, it often takes biotech, pharma and medical device companies nearly a decade to do what they agreed to when they received conditional approval for the drugs or devices.  Post-marketing analysis has come to be viewed by industry as a de-facto approval, and FDA's lack of follow-thru and enforcement has helped to create that situation.  There are examples where post-marketing analysis have been submitted (think of type 2 diabetes drugs like Avandia and Actos) which have revealed some truly frightening results and led FDA to add warning labels after they were already being marketed, but even that only happened after doctors like Steven Nissen at the Cleveland Clinic really pushed the issue.

Beyond that, I also wrote about some major concerns I have with the FDA and their biosimilar guidance.  FDA is required, in accordance with details outlined in the Affordable Care Act, to outline guidance for industry on biosimilars.  They did release initial draft guidance (three documents, no less), but a year after the comment period ended, they did something totally unprecedented.  Rather than issuing final guidance, they released yet another guidance document!  That was really confusing for me, and I don't think I'm a stupid person.  How did the new draft guidance document relate to the other three draft guidance document FDA already released?  What would they do next?

My second question was more of a concern.  My readers may recall that I have long been pushing the idea of follow-on biopharmaceuticals or biosimilars.  I first blogged about it in January 2007 asking why the hell we still didn't have generic insulin (see http://goo.gl/QGcSi) for details, and subsequently blogged about the various delays and issues related to that).  Last year, we finally got the original draft guidance FDA released on biosimilars (or "follow-on" biopharmaceuticals as FDA calls them and I submitted a laundry list of concerns, not the least of which was lack of clarity on biopharmaceuticals such as insulin which is governed by the Food Drug and Cosmetics Act, not the Public Health Services Act which governs most other biopharmaceuticals, which they went out of their way to note was only applicable to drugs governed by the Public Health Services Act but did provide some guidance as to FDA's thinking about biosimilars overall.  In my original comments on the first biosimilar draft guidance, I said that FDA needed much more clarity on which instances a biosimilar would be considered bioequivalent to the original molecule (a true generic).  I don't think they can ever really be considered a true generic, as master cell banks and process controls are different with each manufacturer, but unless the FDA spells that out, they've got room for issues, and insulin, which is among the most widely-used biotech products, is likely to see the results first, so I argued that was kind of big deal FDA needed to address.

Lilly's Lantus Biosimilar Has More Hypoglycemia in Patients With Type 1 Diabetes

Right now, because its grandfathered under the Food Drug and Cosmetics Act, insulin is still considered a "small molecule" drug and manufacturers can use several regulatory pathways [including the the 505(b)(2) pathway, which is not available to manufacturers of other biopharmaceutical products like vaccines].  Indeed, Eli Lilly and Company and partner Boehringer Ingelheim already have a biosimilar to Sanofi's Lantus (insulin glargine rDNA origin) pending approval now which Lilly is calling "peglispro", and FDA has already hinted it would be giving them a go ahead on it.  But here's the thing: Lilly will be competing with Sanofi and price, which will likely win them coverage on a number of insurance company formularies.  Normally, that's a good thing, BUT … peglispro is not glargine, and the trial results have already revealed some troubling differences.  FierceBiotech, which was reporting on Lilly's press release how their biosimilar version of Lantus was supposed to be "better" than Sanofi's, this not-so-little tidbit (see http://www.fiercebiotech.com/story/lilly-claims-another-head-head-victory-over-lantus-phiii-diabetes-showdown/2014-09-04 for the article):

Just to quickly re-summarize:


Lilly also was forced to concede that in one of the two Phase III trials [specifically, the leg on patients with Type 1 diabetes] there was a statistically significant increase in daytime hypoglycemic events, an important safety measure, compared to Lantus. Even with an approval, any safety issues could carve out market value from a new diabetes treatment in this hotly competitive space.

The results from the two Phase III studies IMAGINE-1 and IMAGINE-3 in type I diabetes completes the trials planned for peglispro, and leaves Eli Lilly on track to file for an approval in the first quarter of next year.



Holy shit!  This is kind of very big deal, especially for insulin-sensitive type 1 patients with impaired hypoglycemia awareness.  Yet Lilly is busy saying how much better peglispro is to glargine (its not, its merely the same, unless you think that a statistically significant increase in hypoglycemia isn't a big deal).  Do you want your insurance company to switch you to this because its cheaper for them, but is more likely to increase you to have hypos?  I don't!  I expect to express my concerns to FDA!

Back to FDA-DOC Meeting

Back to my comments to diaTribe/Close Concerns about the November 3, 2014 FDA patient meeting.  Following the FDA's draft guidance for biosimilar guidance, FDA then did something unprecedented.  Rather than releasing final guidance on biosimilars, it instead released yet another guidance document.  I must admit that FDA move confused me a lot.  How did the new guidance relate to the original draft guidance?  What is/was supposed to happen next?  If I don't understand it, should other patients be expected to?!

I admit that I was totally confused by this FDA move, but I suspect many others were, too, because FDA has yet to release any final guidance on biosimilars even though it is obligated under the Affordable Care Act to do so.  My question for FDA is if industry and doctors don't even understand what FDA did, how are laypersons in the patient community supposed to?

To be sure, I think I could speak to FDA by myself for a long time with a long list of questions, but I like to think of this move as a first step in actual patient engagement.  Remember, FDA works for U.S. taxpayers to keep patients safe, they do NOT work for industry.

That meeting is scheduled for November 3, 2014 from 1:00 pm-4:00 pm ET.  One area that would help is to take a short, 5-minute survey to help the folks at diaTribe/Close Concerns summarize what areas of concerns matter to people with diabetes, and all you need to do is visit http://diaTribe.org/survey to take that survey.

Friday, January 31, 2014

Hors d'oeuvres Suitable for the Super Bowl

I've never been a big sports fan, in part, because the ticket prices to attend virtually any professional sporting event is beyond ridiculous.  I remember attending my first professional baseball game with my Dad at Fenway Park when I was a kid.  That event remains one of the most memorable events I spent with my father when I was growing up.  But the prices to attend games like that are now simply out-of-reach for many families, and a lot has to do with the salaries for players, although the leagues can afford that with the costly TV broadcasting rights deals they sign for the games.  Its little wonder that minor league sports leagues of all varieties (including the Brooklyn Cyclones baseball team, which has consistently enjoyed sold-out audiences more so than any of the major league games do in New York, including the New York Yankees or the New York Mets) are on a roll.

There's also the not-so-little issue of the NFL still clinging to nonprofit status (exempting the NFL from paying Federal taxes) even though its CEO is better-paid than the CEOs for than many, many for-profit entities (the CEO for the NFL makes $30 million per year, more than both the CEOs for Coca Cola and Walmart earn).  What charitable function does the NFL serve?  Also, Major League Baseball (MLB) dropped its own nonprofit status over a decade ago when a similar complaint came up and has been paying taxes (and wasn't ruined as a result), so why won't the NFL do the right thing?  It's beyond reprehensible, but at this point, unless U.S. lawmakers revoke its nonprofit status, that will continue, and I don't expect that to happen anytime soon.   U.S. Congress finished 2013 as the least productive Congress in American history (see http://ow.ly/t4w6T for more background).  By the way, there's currently a petition on Change.org to revoke NFL's nonprofit status at http://www.change.org/NFLnonprofit if you'd like to see that change.  They've aligned themselves with another organization with a very similar goal at http://www.sacknfltaxbreaks.org/.  You won't be hurting the NFL, but you might get rid of taxpayer giveaways to an organization that clearly doesn't need them.

My personal indifference to major league sports aside, this Sunday is the Super Bowl, which is arguably one of the biggest live events in the U.S. each year.  It also happens to be taking place in New York, rather than some sunbelt location raising the possibility they might consider other locations in the future.  The teams this year come from smaller NFL markets, notably Seattle and Denver (both Washington and Colorado legalized recreational marijuana in the 2012 elections, prompting some nickname this one the "Stoner Bowl" ... indeed, a pro pot-legalization organization has rented several huge billboards outside of the Meadowlands in New Jersey to make that very point, see http://ow.ly/t4xzS for details).  Most of us won't be getting stoned, but a lot of us will be watching the game with family and friends.  Which brings me to today's topic: the food.

Traditionally, Super Bowl Sunday is a day with lots of food, little of which is very healthy food.  If the data is correct, Americans will spend nearly than $1 billion dollars (or more) on Super Bowl snacks alone.  Yet even seemingly healthy appetizers are caloric, with cheese being a very common ingredient (and the calories add up fast), salt, etc.

Rather than turn this post into a lecture about what should or should not be served (after all, I'm guilty of indulging, too!), I thought it might be useful to offer a few alternatives, so when you're munching the deep-fried tortilla chips with some kind of dip (salsa may be OK, but the queso dip, probably not so good), you don't have to regret all of it later.

To be sure, I am always a big fan of Crudité (better known as raw veggies, and they're so easy to prepare, in many cases the supermarket sells them already prepared, but you really should toss the Ranch dressing that comes with the veggies into the trash, more on that in a second).  You can do some cool things with presentation.  This photo shows how a hollowed-out red pepper was used as the bowl for the accompanying dip, so there's no clean up necessary, and it looks good, too.






















Roasted or grilled veggies are also great.  I prefer to prepare my own crudité, but I don't want anyone to spend more time than they have to in the kitchen.

Ranch dressing is an easy and popular accompaniment to go with veggies, but I suggest skipping the Hidden Valley Ranch variety and consider grabbing a bottle of Bolthouse Farms Ranch dressing instead.

Its typically sold in the refrigerated produce aisle of most supermarkets, rather than on the shelf with the shelf-stable bottled salad dressings.  They've (Bolthouse Farms, a wholly-owned subsidiary of Campbell Soup Company since 2012, see http://bloom.bg/1exd18r for the news) taken an American classic (ranch dressing), but instead of using lots of fattening and highly-caloric mayonnaise and cream, they've substituted yogurt instead.  The calorie count for a serving is less than half of what typical varieties of ranch dressing contain (45 calories vs. 140 for a serving of Hidden Valley Ranch dressing), so you won't do quite as much damage, and I think it tastes the same.  I would guess your fellow Super Bowl watchers probably won't even notice the switch.


However, there are other things you can do, depending on how creative you want to get.  Since many people spend the Super Bowl with friends and/or family, they may be asked to bring a hors d'oeuvre to the party.  Aside from crudité and lower-calorie ranch dressing, consider a re-imagined version of a classic appetizer recipe instead, as well the following easy ideas as well.

One recipe that I've tried and rather like I found in the newspaper a few years ago (in 2012).  This one is the most complicated (not that its especially difficult or complex) of the hors d'oeuvres I will share in this post, the others require little effort and can be prepared in minutes.

An Associated Press journalist named Alison Ladman re-imagined a seemingly healthy appetizer whose ingredients aren't nearly as as virtuous as the name implies: Spinach and Artichoke Dip.  Her original article can be found online (the Salt Lake [City] Tribune has it on its website at http://bit.ly/1d8tSxe), but I think the opening paragraphs say it all:

"Spinach and artichoke dip sounds like it should be a virtuous treat. After all, it's loaded with vegetables.

Trouble is, it's usually more mayonnaise and cheese than spinach and artichoke. So we decided to see if we could come up with a version that isn't so out-of-sync with healthy eating."

This recipe takes a bit of prep-work but the crudité will save you time, and I'll offer another easy recipe to accompany this, so you can bring a few tasty and interesting items to your Super Bowl gathering.

Below is the article text (its short) for this recipe remake.  A downloadable version which I found online follows.


Spinach and Artichoke Dip
By Alison Ladman, Associated Press
First Published: April 12, 2012

Spinach and artichoke dip sounds like it should be a virtuous treat. After all, it's loaded with vegetables.

Trouble is, it's usually more mayonnaise and cheese than spinach and artichoke. So we decided to see if we could come up with a version that isn't so out-of-sync with healthy eating.

First order of business was to nix the mayonnaise. But, of course, we wanted something that had a great creamy texture and that could be heated. Greek style yogurt blended with low-fat cream cheese (Neufchatel) worked beautifully. It even added a subtle tang, which we enhanced with some lemon zest for a nice spring flavor profile. Some fresh herbs took it ever further.

Next up, dealing with the cheese. We handled the inner gooey-ness with the aforementioned cream cheese. But often there also is a pile of cheese or bread crumbs (or both) on the top. After it's broiled, we wanted that textural contrast and the toastiness that comes with it.

We found that crushed and seasoned whole-grain crackers worked well. Just note that different varieties of crackers can have widely varying nutrition. So be sure to read the labels carefully to select a whole-grain cracker with modest amounts of fat and calories. Aim for around 100 to 120 calories and 4 grams of fat per serving. You'll also want about 3 to 4 grams each of protein and fiber.

Lastly — and most importantly — was upping the amount of spinach and artichoke. We went with canned artichokes for ease. They also are available frozen. Either way, be sure to get the variety in water, not oil. Fresh baby spinach got a quick saute with onion and garlic before being added. Serve the warm dip with whole-wheat pita chips, baked tortilla chips or veggie sticks.

Spinach and Artichoke Dip
Makes 8 servings

Ingredients:

  • Cooking spray
  • 1 ounce (1 serving) whole-grain crackers, crushed
  • 1/4 teaspoon garlic powder
  • 1/4 teaspoon onion powder
  • 2 tablespoons Parmesan cheese, grated
  • 6 ounces plain nonfat Greek yogurt
  • 4 ounces low-fat cream cheese (Neufchatel)
  • 1 teaspoon lemon zest
  • 2 teaspoons fresh oregano, minced
  • 2 teaspoons fresh mint, minced
  • 1/2 teaspoon salt
  • 1/2 teaspoon ground black pepper
  • 1 tablespoon olive oil
  • 1 small yellow onion, diced
  • 1 clove garlic, minced
  • 1 (5-ounce) package fresh baby spinach
  • 1 (14-ounce) can artichoke hearts, lightly chopped
Heat the oven to 400 degrees. Coat a small casserole or gratin dish with cooking spray.

In a small bowl, combine the cracker crumbs, garlic powder, onion powder and Parmesan. Set aside.

In a food processor, combine the yogurt, cream cheese, lemon zest, oregano, mint, salt and pepper. Pulse until smooth.

In a large skillet over medium-high, heat the oil. Add the onion and garlic and saute until soft, about 5 minutes. Add the spinach and cook until soft and any liquid has evaporated, about another 5 minutes. Remove from the heat and stir in the artichokes and the yogurt mixture. Spoon into the prepared dish.

Sprinkle the cracker crumb mixture over the dip and bake for 10 to 15 minutes, or until hot. Serve warm.

Approximate nutrients per serving: 120 calories, 5 g fat, 2 g saturated; 10 mg cholesterol; 560 mg sodium; 3 g fiber.

Copyright 2012 Associated Press. All rights reserved.

You can download an Adobe Acrobat (PDF) version of this recipe HERE.

The next two appetizer ideas were courtesy of Health magazine (see http://tinyurl.com/o3nba7u for these and others), but they were so quick and easy that they were definitely worth trying at your next party, whether its for the Super Bowl or some other occasion.  Of course, nice photos are always a selling point!

Med Coast-Bites
66 calories, 2g fat

Spread 8 ounces hummus evenly onto baked pita chips (12-ounce bag). Shred 1 large carrot; distribute evenly over chips. Zest rind of 2 lemons; place a few pieces atop carrot.

I've added some of my own feedback on this recipe one because this is a recipe that lends itself to some creativity IMHO.

Alternatives to the lemon zest (for variety and flavor) include various dried herbs and spices.  To make things easy, I've found it easy to use Mrs. Dash seasoning blend varieties that you like (see http://www.mrsdash.com/products/seasoning-blends).  I'm personally quite fond of the Onion & Herb Seasoning Blend (although my local supermarket no longer carries it) as well as the Lemon Pepper Seasoning Blend, but as I said, the selection is yours.  More creative alternatives include using ingredients like powdered wasabi, which I personally really like (it can usually be found in Asian supermarkets).  A blend with salt is great (I use 2 tbs. or wasabi and 2 tsp. of salt, though I would skip the salt for this particular recipe because its really not needed here.  The trick is to use these ingredients to enhance the flavor, just don't use too much.  Remember, there's already flavorful hummus in this recipe (and even there, you can use varieties other than plain tahini-flavored hummus, although there's nothing wrong with that).  Mix things up and make a couple different versions, just be sure your Super Bowl guests or friends know what each is.

Caprese skewer
46 calories, 4g fat

Using 2 pints cherry or grape tomatoes, 1 pound bocconcini (fresh mozzarella), and 1 bunch fresh basil, thread ingredients onto skewers. My personal preference is the yellow and orange tomatoes because the red ones are rather flavorless.  Sprinkle each skewer with sea salt and black pepper; drizzle with extra-virgin olive oil.

So these are my contribution to Super Bowl Super Bowl XLVIII hors d'oeuvres menu.  Any other suggestions?  Feel free to add them to the comments.

Monday, January 27, 2014

Recent FDA Moves Suggests Agency Is Again Taking Its Role of "Protecting Public Health" Seriously

As a patient with type 1 diabetes, I have found myself at odds with the U.S. Food and Drug Administration (FDA) on a number of things the agency has done in recent years (actually since the 1980s), and perhaps even more so in recent years.  In fact, I once joked (only halfheartedly) that the acronym "FDA" stood for Fatal Drug Administration.  Indeed, for a number of years (under the leadership of chief Dr. Andrew von Eschenbach especially, he pushed for FDA to serve what he called its "clients", meaning the companies that the FDA regulates, rather than protecting public safety).  Staff in areas for brand new drugs exploded, while the queue of unapproved applications in generics also grew, yet the FDA never asked Congress for user fee authorization in generics during that time.  However, at the end of 2013, the FDA took two very important moves that might just give me reason to reconsider my belief that the FDA was looking out more for industry than it was for patient safety.  Both relate to the "Food" responsibilities at FDA, but given that cardiovascular disease is the #1 killer of people with diabetes, the first one is especially relevant, while the second one relates to big agribusiness routine abuse of medicines and has resulted in a rise of antibiotic-resistant viruses.

Item #1: Obituary for Twinkie the Kid?

On November 16, 2012, Huffington Post featured an article entitled "Twinkie The Kid, Dead At 85" (see http://huff.to/1dINwQt).  The article, of course, was a parody of the then-current news that Hostess, the manufacturer of Twinkies had filed for liquidation in a bankruptcy filing.  The maker of Twinkies cakes had flirted with death several times in recent years, and in 2012, when the parent company, Hostess (which had various names over the years, including Continental Baking Company and Interstate Bakeries) had finally filed for bankruptcy after failing to reach an agreement with the company's unions.  Unlike a bankruptcy reorganization, this one was a liquidation, which meant the company and all of its brands were dismantled.  But as author Mark Twain once wrote: "The reports of my death are greatly exaggerated", and so too was the reported death of the über-processed, junky snack food known as Twinkies.  Indeed, the Twinkie re-emerged to much fanfare under new ownership a year later (in 2013).  But the obituary for the Twinkie in Huffington Post may have been a premonition, only this time, it won't be finances or unions that kill it - it will be the recipe for Twinkies itself.

That's because the Twinkie (and virtually all Hostess cakes) is made primarily from hydrogenated fats.  It has a bunch of other highly-processed ingredients, some of which are mined, and an entire book entitled "Twinkie, Deconstructed" [http://www.twinkiedeconstructed.com/] by Steve Ettlinger was written to try and explain the ingredients in Twinkies.  (That book, incidentally, is highly-entertaining reading!)  Indeed, the creamy filling is pure hydrogenated fat and sugar.  The cake itself also has a lot of sugar and hydrogenated fat, which explains why they seemingly never spoil.  But the new nemesis of the Twinkie may be the U.S. Food and Drug Administration (FDA), and unless the company suddenly gets creative, because all of the Hostess cakes (including the namesake Twinkie, as well as Ding Dongs, Ho Hos, Chocodiles and others depicted in the commercial featured in the Huffington Post article) will cease to exist.  Nostalgia won't save them from using a banned ingredient, namely hydrogenated fat.

That's because in early November 2013, FDA did something doctors and nutritionists had been advocating for decades: it finally took steps to remove artificial trans fats (hydrogenated or partially hydrogenated oils) from the U.S. food supply.  See the news in the Federal Register at http://1.usa.gov/1aY5Ubk and a separate, more user-friendly article about the announcement from the FDA at http://1.usa.gov/1bsRrRy.

About Trans Fats

Trans fats are created when hydrogen is added to vegetable oils to make them more solid (vegetable shortening, a.k.a. "Crisco" is the usual result).  The result is an artificial product said to accumulate as plaque in the arteries.  If the FDA's decision is finalized, partially hydrogenated oils (trans fats) will soon be classified as food additives that can no longer be used without prior FDA approval.  A  final ruling by the FDA won't come until after a 60-day comment period, but Dr. Margaret Hamburg and the FDA's top food official, Michael Taylor, left little doubt that the agency's goal was to completely remove trans fat from the U.S. food supply.  The FDA and CDC jointly estimate that totally eliminating trans fats from the U.S. food supply could prevent 20,000 heart attacks and 7,000 deaths due to heart disease each year.

Its hard to believe it now, but once upon a time, trans fats were actually claimed by their promoters to be healthier than the lard, butter and the saturated animal fats they often replaced.  However, mountains of data since proven they are actually even worse for us than saturated fats are when it comes to heart disease, which is a major U.S. killer.  In 2006, after a campaign by public health advocates, the FDA finally started requiring food companies to add trans fats to food labels.  (On a related issue, there was news recently, see http://ow.ly/t2mG6 for details, that the FDA would likely be revising food labels in the near future.  The FDA won't say exactly when the changes will come, or what the new labels will include. But we're likely to see changes that make it easier to see calorie counts, more up-to-date serving sizes [right now, serving sizes are a joke] and more detailed information on added sugars including high fructose corn syrup.)  That was a good start, but the FDA's latest move may actually be the impetus to end routine use of these toxic ingredients in the U.S. industrial food supply found in your local supermarkets.  Indeed, trans fats would become an ingredient "not generally recognized as safe" and would need special permission from the FDA to be used.  The commercial food industry, especially commercial bakeries such as Nabisco (part of Kraft) will need to do some serious soul searching to find practical alternatives which are in bread, cookies and various other products including cake frosting sold in supermarkets.

Trans fats are very common in highly-processed foods, although they are also very common in commercial baked goods like biscuits, pie crusts, and frostings that aren't hand-made.  The FDA once estimated that in the late 1990s, 95% of prepared cookies, 100% of crackers, and 80% of frozen breakfast products sold in the U.S. contained trans fats.  The frying oils used in restaurants were also rich in them at that time, but the use of trans fats in frying foods (at places like McDonalds) has indeed declined significantly in recent years so that they’re relatively uncommon in fried foods sold in fast food joints today.  According more recent data from the FDA, trans fat intake among Americans declined from 4.6 grams per day in 2003 to around 1 gram in 2012.  Michael Jacobson, executive director of the Center for Science in the Public Interest, estimates that today, 75% of the trans fats is already is gone from the nation's food supply.  But, they still remain in things like Twinkies, so the FDA move is a good move.

The scientific evidence against these staples in processed foods is pretty overwhelming, namely that they provide absolutely no nutritional value at all, yet are implicated in the prevalence of heart disease (trans fats aren't the only factor, but it's a notable one).  That's why the FDA's announcement on November 7, 2013 that for the first time, it believes that trans fat can no longer be considered "generally considered as safe" drew a lot of praise from doctors.  Trans fats are made by adding hydrogen to vegetable oil (most commonly, genetically modified soybean oil) in a process that is hardly new.  In fact, in what was perhaps a great irony, Paul Sabatier won the 1912 Nobel Prize in Chemistry for discovering the hydrogenation method that activists are now fighting to remove from our food today. His research detailed the way nickel could be used as a catalyst to create chemical reactions between hydrogen molecules and other compounds, which laid the groundwork for the creation of hydrogenated oils.

Why Industrial Food Producers Loved Trans-Fats

Trans fats became very popular because of their versatility in industrialized food production which dominates U.S. supermarket shelves.  Trans fats make processed foods "shelf-stable," able to stay on supermarket shelves for months without going bad.  Fast food restaurants also liked trans fats because they could be used repeatedly in commercial deep fryers without having to be replaced, according to the American Heart Association.  As already noted, that industry largely abandoned trans fats nearly a decade ago.

Kantha Shelke, a scientist with the Institute of Food Technologists in Chicago, told NPR that the the use of trans fats in things like cookies or doughnuts means the products don't leave a ring of oil behind on a paper towel and don't start tasting rancid after a few weeks.  Also, this type of fat doesn't have a strong taste of its own so you can use lots of it without ruining the flavor.

"It's really absolutely perfect [for industrial food production], and it's also perfect for the American style of shopping: You buy boxes and boxes of crackers, put them in your pantry," says Shelke. "You open this box six months or eight months or a year later, and it would still taste and smell just as good as it was on the day you bought it!"

The use of these fats really exploded as the food system in the U.S. became increasingly industrialized, but so did the adverse the health effects.  However, since the FDA started requiring labeling of trans fats separate from other fats, much of the food industry has already started to migrate to more traditional oils, and trans fat usage has declined as food manufacturers and processors found alternatives.  In a statement, the Grocery Manufacturers of America said that since that 2005 food manufacturers have already lowered trans fats in products by more than 73%.  However, the FDA says that today, 12% of all packaged foods still contains a partially hydrogenated oil, the formal name for trans fats, which is why the FDA feels the time is right now to eliminate them completely.

U.S. Not Alone in Efforts to Get Rid of Trans-Fats, WHO Also Advances the Issue

The U.S. is hardly alone in the move to try and eliminate these industrial fats from its food supply food.  In 2004, Denmark made it illegal (see http://ow.ly/sZQto for more) for any food to have more than 2% trans fats. Offenders risk hefty fines or even prison terms.  Other countries are also working to reduce trans fat in their food supplies. Policies in Brazil, Costa Rica, the Netherlands and South Korea have proven effective over the past two decades (showing that countries from Latin America to Europe to Asia are dealing with the issue), the World Health Organization says. The WHO has also called for completely eliminating trans fat from the global food supply, though the WHO lacks any enforcement capability.

Giant food-processor Cargill Inc., which now sells partially hydrogenated shortening to commercial customers, said it will help them switch to alternatives.  Another big maker, Archer Daniels Midland Co., said it [trans fats] is a steadily declining business and that it sells low- and zero-trans-fat oils.  These big industrial food suppliers are now working with clients to find suitable alternatives.

Junk Foods That Are Ahead of the Curve?

Pepsico's Frito-Lay snack unit saw the handwriting on the wall nearly a decade ago and did take a lead in product reformulation when it began selling "zero trans fat" snacks before all packaged foods were required to list the amount of trans fat on the nutrition labels.

Nevertheless, some of the company's snacks, now cooked in corn, canola and/or sunflower oil, still fall into the 0.0 to 0.5 gram range, a spokesman said.  That's because the FDA permits them, if there's less than half a gram of trans fats per serving, to list the amount of trans fats in their products as zero.

Other food categories may require modification.  They remain staples in things like boxed cake mixes and frostings, as well as such mundane categories as breakfast cereals (for example, Post Fruity Pebbles sugary breakfast cereal relies on trans fats).

Food processors should not be surprised; the moves to eliminate trans fats in restaurants (notably, New York City banned them for use in restaurants in 2004 and other big cities including San Francisco did the same) has been growing and the industry has (for the most part) found suitable alternatives, including non-hydrogenated, genetically modified soybean or canola oil that is used for deep fat frying many foods.  Fast food chains have already eliminated trans fats from much of their menus (except for their baked goods, such as hamburger buns, which come from third-party suppliers who rely heavily on trans fats in their production and so the products will stay fresher, longer) a number of years ago, and no one's french fries or chicken nuggets suddenly disappeared as a result.

The evidence has been mounting against trans fats over the past few decades after numerous studies linked trans fat to higher LDL, or bad cholesterol, as well as to heart attacks and strokes. The Institute of Medicine said in a widely-cited 2002 report that "there is no safe level" of the ingredient (see http://1.usa.gov/1hF26wQ for reference).  As I noted, the turning point really came in 2006 when the FDA mandated that processed food makers must disclose the presence of trans fat on their nutrition labels, at which point food manufacturers began (in earnest) switching to more traditional oils rather than have the negatively-perceived ingredient show up on their "Nutrition Facts" labels.

Microwave Popcorn, Commercial Baked Goods Still Loaded With Trans-Fats

Aside from the products already mentioned, certain food products are still heavily dependent on trans fats.  For example,  things like microwave popcorn, frozen pies and all kinds of mass-produced baked goods. Often, food companies use just a little bit, but the new rules would require them to reformulate their recipes.  A complete ban on trans fats would be a bigger deal for food manufacturers, according to Ms. Shelke. She says food companies can drop the trans fats, but their products won't be quite the same.

"They have to go back to re-educating consumers that cookies don't last forever," says Shelke.

Although the packaged baked goods might have a shorter shelf life, the FDA is hoping consumers' lives will be be longer as a result.

The FDA move seemed to have few opponents, even among residents of states generally opposed to big government.  One Houston resident, when asked about whether the move was too "nanny state", wasn't opposed to the FDA move.  He rationalized his response as follows:

"I think the government should have control over things that we create, just like any drug," the man said. "I don't want the government telling me I can't eat duck fat. But telling me I can't eat crude oil that's been refined and turned back into something that resembles margarine I have no problem whatsoever with. That isn't something you're getting out of an animal. You cannot make trans fats in your home kitchen. So why the hell should a company be able to sell them to you when they know it's bad for you?"

The FDA press release on the announcement can be found at http://1.usa.gov/1dIVusV and the announcement in the Federal Register with information such as the docket number and whom to send comments to can be found at http://1.usa.gov/1fhYdhA.  Comments to the FDA were due on January 7, 2014, although U.S. law permits public comments on any guidance at any time, even if the practical impact may result in the agency giving late comments less consideration (if any at all).  As to whether “Twinkie the Kid” can cheat this particular death round remains to be seen.

Item #2:  Routine Use of Antibiotics in U.S. Industrial Meat Production

Separately, on December 11, 2013, the FDA took steps that are within the agency's authority to crack down on widespread use of antibiotics in the nation's food supply.  See coverage in the New York Times at http://nyti.ms/1bXhYeO) and the FDA’s announcement at http://1.usa.gov/1cASPF0.

As the Los Angeles Times reported (see http://lat.ms/Mljay8) at the beginning of 2012, only 20% of the antibiotics sold in the U.S. are actually given to people who are sick with bacterial infections, such as ear and urinary tract infections or pneumonia.  In fact, most of the penicillin, tetracycline and other antibiotic drugs used in the U.S. today are given to livestock -- and to make matters even worse, most of the livestock given these antibiotics are aren't even sick.


"We feed antibiotics to sick animals, which is completely appropriate, but we also put antibiotics in their feed and in their water to help them grow faster and to compensate for unhygienic conditions. said Dr. Gail Hansen, a veterinarian and senior officer for the Pew Campaign on Human Health and Industrial Farming, a project aimed at phasing out overuse of antibiotics in food production, who added "If you have to keep the animals healthy with drugs, I would argue you need to re-examine the system. You don't take antibiotics preventively when you go out into the world."

The FDA's latest move is (at this point) voluntary and will be phased in over a three year period because the FDA believes that's actually the fastest and most effective way to achieve its goal.  The FDA told Reuters that approximately 25 to 27 companies would be affected by the voluntary three-year phase-out of the use of antibiotics in the raising of animals for food production.  William Flynn, deputy director for science policy at the Center for Veterinary Medicine at the FDA, said during a call with reporters that Zoetis Inc. and Eli Lilly & Co.'s Elanco unit sell a large percentage of those products and it has already started speaking with those companies about compliance with the phase-out.

As might be expected, the big meat processors like Smithfield Farms, as well as others like Tyson Foods, Inc., Hormel Foods Corp. and others all claimed that the FDA move was a huge mistake, but don’t believe them.  Critics say they need to clean up their act, although their response (so far) has been to push for so-called “Ag-gag” bills, which is already the law in Utah, Iowa, Missouri.  Similar legislation has been appearing, and reappearing in almost a dozen other states, including Nebraska, Indiana, Wyoming, Arkansas, North Carolina, Minnesota, Pennsylvania and New Hampshire, which basically makes it a criminal offense to even photograph industrial "farms" (see http://wny.cc/1esvu5W for an interesting discussion on that) that’s now routine in modern American farming.  Many of these bills are reportedly efforts to combat terrorism, eco-terrorism or otherwise (at least if one believes the bills’ sponsors in the legislature), and yet, the real outcome seems to be criminalizing information.

However, the FDA's move on antibiotic use was actually precipitated by a number of true citizen's petitions which the FDA basically ignored, followed by lawsuits which the FDA lost.  In other words, the FDA was sued and lost, hence it had to do something on the matter, and finally moved in 2013 to actually do so.  Some of the petitions and lawsuits go back to 2009 or even before.  More recently, on March 23, 2012, the FDA lost a lawsuit filed by the Natural Resources Defense Council, Center for Science in the Public Interest (CSPI), Food Animal Concerns Trust (FACT), Public Citizen, and Union of Concerned Scientists (UCS).  One Court noted the issue in its 2012 decision: "Research has shown that the use of antibiotics in livestock leads to the development of antibiotic-resistant bacteria that can be--and has been--transferred from animals to humans through direct contact, environmental exposure, and the consumption and handling of contaminated meat and poultry products."

On June 4, 2012, the courts ruled that the FDA had been dragging its feet for years and ordered the FDA to take action in order to protect public health from the overuse of antibiotics in animal feed by instructing FDA to reconsider two previous citizen petitions which urged the agency to revoke approvals for all non-therapeutic uses of antibiotics in livestock production.  For years, scientists, health care organizations, and government agencies had warned that the widespread use of antibiotics to hasten animal growth and compensate for unsanitary and over-crowded feedlots resulted in diminishing effectiveness of these essential medicines to treat infections in people.  The term antibiotic resistance has become more common in recent years.

"The Court's order pushes the agency one step closer to meaningful action to curb the dangerous overuse of antibiotics in animal feed," said Avinash Kar, NRDC health attorney. "The Court calls out FDA's protracted foot-dragging on the problem of antibiotic resistance and requires the agency do its job to protect our food, our health and our families."

In recent years, some pathogens have evolved to withstand the drugs (antibiotics) that previously was used to kill them.  The World Health Organization sees this threat as dire. "A post-antibiotic era, in which common infections and minor injuries can kill, far from being an apocalyptic fantasy, is instead a very real possibility for the 21st century," the organization notes.

Urinary tract infections caused by drug-resistant E. coli are increasingly common, as are infections caused by methicillin-resistant Staphylococcus aureus (MRSA) — rates of which doubled at academic hospitals between 2003 and 2008.  The WHO also notes that gonorrhea, which used to respond well to common antibiotics, "may soon become untreatable as no vaccines or new drugs are in development."

However, the most recent move by the FDA was greeted more favorably by the meat industry but decidedly less so by critics.  The Natural Resources Defense Council, a non-profit environmental advocacy group that was among the organizations that sued the FDA for changes bashed the FDA's plan, saying it fails to require any change in the use of antibiotics."

FDA's policy is an early holiday gift to industry," NRDC health attorney Avinash Kar said in a statement. "It is a hollow gesture that does little to tackle a widely-recognized threat to human health. FDA has essentially followed a voluntary approach for more than 35 years, but use of these drugs to raise animals has increased."

The Center for Science in the Public Interest noted in a statement the proposal "requires the drug companies who profit from sales of their drugs to initiate the process. The good news is the agency has pledged to evaluate levels of compliance and inform the public after 90 days if the drug industry is cooperating with the relabeling effort."

Having said this, even this move (however late and toothless) is still a much-needed step in the right direction, although its one which some would say the U.S. Department of Agriculture (USDA) kind of promoted (at least unofficially) to address downright filthy feedlots routinely used in industrial meat production.  To give you an illustration of just what this means, animals are fed antibiotic-laced food and stand in 1-2 inches of feces.  The runoff pollutes waterways around these "farms".  According to Iowa Citizens for Community Improvement, a group that is trying to fight factory farming in Iowa, using data from the state's Department of Natural Resources, the number of "impaired waterways" in the state over the past decade, although all of that degradation can't be laid at the feet of livestock farms — Iowa also has massive amounts of corn farming, which also results in leaching of algae-causing nitrogen and phosphorus. However, farming hogs has scaled up over the same time frame (see http://bit.ly/1ekYwF5 for more details).  On the latter issue, I should note that the Chinese seem very eager to copy U.S. industrial food production methods to feed its billion people inexpensive meat.  China has been on a meat-eating binge, having doubled its consumption in the last two decades of economic growth.

In September 2013, Virginia-based pork producer Smithfield Foods Inc. was acquired by Shuanghui International Holdings Ltd., but the company legally changed its name on January 21, 2014 to the less-distinctively Chinese WH Group Ltd., in a $4.7 billion acquisition deal, meaning the company sold at a 31% premium.  The deal made Smithfield shareholders very happy, and also passed the Justice Department's requirements.  China itself has been plagued by routine food processing scandals at home (does anyone remember the poisoned infant formula incident that made world headlines in 2008?), so the Chinese government viewed the Smithfield acquisition as a way of helping the country produce meat more cheaply at home using methods that are now already widely-deployed in the United States.

China seems to want to emulate U.S. food industrialization, regardless of the health consequences.  I suppose its marginally better than what they have presently, but one could hardly call it an “advancement”, but they’ll have to deal with the longer-term health consequences down the road, something the U.S. has been slow to do itself.

On the issue of industrial meat production, a relatively new documentary released on December 10, 2013 in cooperation with Rolling Stone magazine (see http://rol.st/ID5xs3) gives a closer look at what American "farming" looks like today.  I'll give you a hint: images of animals grazing happily on open fields is a big myth.  The reality, as documented to some extent in the film I addressed a few years ago "Food, Inc." (see my post at http://goo.gl/X0iiun for details), is very different.  Although the Rolling Stone film focuses more on the issue of animal cruelty which is an eye-opener by itself, the conditions (which China now wants to adopt) have certainly become a major health threat that has grown exponentially over time.

In the end, these two recent FDA moves, regardless of what prompted them, does suggest (to me, at least), that the era of the FDA serving "clients" it is tasked with regulating, is less important today than is the goal of public safety.  That certainly doesn't mean things are perfect at FDA.  There's still a revolving door between senior executives in the drug and biotech companies into the management roles at the FDA (and USDA) which is a significant conflict-of-interest that still hasn't been resolved, but it IS a step in the right direction.

Tuesday, December 31, 2013

Little-Noticed Diabetes Care Developments of 2013

As we approach the new year (2014!), although I haven't blogged as much as I did a number of years ago, there were a few things which, in my opinion, deserve acknowledgement as they relate to diabetes care.  One of the biggest (perhaps), yet less acknowledged, developments was mergers and acquisitions in the diabetes care space.  Although I follow this stuff, sometimes even I lose track of who acquired who and what their new names are (when they change the name of the company).

Bristol Myers Squibb: In Again, Out Again (... Of Diabetes Care, That Is).  Novo's Danish Delusions.

My readers may recall that last year (see http://on.wsj.com/Kh9xic for details), San Diego-based Amylin Pharmaceuticals was acquired by the pharma giant Bristol Myers Squibb (BMY), a company that was (after Eli Lilly & Co.) once the second-largest American drug company to sell insulin in the U.S. (in those days, it was sold under the E.R. Squibb & Sons, Inc. brand name and did so until the mid-1970s).  Various mergers and acquisitions (including Squibb's being acquired by Bristol Myers in 1989) over the years and production problems led the company to turn to a largely unknown (to Americans and Canadians) Danish company known as Novo Nordisk A/S to supply insulin through a joint venture which relied on Squibb's American salespeople to merchandise the product, and Novo's manufacturing sold by a joint venture known as Squibb/Novo, Inc. until 1989, at which point, Bristol Myers Squibb executives sold the company's share of the joint venture to Novo Nordisk outright and exited the U.S. insulin market completely.  I should note that 1989 was also the year that two separate, Danish rival insulin manufacturers merged to form Novo Nordisk A/S, previously Novo and Nordisk were independent entities.  Novo did see sales grow with the joint venture, hence the acquisition established the company as a viable competitor in the U.S. insulin market whereas the company was almost completely unknown to North Americans prior to the 1980s.  However, insulin pens didn't propel the company to become a major player as it did in Europe, its ability to navigate the managed care environment and sell itself to the formulary managers did.  Ironically, Diabetic Investor David Kliff thinks Novo Nordisk management is naïve to think its products are immune from competition (see http://onforb.es/JIsWbo for his write-up).  I will say that in addition to losing Express Scripts and Kaiser Permanente this year, the company has also seen a newly-aggressive Lilly grab more market share during the past few years, whereas Lilly had let its diabetes business slide previously.

Novo Nordisk followed a somewhat similar strategy in Canada.  The Canadian government under Prime Minister Brian Mulroney liquidated the birthplace of insulin, Connaught Laboratories, Ltd. around the same time, although I believe it was sold to what was then Aventis (now Sanofi) because by that time, Novo had already established its own manufacturing facility in Canada.  BMY, on the other hand, had pretty much avoided diabetes treatments (for type 1 or type 2) until more than a decade later when it bought Amylin.

In any event, BMY re-emerged as a player in the diabetes space when it acquired Amylin.  I should note that the company's CEO left the company to run Israel-based drug giant Teva (best known for generics) for a bigger paycheck, only to leave a few months later after a disagreement with someone on the board of directors.  He and the rest of Teva's management team see opportunity in proprietary, patent-protected drugs rather than simply competing with low-price generics companies (several from India) as well as others like Perrigo (headquartered in Michigan, more on them later) which just closed on Elan, a big Ireland-based generics manufacturer (see http://prn.to/1bQBMOh for details).  Rival BMY moved in a different direction when it comes to diabetes.

AstraZeneca: A Newer Player In Diabetes Care, But Now A Pretty Big One

Without getting too far off-topic, the irony is that BMY had decided less than a year after acquiring Amylin, to sell its diabetes business as a whole to AstraZeneca (a.k.a. "AZ", which was a joint venture partner to market products like Symlin and Byetta in Europe) which seemed a tad like deja vu for long-timers who remember the days when Novo Nordisk had absolutely no brand recognition in the U.S.  AZ is kind of unknown in the U.S. diabetes market, much as Novo Nordisk was in the 1980s, but it cannot be discounted.

AstraZeneca, itself the result of a 1993 merger between Sweden's Astra Pharmaceuticals and the larger UK rival Zeneca Group plc, is kind of struggling these days with a number of patent expirations, and relatively few likely drug prospects in its own development pipeline.  The acquisition gives it sales and a few likely drug approvals in the coming years.  AZ had an autoimmunity treatment (which it was working with a Cambridge, MA startup known as Tolerx) for type 1 diabetes in its pipeline which failed in clinical trials (see the news at http://bit.ly/1fWjexj), and many of the company's other products are no longer patent protected.  It has seen its share in the Type 2 GLP-1 receptor agonists, which mimic the effect of glucagonlike peptide- 1 space (Byetta) shrink as Novo's Victoza has grabbed a bigger slice, but there are expectations that its extended release version to be known as Bydureon could reverse that in the not-too-distant future.  Also, Novo Nordisk lost the massive Express Scripts PBM account, which may favor AZ.  AZ needed the diabetes business more than BMY did, although I question whether the company can effectively manage the business, though it certainly has every incentive to make it work.

Teva Could Emerge As a Bigger Player in Diabetes than AstraZeneca in the Future

Teva already sells a number of type 2 generics, but its also one of the few (aside from Novartis' Sandoz unit) companies that could emerge as a major biosimilar manufacturer (although Lilly is already discussing a new-and-improved version of Sanofi's Lantus whose patent is due to expire in a about a year).  Aside from that, the company has licensed the rights to one of the few autoimmunity treatments that hasn't [yet] failed in clinical trials (Diapep 277), which its licensed from another Israeli company known as Andromeda (see my post HERE for background).  Of note is the fact that on December 18, 2013, Andromeda announced that the first patient had been dosed with DiaPep277 for the treatment of type 1 diabetes in its Extension Study to the Phase 3 Clinical Trial known as DIA-AID 2.  The 24-month extension study is designed to evaluate long-term safety, tolerability, and the effect of DiaPep277 on the ability of patients to maintain glycemic control for 2 additional years following the completion of the DIA-AID 2 confirmatory study. DIA-AID 2 is scheduled to be completed at the end of 2014, and is being conducted in medical centers in the USA, Europe, and Israel.  Catch my Tweet on that below, or HERE.

Nipro Diabetes Care: You May Not Know Them, But You May Know Them Soon (or at least you'll know their products)

My readers may recall that a few years ago, I wrote about Nipro Diabetes Care (see my post HERE).  In hindsight, my write-up wasn't terribly flattering (to Nipro), but my perspective was that Walmart Stores, Inc. was getting big price breaks from its new supplier (Nipro), but wasn't passing the savings on to consumers.  However, on my most recent visit to Walmart, the company had cut the prices for its liquid glucose products by $0.20.  Thanks Walmart, better late than never, especially for a company whose Q4 2013 sales are likely to disappoint institutional investors, and you wonder why?  In any event, a Nipro made a little-noticed but pretty big move that deserves to be acknowledged here.  My readers may recall that in January 2013, Perrigo acquired CanAm Care (see the press release at http://prn.to/1doc59j).  They are a big supplier of store-branded lancets and glucose tablets, although it also sells glucose tablets and liquids under the Dex4 brand name.  In any event, my longtime readers may recall that I disclosed that CanAm care relied upon a small, privately-held New Hampshire based company known as P.J. Noyes Company (I wrote about it HERE) to make its glucose tablets and bottle its Dex4 Liquid Blast liquid glucose treatments.  As it turns out, in August 2013, rival Nipro Diabetes Care acquired P.J. Noyes (see the Businesswire press release of the acquisition at http://bit.ly/1dodRai) the contract manufacturing company CanAm users to make these things.

Not only did Nipro snag the massive Walmart account from Perrigo, but it also acquired the very company that contract-manufactures its glucose tablets and liquids!  This undoubtedly puts Perrigo's CanAm Care unit in a rather uncomfortable position.  As part of a bigger drug manufacturer, CanAm can theoretically bring production in-house, but it may not have the ability to do everything right now, and the company is very busy digesting its big Elan acquisition (the company which is headquartered in Michigan, but is now legally based in Ireland thanks to tax benefits), so the company to watch in this space is (for the moment), Nipro, although as I wrote way back in 2006 (see my post HERE) there are other players such as New Jersey-based Raritan Pharmaceuticals which might step in given the change-in-hands seen at P.J. Noyes.

Time will tell.

However, we have seen Nipro make some subtle changes (a number for the better), such as removing less popular flavors from the bottles of glucose tablets that patients aren't complaining about, removing the inner seal to the glucose liquids to make them easier to open, so this development could be an interesting one.  I would expect to see Perrigo to be more aggressive to try and retain its share of the lucrative private-label business (sold under the pharmacies' brand names), but whether this translates to savings for patients remains to be seen.  However, Nipro did switch to shorter bottles for its glucose liquids that resemble energy (caffeine) shots so as to be less conspicuous.  They also lack an inner seal making them easier to open (good news if your hands are shaking from hypoglycemia), so it seems CEO Scott Verner is bringing innovation to what had largely become a commodity market.  The Orlando Sun-Sentinel had a fascinating article about some of the things Nipro has done under Mr. Verner's leadership (see the article at http://ow.ly/sbqVu) which you might want to have a look at.

Beyond this, 2013 brought several other changes.

Without question, the Affordable Care Act (a.k.a. "Obamacare") will profoundly impact people with diabetes in 2014, and ways that have yet to be appreciated.  While some segments of the population and the media outlets that cater to those viewpoints have been only too quick to declare it a failure before it began, the reality is this law was the first fundamental change to overtly discriminatory practices which enabled healthcare insurance companies to basically cherry-pick the youngest and most healthy individuals, while simultaneously enabling them to refuse to sell (at any price) policies to people with so-called pre-existing conditions (a list so long that virtually any ailment renders a person ineligible and can therefore be excluded from the market; this incidentally, is one of the law's most popular provisions).  To be sure, there are parts of this enormous reform legislation that will undoubtedly need to be retooled, but the impact will be that the U.S. could possibly climb in the rankings to be closer to other advanced, industrialized societies, whereas the U.S. ranks lower than most in spite of our spending more on a per capita basis (catch my 2008 post HERE for details).

Medtronic Low Glucose Suspend Feature FINALLY Approved by FDA

Aside from that, we saw some long-overdue progress in some areas of treatment, although certainly not as soon as we should have.  Most notably, the Medtronic Low Glucose Suspend feature (in the Medtronic 530G/Veo) finally received FDA approval after Europeans and Australians (even Brazilians) have had access for years already.  Less discussed was the fact that the FDA's approval happened due in no small part to patient involvement and activism.  JDRF led the charge for this particular issue, and it was ultimately our patient testimonies and letters that convinced the FDA why this feature was so badly needed.

FDA Is Realizing that Patient Involvement Here To Stay

Patient involvement, led by patient groups including the JDRF, Diabetes Advocates and Diabetes Hands Foundation and several others has fundamentally changed how the FDA does business.  Although the FDA is required by law to consider input from the American public (which includes everyone, not just doctors and industry), in practice, patients have seldom had direct representation.  But a number of years ago (catch my push in 2010 HERE for more), I started urging patients to participate on accuracy, and I believe the FDA was a bit overwhelmed with how many patients submitted comments.  Since then, patients have pushed the agenda.  To be sure, another branch of the U.S. Government, specifically Medicare, in a move that got little public attention until it was implemented, has simultaneously managed to undermine this with its so-called competitive bidding (see my post HERE) process for mail orders.

However, my friend Bennet [http://www.ydmv.net/] has really done a lot more in that regardthan I have in recent years, with a campaign called StripSafely [http://www.stripsafely.com/] which has pushed the message home to the FDA that accuracy is important.  He has also attended several FDA meetings during the past year, putting a patient face and perspective on meetings that were once routinely regarded as "industry only" meetings.  The team at Close Concerns called attention to the fact that the FDA will hold a series of 20 patient meetings (effectively meeting with patients to discuss their concerns) for a number of different disease areas, yet miraculously, diabetes did not make the initial list of 16 planned meetings, which means there are only four meetings have not been determined, and diabetes should be on the list.  Why the FDA chose to effectively ignore the voices of one of the largest patient groups in the U.S. is unclear, but Close Concerns has a petition to encourage the FDA to put diabetes on the agenda with a Patient Conference for this group of diseases (see their writeup at http://ow.ly/sbrch).  People with diabetes are viewed by regulators and industry as pioneers in this regard, but other groups, including those with autoimmune rhematoid arthritis (RA) which differs from osteoarthritis common in the elderly, have seen what people with diabetes have accomplished and are following our lead to some extent.  In the future, there's a possibility of collaborating with them on issues that impacts both diseases on issues that affect us both, ranging from FDA guidance on biosimilars, to NIH funding.

Anyway, this is my list of some pretty noteworthy events in the diabetes care front for 2013.  I think there are positive signs for 2014, but patients and their caregivers cannot become complacent.  We have only begun to make our presence known with entities such as the FDA, but there are other areas (I'm thinking of the NIH's NIDDK which does not even have a permanent representative it sends to the NIH Autoimmune Diseases Coordinating Committee (ADCC), see http://1.usa.gov/1amQmtQ for more background.

Hello?

The Special Diabetes Program spends billions on type 1 research, yet the NIDDK doesn't have a permanent representative on a committee that could help?!  Yes, that's an area that needs attention, too.  I'm putting it on my New Years Resolutions list.  Maybe we can change that, too!

Thursday, November 14, 2013

On World Diabetes Day, A Tribute to Mary Hunt

The diabetes community lost another member recently.  I knew her as Mary Hunt, and she died at age 66.  She had been hospitalized for illness recently, so her passing was not a complete surprise to her family, but its always sad when we lose someone of any age.  Her husband Dave shared the news via email the other day.  In many ways, Mary was one of the developers of today's Diabetes Online Community.  She helped start the Diabetics International Foundation [http://members.tripod.com/diabetics_world/], which worked tirelessly for the many patients who suffered hypoglycemia unawareness attributed to biosynthetic insulin (an adverse effect the drug industry would prefer no one knew about, and has worked tirelessly to silence, although organizations such as The Insulin Dependent Diabetes Trust have made that impossible), helping to establish processes with the U.S. Food and Drug Administration to enable patients to import natural insulin varieties from the UK and Argentina.

On this World Diabetes Day, I am sharing Mary's obituary (see http://goo.gl/Y7LMRQ).  I am saddened by Mary's passing, but eternally grateful to her for the work she did over the years to help others, as well as her kindness of spirit.  Much of what she did helped me in the work I've tried to do with Diabetes Advocates with the FDA, and I believe patients with diabetes will remain an important constituency for the FDA to consider.  On the latter note, please consider signing a petition to the FDA to sponsor a Patient Meeting on Diabetes (they have only 2 spaces remaining, but somehow aren't convinced a meeting dedicated to diabetes is necessary).  Visit http://diatribe.org/petition to sign the petition.

Without getting too far off-topic, below is Mary's obiturary:

Mary Sebastian-Hunt

Mary Sebastian-Hunt
Mary Sebastian-Hunt, 66 of Clinton, Michigan passed away peacefully Saturday November 9, 2013 at Saint Joseph Mercy Hospital.  She was born on August 3, 1947 in Pontiac, Michigan to Charles E. and Thelma (Hazelton) Sebastian. On March 24, 1990 she married David L. Hunt, a life-long Clinton resident.

Mary lived in the Lansing and Mason area for many years. She was a gifted artist who loved oil painting and interior design. Mary was also an Outdoors Enthusiast and loved fishing and animal watching. Her greatest passion was helping others, including her help in diabetic research and the start of the Diabetics International Foundation.

Mary is survived by her husband, Dave;  her son, Jim Alexander of Tecumseh;  stepson, Darin L Hunt;  stepdaughter, Kimberly E. Hunt-Murphy;  and her sister Susan Mellentine, of Lehigh Acres, Florida.  In addition to her parents, Mary was preceded in death by her brother, Karl F. Sebastian; and her son, Matthew Scott Alexander.

According to her wishes, Mary has been cremated.  A Celebration of Life Service has been planned for Saturday, November 30 at 11 a.m., to be held at the Clinton United Methodist Church, 10990 Tecumseh Clinton Rd, Clinton, MI 49236.  Phone: (517) 456-4972.   A luncheon will follow at the church.

Memorial contributions may be made in Mary's honor to the Clinton United Methodist Church.

Condolences may be offered to the family at http://www.handlerfuneralhomes.com.

Friday, November 08, 2013

Should Have Known Better ...

One would think I should have learned my lessons over the years in maneuvering through the byzantine world of American healthcare delivery (trust me, its not a SYSTEM, folks, but a world where every party involved tries to skim a little extra profit off the ridiculously high premiums Americans already pay), but I routinely find out that's not the case.

Over the years, I have shared stories of how I had like 4 different healthcare plans over the past six years yet have been with my employer for the past fifteen, and it wasn't because I switched plans in open enrollment because the only choice I had was to be covered or not.  Each change brought new rules, new formularies and new appeals processes.  I switched to United Healthcare a few years ago and compared to Wellpoint/ Anthem, I'd say they've been light years ahead.  Its hard to believe, but I've been the proud owner of a Dexcom for almost a year now, something that wouldn't have been a possibility with my old insurance plan.  There are things about the Dexcom that drive me crazy, but in the grand scheme of things, its been key to a much better night sleep for me and my spouse.  It also helps refine overnight basal dosages and insulin-to-carb ratios, and, the kicker is that there have been no severe hypos while I've been wearing the thing, which alone could be saving the insurance company thousands of dollars (one ambulance call would erase any savings they save by denying me a Dexcom).  Why any insurance company would choose to fight this is beyond me, but I've been glad to enjoy it.

Anyway, a while ago, United Healthcare switched me from Medco (which was acquired by Express Scripts anyway) to a Pharmacy Benefits Management company they acquired known as OptumRx.  For the most part, the transition (for me) was seamless, but OptumRx isn't the greatest, and they are moderately better than Caremark ever was.  Over the years, I had stockpiled a bunch of lisinopril when using cheap mail order pharmacies like Walmart (in the days I had an ultra-high deductible plan of $2,500 for me and only me, nothing was covered until I met that threshold, so I found cheap places to get some prescriptions and order there), which is a small-molecule ACE inhibitor whose primary purpose is hypertension (which fortunately, I've never had), although they are prescribed off-label because studies have shown they can have a prophylactic effect on kidney issues common in people with long-term diabetes.  I use a very cheap generic called lisinopril at the lowest dosage, and it's worked damn well because my kidneys seem to be working great after a urine test over a decade ago showed trace elements of protein which is supposed to be a very early warning sign of kidney disease.

Anyway, my stockpile has been running down and I thought I should refill, but I learned firsthand of the profiteering that goes on in the generics business.  As I know for a fact, even without insurance, I could get lisinopril for $10 for a 90-day supply just by ordering from CVS Pharmacy, Target pharmacy, Walgreens or Walmart pharmacy.  So I wrote to United Healthcare and OptumRx (I addressed my letter to the CEO's office; in my experience, its much faster to go from the top down rather than the bottom up), and said I would transfer the prescription to another pharmacy if they weren't willing or able to match the co-pay amount of $10 (OptumRx charges $25, and supposedly United Healthcare is picking up a portion of the total amount, so the unknowing patient is being screwed deep and hard here) - without having to submit a claim to United Healthcare at all, so why the hell would I agree to pay 150% more for a drug that can be bought without insurance for next to nothing?  That makes no sense.  I guess that's what is supposed to happen with healthcare insurance, but it seems stupid to me.

I got a strange response that looks pretty much like a denial, but its so poorly written I can't be certain.  But I decided I won't bother appealing it.  I just called Walmart's mail order pharmacy and the woman on the phone couldn't have been more helpful.  I told her I wanted to transfer my prescription from OptumRx to Walmart's mail order pharmacy and asked her what I needed to do or provide her.  I gave her the Rx number, the name of the medicine, the quantity, strength and the doctor's name, phone number and his fax.  They do the rest.  And, I'm getting this medicine for $10 instead of $25, mailed to me.

I should have known better and just sent it there in the first place!  Note to self: make it easier on yourself next time and do it that way, Scott!

Monday, October 07, 2013

Americans and The Affordable Care Act

Its little secret that the Patient Protection and Affordable Care Act is controversial, although dozens studies and surveys show unequivocally that Americans aren't so much opposed to the law, rather, most have mixed feelings on the law.  Further analysis shows many of those mixed feelings can be attributed to the fact that so few Americans truly understand the law, and the reasons are because of the messaging lawmakers (most notably opponents) have used to describe the legislation.  Also, supporters of the law have done a downright terrible job countering depictions of American opposition as somehow being the common opinion of this law.

If you think back to similar efforts to try and reform the byzantine healthcare industry in the U.S., most notably the 1993 Clinton healthcare plan (known officially as the Health Security Act), a reform package proposed by the Clinton administration, but was more closely associated with the chair of the task force devising that plan, then-First Lady of the U.S., Hillary Clinton, and you see clues as to why efforts to reform the U.S. healthcare "system" (a term I personally use very loosely, because U.S. healthcare is less of a coordinated system than it is a group of entities trying to skim a profit off the illnesses of others) have struggled to win favorable public opinion.  That also explains why the Patient Protection and Affordable Care Act ("Obamacare") has has such mixed opinions.  But the Clinton plan was never implemented, and importantly, the Affordable Care Act's supporters learned a few things from that experience when they tried again in 2010, sewing the seeds to the latest last-ditch efforts by the losers to get their way one last time.

The British magazine The Economist recently featured a chart on this important law (and it IS U.S. law; it went all the way to the U.S. Supreme Court and was upheld there as lawful).  The Economist notes that new computer analysis (see HERE) counts the GOP policy ideas that overlap with other bills that made it into the law: 3% from the House and 8% from the Senate. In fact, when "mark-up" bills are excluded — basically, amendments and legislative re-writes—11% and 28% of policy ideas from Congressional and Senate Republicans, respectively, align.  John Wilkerson of the University of Washington and his colleagues studied the legislative history using big data. They ran the PPACA through a text-analysis system that could spot similar wording in previous legislation with a better than 90% accuracy. That let them identify the date and sponsor of earlier bills that ended up in the law, indicated as circles in the chart. Hence, proposals by Republican Senator Chuck Grassley of Iowa on nursing home transparency in March 2009 were incorporated by Democratic lawmakers in later bills, before appearing in the law.

Hence, The Economist notes that on the surface, Obamacare looks totally partisan, largely because not a single Republican voted in favor of the legislation when it was still a bill.  However, the analysis shows that the law is filled with a lot of concessions to Republican opponents, which helps explain why many continue to oppose this law like sore losers: much of this law uses Republican ideas, making their defeat on this even more humiliating.  Add to that a stunning defeat by the Supreme Court, and you have the recipe for ridiculous Congressional theatrics like Texas Senator Ted Cruz's recent non-filibuster (it can only be considered a filibuster when legislation is actually pending a vote).

When researchers look into it, the reality is that the American public loves much of what's in Obamacare.  For example, the Los Angeles Times recently ran a fascinating article entitled "The truth is, Americans love Obamacare" (see http://lat.ms/19eIA9J).  While the title of that article is misleading (in my opinion), the author reports that research from the nonpartisan Kaiser Family Foundation tracking research from March 2013 showed (see that study at http://bit.ly/18BQtAx) the following:
  • 88% of Americans are in favor of extending tax credits to small businesses in order to buy insurance for their employees
  • 81% of Americans favor closing the Medicare drug benefit doughnut hole
  • 75% of Americans favor extending dependent coverage to children up to age 26
  • 71% of Americans are in favor of expanding Medicaid
  • 66% of Americans favor banning exclusions for preexisting conditions (although when you actually tell someone what qualifies as a preexisting condition, other surveys show that more like 75% favor this)
Yet when respondents are asked how they feel about "Obamacare," they're overwhelmingly against it.

Still other research shows shows some big demographic differences.  For example, Americans in the 18-29 age group are the most likely to be uninsured (22%) also, perhaps not surprisingly respond most favorably to Obamacare, with 51% opting to keep it. By contrast, Americans age 65 and older are the least likely to be uninsured because they're collecting Medicare (3%) are also the most likely to object to Obamacare, with only 32% electing to keep it.  These results are from a recent Bankrate survey on the topic which can be viewed at http://prn.to/1bCtdtt.  There are other studies which show that Hispanics, another group less likely to receive employer insurance coverage, also like the law.  Simply stated, Americans' views of the law varies considerably depending on how it is described, and whether a person is insured already or not.

With that in mind, consider the following:

First, The Affordable Care Act now the law of the land, so disregard suggestions (and Congressional theatrics) to try and defund it.  That train left the station several years ago, and some are sore losers about it.  However, my readers may recall that on September 24, 2013, I Tweeted a Bloomberg article by Paula E. Dwyer entitled "Five Republican myths on defunding Obamacare" (see the article at http://bloom.bg/16EYMuL).  Myth No. 1 was that shutting down the government would somehow stop the healthcare law from taking effect.  As it turns out, most of the health law's funds come from the entitlement programs Medicare and Medicaid, which don't need Congress's annual blessing, so a shutdown would do almost nothing to "defund" the law because the funds for Obamacare aren't even subject to Congressional debate.

The reality is that in spite of technical issues, the marketplaces were opened, and the government reported that within 24 hours of its 12:01 a.m. launch, the Department of Health and Human Services' health-care website (http://www.healthcare.gov/) had received 4.7 million unique visitors. By the end of Day Two, the number was greater than 7 million. (HHS has not yet released the number of those who have actually signed up for coverage.)  By week's end, demand was still so great the website, HealthCare.gov, remained difficult at times to get into, despite the addition of more computer servers.

Second, if you're someone with a chronic medical condition like diabetes, you are a major beneficiary of this law.  You can now buy healthcare insurance whereas in the past you weren't even permitted to buy insurance at any price except in states which had laws prohibiting insurance companies from doing so.  As it turns out, such laws also significantly increased the costs of plans in those states, but those same states also saw the smallest increases or even decreases after "Obamacare".  Discussions about the cost have generally ignored this not so little fact; many people can now buy insurance who were discriminated against in the past, a major, major factor in the reasons why rates for many were so low in the past.  Now, if you have diabetes, you CAN buy healthcare insurance, whereas in the past, you were out of luck.  Is that how free markets are supposed to work?

Indeed, several states including California, Colorado and Connecticut which are running their own exchanges have reported significant interest.  Connecticut, for example, reported that the number of of people looking into healthcare plans online or by telephone was far more than Access Health CT CEO Kevin Counihan had anticipated.  There were even reports from HHS that in states like Kansas which have deferred all Obamacare administration to the Federal government, also had high consumer interest in Obamacare.  Opponents claim they will see a different picture when the bill for Obamacare come due, neglecting the fact that in the U.S. today, bankruptcies resulting from unpaid medical bills are forecast to affect nearly 2 million people this year—making health care the No. 1 cause of such filings, and outpacing bankruptcies due to credit-card bills or unpaid mortgages, according to data derived from the U.S. Census, Centers for Disease Control, the federal court system and the Commonwealth Fund and crunched by NerdWallet Health.  That suggests that the cost of insurance is more than offset by a single costly hospitalization.

The reality is that the United States is the only advanced, industrialized economy that did not offer universal healthcare until the Affordable Care Act became law, and while there will be refinements that can be made over time, yet nearly 6 in 10 Americans disapprove of trying to stop the law by cutting its financing.  Besides, Congress has already funded it, and the chance to defund it ended in 2012.  Lawmakers who are opposed lost their opportunity to do this over a year ago.

Even among those Americans who don't especially like the law, less than half want their representatives in Congress to try to make it fail.  The reasoning seems to be it was passed into law by legitimate means (indeed, the Republican party itself had used the same Congressional procedure in the past), and it addresses a legitimate U.S. need, so they want to see it have a chance.  Since the repealers have suggested no alternatives other than to kill this law, they have failed on several levels.  Most Americans want to see how things end up working with Obamacare, and expect their lawmakers to do the same.

Author P.S., October 30, 2013:  Its not really a secret, we've known that once the Affordable Care Act was implemented, substandard insurance plans would be replaced with better, stronger coverage.  That also means that the really low-cost healthcare plans are likely to disappear, although such plans are insurance in name only.  Bare-bones insurance coverage tends to cover only outpatient hospitalizations, and they don't typically cover ambulance service or even basic prenatal care.  The so-called benefits that such plans actually do provide may include generic drugs (many of which can be attained from major pharmacies for as little as $10 for a 90-day supply without insurance), and certain doctors' appointments are covered with a $50 co-pay.  The price for such an "insurance" plan: $54 per month, which is low by almost any definition, although certain media outlets are describing the fact that the individuals impacted cannot afford more.  The Washington Post recently reported one example (see http://wapo.st/1aPebdz for the article) that Fox news highlighted.  However, the bare-bones plans which are disappearing and are really better described as a "pray-that-you-don't-really-get-sick 'plans'" because those plans (if they even deserve the description of insurance at all) don't cover cover much of anything.  The example cited failed to cover “extended hospital stays" whereas hospitalization is among the core requirements for health-care plans under Obamacare.  As the Rachel Maddow show described it (see http://on.msnbc.com/1g9gteR), "In other words, the new horror story for critics of the health care law features a middle-aged woman trading a bad plan for a good plan, and health care insecurity for health care security."  Many of the sensationalized stories of complaints (highlighted by Fox News) by people who are seeing their monthly costs jump under the new Obamacare plans are conveniently omitting the fact that many people including the woman featured in the Fox News story, will actually be eligible for subsidies under the Affordable Care Act, hence the cost of the coverage being reported isn't what these so-called "victims" of Obamacare will actually have to pay out of their own pockets.