WHAT SHOULD CANCER DRUGS COST?

Toasty warm in
Glacier Bay, Alaska, 1991  

It has become painfully obvious that many, if not most, of you skim my laboriously crafted blogs searching for amusing bits of trivia and avoiding anything at all technical.  Several of you have confessed as much, and I suspect the prevalence of this behavior in a large part of my “audience”.  (This is in addition to the hundreds of pseudo-“hits” generated by computer algorithms from Latvia, Poland, Russia, etc. searching for who know what.)   In fact, I suspect that many of you are simply going to “Myrl’sBlog” to see a picture of Linda, and have no Intention of reading anything;.  You disappoint me, but I will carry on.  This next blog is about cancer, all right, but not about biology, and you should read it.  It is about money

Would you ever have guessed that of the 12 new cancer drugs approved by the FDA in 2011, 11 of them cost more than $100.000/year?  And that old people on Medicare would be out-of-pocket $20,000 to $30,000 to take them?  And that all of them can be shown to be “successful”, defined as buying the patient a few more months of life?   These shocking facts are brought to you courtesy of Linda’s sister, Carolyn.  You can read about them yourself by going to the following web address:

http://health.yahoo.net/experts/dayinhealth/cancer-doctors-protest-astronomical-drug-costs

Obviously drugs are going to cost real money.  Companies making them must cover the cost of research, including research to develop new drugs that don’t pan out.  And, to stay in business, they must show a profit. I accept all that.  The problem seems to be that the usual price-setting role of competition doesn’t apply here, given the way the drug industry is structured. Getting a new drug to market goes something like this.  First, some smart and/or lucky biochemist (more likely a group of such) runs on some aspect of cancer development that they think they might be able to exploit.  Then they spend years trying to determine whether it actually works. If it seems to work, they sell it to Merck or Novartis - that is to big pharma.  Then big pharma studies it some more, for years sometimes.  Very likely, it doesn’t work - and Merck or Novartis is out a bundle of cash.  “Finding out” normally will involve one or more extremely expensive clinical trials.  If the drug does seem to work, the company asks the FDA to approve it for clinical use.  The FDA takes God’s own time making that determination, and often as not it's decision is “no”.  But suppose it’s “yes”.  In that case Merck or Novartis ponders on its costs and arbitrarily sets a price. Note that neither the FDA nor market forces have any say in the matter. And so, the drug goes on the market. 

Clearly, if this were a market for shoes, or whiskey, competition would determine the price.  If your drug did something that some other drug does better, you would have to sell it for less.  But that’s not the way it works here.  For one thing, Medicare (and supplement insurance schemes) are required to cover the drug, even though it is ineffective or over-priced.  And some “clinicians” will prescribe it because “it’s new, and thus must be better” Or, patients actually believe the noxious drug commercials that run on TV all the time, and they ask for it.  You must agree: this is a stupid way to run a health care system.

What to do?  Well, oncologists at two of the foremost cancer hospitals in the country are refusing to prescribe some of these expensive drugs even, I guess, if the patient demands them.  Good for them.  Also, it has been suggested that Medicare be allowed to bargain with big pharma and extort “bargain” prices.  The VA does this and can supply drugs to sick veterans at half the cost Medicare charges.  Again, drug X in, say, Canada or the UK (“Socialized Medicine”!)sometimes costs half what drug X will set you back in the U.S.  So, something is definitely rotten in Denmark or, in this case, the U.S..

So, let’s think about a solution:

Maybe all drug research should be done by non-profits, or by the government. I know some of you believe strongly that this would work, but after 80 years of dealing with government, including government science at all levels, I much doubt it.

Figure out some way to get competition into the drug pricing business.  Sounds great – but, how?  Mom and Pop drug firms are never going to happen.

So, this free market, small government conservative is driven to the wall.  I’m afraid that we need the FDA, or some other agency to set prices.  I hate the idea, not least because it will bring politics into the drug business, with possible desperate consequences.  If prices are set too low, to please the consumer (aka, the voter), there will be no incentive to develop new drugs(profit incentive, that is – there is little altruism in big pharm, or anywhere else).  If the prices are set too high, to encourage research and development, patients will be unable to afford the drugs. 

Okay – there was no biology at all in this blog, so you have no excuse not to have read it.  What do you think?  I will be counting the Comments.

        

  



PROFILES IN RESEARCH EXCELLENCE 4: Dr. Ilona Kryczek

Linda as a new Physical Therapist

 

They were lucky to have her.

 

Dr. Ilena Kryczek is an Assistant Professor with the University of Michigan medical school.  She received a Pilot Study grant from the Marsha Rivkin Center in 2008.  She works in the extraordinarily active cancer research lab of Weiping Zou, who is well known and highly regarded in the cancer research community.    As part of that team Dr. Kryczek has been a co-author of over 50 publications since 2004; for four of these she acknowledges the support of MRC.  Her principal area of interest seems to involve the study of gene Th17, which codes for a molecule called Il-17+.  This seems to be a kind of leucocyte, called a T helper cell, that is involved in the autoimmune reaction   Apparently there is good reason to suppose that, if properly assisted, teased  and stimulated, Th17 can mount an immune response to cancer.  Let it be true! 

Dr Kryczek was born and educated in Poland and practiced there before transferring her efforts to the United States.  As the result of her work, partially supported by MRC, she has recently been promoted within the University of Michigan faculty.  Despite her productive and no doubt time consuming activities in science, Dr. Kryczek has found time to raise a family – including at least one young boy, if Google Illustrations can be trusted.

Finally, a person in a position to know says that “Ilona Kryczek is one smart cookie.”  I hope I didn’t garble her science too much.  Maybe she can write a Comment and set me straight.



OC STATISTICS. And an announcement

Linda at one.

cute as a bug's ear

I post this picture to announce that I will be a great grandfather, twice over, by Thanksgiving.  And that’s all I’m going to tell you. 

There has not been a boy born into the Beck family since 1933.  What are the odds?

I am at Fred Hutch today, reading.  One thing I have read is a study of ovarian cancer incidence and mortality, world-wide, using data from various sources covering the interval 1988 to 1998.  Unlike most of the research papers I attempt to read, this one is blessedly free of undefined acronyms (although there are a few), and terms that only a Ph.D. oncological geneticist could appreciate.  You can read it yourself by using Google Scholar and searching for the following pub: Lowe, et al¸ 2013, An international assessment of ovarian cancer incidence and mortality, Gynecologic Oncology, as yet unpublished, I guess, so I can’t give you the volume and page numbers.  But don’t bother: I will fill you in:

Things are getting better, but very slowly.  There are fractionally (small fractionally) fewer cases of ovarian cancer diagnosed each year**, and comparably fewer deaths.  World-wide it is estimated that 225,500 women were diagnosed with ovarian cancer in 2008, and 140,000 died.  The lifetime risk of developing ovarian cancer is <2% for the general population.  However, if there is one family member with OC, the risk is 4-5%, rising to `7% for women with two family member with the disease.  Notably, the lifetime risk for women who carry the BRCA1 or BRCA2 mutations, the risk is a whopping 30%.  To me, the moral here is: If you can afford it, get tested.

I want to emphasize that, although things are getting better, the statistics are still dismal.  We need to keep plugging away.

Curiously, there are significant differences between races and regions – and, for once, white people living in Europe and North America don’t make out so well.  Having an advanced economy also doesn’t seem to help, either.  For instance, within the Americas, the five-year incidence of ovarian cancer is twice as high in the United States and Canada as it is in Brazil and Mexico.  Asian countries (except, curiously, Japan) have rates only a third as high as the United States.  Our rates are comparable to all European countries, except Portugal, which is very low.  (Is it all the octopi they eat?). 

As for race, Caucasians have significantly higher rates than do all other races, both worldwide and within the U.S. 

So, what does this mean?  It may represent something genetic, and (I would guess) to some extent it does.  Is it an artifact of the medical system - that is, are women in Europe, Canada and the U.S. more likely to get a timely,  correct diagnosis*?  Or is it that Caucasian women in rich countries subject themselves or are subjected to more of the things known to be associated with risk of ovarian cancer, which I will list below?  Damned if I know. 

The list:

                Obesity

                Hormonal exposure

                High number of ovulatory years

                Exposure to radiation

                Smoking, caffeine consumption, alcohol consumption

                A diet high in lactose

                Frequent hair dying

                Use of antidepressants

                Asbestos exposure

                Use of talc in genital area

                Endometriosis or pelvic inflammatory disease

               

Note that the authors of this paper appear ambivalent about the connection between all of these and ovarian cancer.  My take on it is that you can’t avoid everything potentially unhealthy.   Just try to avoid the ones that aren’t fun.

*To test this it might have been relevant to include statistics from Cuba.

** This is in percent of all women.  Naturally, as population increases there are more cases of ovarian cancer diagnosed - but a smaller percent of the total.



EPIGENETICS, Chaper 2

 

 

With Amanda

 The first grand-child gets the most pictures

 

 

For mid-April this is a spectacularly rotten day, even for Bellingham.  A few minutes ago it was snowing hard; my deck has accumulated a substantial layer of nasty slush.  I know this will seem as nothing to you folks in Kalamazoo and points north and east, but for here it is unusual.  One thing is for sure; the weather has “dampened” my enthusiasm for gardening.  I planted my potatoes, onions and leeks a few days ago, during a four-hour sunny spell.  Now I am hunkered down inside, studying – epigenetics.

I wish Joanne, David, Olivia, Amanda, or anybody else at who is at home in the murky world of biology would ease my pain and explain epigenetics to me, in terms an elderly geologist can comprehend.  If you followed the link in my last blog you may have noticed a link to epigenetics.  Brashly, I clicked on it.  The resulting flood of information promises to keep me inside and out of trouble for a long time.  The  Time link to epigenetics yielded an 8-page article that I can almost understand.  It talks of something called “epigenetic marks”, left mostly unexplained.  Googling that term in turn yielded a Wikipedia article 16 pages long – which cites 138 references!  In despair I just ordered a book on epigenetics, using the Abe Books web site.  It won’t get here for a few weeks, so I have an excuse for sidestepping epigenetics and cancer for a while.  Here is the current state of my ignorance. 

Be warned.  What follows is pure biology, probably misleading, and indubitably boring.  Quit now and enjoy the picture.

“Epigenetics” in this context refers to factors that control gene expression.  Every cell in your body has the same DNA; that is, they all have the blueprint for everything from teeth to toenails to testicles.  Yet you do not grow teeth in your toenails.  This is because these things called epigenetic “marks” control which parts of your DNA – which genes – are “expressed”; that is, used to make proteins.  In your toenail cells the genes to make teeth are turned off by the appropriate epigenetic markers.   Epigenetic markers work biochemically in a number of mind-numbing ways – the most frequently mentioned is “methylation”, which involves plopping a “methyl group” at a crucial spot on the genome.  Apparently this prevents the gene from being expressed.  Epigenetic markers can be influenced by the environment.  To make up an example, if you are starving to death, markers may be manipulated so as to slow down your metabolism and start burning stored fat.  When food becomes available these markers cease to operate and the markers for happy gluttony kick in.  This much I almost understand.  What I cannot fathom is HOW IN HELL CAN THESE THINGS BE INHERITED?   To be Inherited doesn’t a thing have to be coded for in the DNA?  Experiments demonstrate that inheritance does occur –see, for instance, my blog GRANDMAS CURSE.  But how?  I will attack the subject by & by, after the book arrives, but now I’m going to watch the Masters on TV.

The snow has stopped.  



DREAM TEAMS

Linda in her tiny apartment during PT school

The plaque on the wall probably read "Be of good courage: all this will soon be over"

Time magazine recently feature an article about the “Dream Team” approach to cancer research.  The topic of the article is something called SU2C, short for “Stand Up to Cancer”.  Apparently it is the brain child of several Hollywood celebs, somel of whom have personal experience of cancer.  SU2C employs a team approach to cancer research.  To quote the article, “attack cancer the way you make a movie: bring the most talented people together, fund them generously, oversee their progress rigorously, and shoot for big payoffs – on a tight schedule”   This is contrasted with research conducted by “narrowly focused investigators beavering away, one small grant at a time”.  Apparently ten groups have signed on to the SU2C approach, including the very well regarded MD Anderson Cancer Center. 

Dream Teams comprise “geneticists, pathologists, biostatisticians, biochemists, informaticists*, oncologists, surgeons and technicians”, all working together on a common problem. 

Sounds good, but I forsee problems.  For one thing, coordinating actions of such a disparate group is bound to be complicated.  Big egos, as well as big talents, will be involved.  I foresee battles over budgets, precedence, authorship, and even office space: who gets the corner lab with the big windows?  And, of course, nobody ever gave a Nobel Prize to a committee.  Also, this sounds a bit like the “War on Cancer” declared during the Nixon administration.  It was to be a team effort, lavishly funded, and its declared purpose was to rid the world of cancer, once and for all.  As we know all too well, it failed.  What it did do was to demonstrate just how complicated cancer is, and that a multi-pronged approach to the problem was essential.  Thus, I am hopeful for progress under the team approach, but I hope there will continue to be support for the lone scientist beavering away on some interesting problem of basic cancer biology. 

One thing about the team approach I really like: teams will be judged by patient outcomes, not by the number of papers published.

One of the approaches to be taken by these teams is “epigenetics”.  I have written about this before, with mystification.  The Time article gives a link to epigenetics which I may be able to understand.  If I do, I will let you know.

If you want to read the article yourself, the link is http://healthland.time.com/2013/03/21/cancer-dream-teams-road-to-a-cure/.

This blog was brought to you courtesy of Linda’s sister Carolyn, who has joined my army of poorly paid (but greatly appreciated) research assistants.

*I don’t know what these people do, either.  I Googled it, read several explanations – and I still don’t understand.  But I'm sure they do good work.



INCREMENTAL PROGRESS

Mountaineering expedition to Artist's Point

 

Judging from the beard, the late 1980s

 

 

I am home now, in Bellingham.  I spent several enjoyable days with Carolyn, Linda’s sister in Eureka, California.  Eureka is a beautiful place, with all sorts of outdoor recreational activities, ranging from salt water to mountain peaks.  I urge any of you thinking of moving to Bellingham to try Eureka first.  Housing is cheaper in Eureka, the climate is no worse.   There is a world-class used bookstore there, as well as several world-class dives**.  Besides, Bellingham is too big already.  I spent a full three minutes trying to turn left a short time ago.  That would never have happened 30 years ago; hell, we didn’t even bother to look when we turned left in those days.  The main streets were cobblestone, with grass growing between the cobbles.  Well, that’s the way I remember it, anyway.

About a year ago I wrote a blog comparing the IRS to the Inquisition.  I have no energy to rail against them this year; the tax code has beaten me into submission.  I got quite a bit of money back last year.  This year I am giving it all back.  Plus a fine.

I want to write about some research brought to my attention by Joan McManus (she is the in other lady in the picture accompanying my blog for January 31^st;  thanks you, Joan).  She sent me a clipping from the LA Times, containing an article entitled “Study links new DNA regions to 3 cancers.  The three cancers are breast, ovarian and prostate.  It appears that a colossal international study has been going on for some time.  It is called the Collaborative Oncological Gene-environment Study, or COGS.  The study involved roughly 250,000 people and enough scientists to publish 13 papers simultaneously (last week),  in four different journals*.  The results seem to offer hope of early detection in some cases, as well as – I hope – increased insight into the cancer problem as a whole.  More specific I cannot be: I found an article in Nature Genetics purporting to explain the work to the biologically challenged; I didn’t really understand it.  Suffice it to say that there are things called SNPs, which stands for single nucleotide polymorphisms.  These are point changes in the DNA sequence:  an A where a T should be, for instance.  If the T causes the protein “coded for” by the gene in question to fold wrong and thus assume the wrong shape, all sorts of havoc may ensue.  They found three regions where SNPs influence the likelihood of contracting ovarian cancer.  I hope they are scrutinizing these regions very closely.

That’s almost enough biology.  However, I am going to introduce a new feature to this blog.  I guess you could call it “Biology Vocabulary Builder”.  In it I will share with you what I learned from – mainly – Wikipedia.  You will be fascinated.  So here goes:

        Pleiotrophy.  This is the case when a single gene affects more than one phenotype.  Thus, to invent an example, gene HTn might be necessary to grow hair, and but also contributes to rotten teeth.  Thus, you might “knock out” HTn to improve dental health, but create a race of bald people.  As you might guess there is a bit more to it than this, but this probably is more than enough.

*Studies like these would be impossible in geology.  Geologists instinctively distrust the motives of anybody messing around in their particular research area, hence large cooperative investigations almost never happen.  Partly this is the result of the cut-throat competition for funding, but mainly it is because geologists tend to be misanthropic loners.  To be honest that’s not actually true – except much of the time. 

** It also is the pot capital of North America.