A sobering assessment from the recent World Oncology Forum on the potential and results from some of the new targeted and personalized drugs. Quote:
Only a few years ago, many cancer experts thought the arrival of targeted medicines, designed to attack the genetic makeup of the tumour, would make dramatic inroads into cancer deaths. That has not happened. Instead, these therapies have only bought a few extra months of life. If the question was whether the world was winning the war on cancer, said Douglas Hanahan of the Swiss Institute for Experimental Cancer Research, who outlined the latest state of drug research, “in general, for most forms of human cancer, the answer is clearly no”.
The excitement generated by targeted drugs, which interfere with specific molecules involved in tumour growth and suppression, has been short-lived.
Linked to this are some of the perverse industry incentives, the high cost of some of the new drugs, and the need for greater emphasis on prevention.
Cancer fight stalls amid push for profits, doctors say | Society | The Guardian.
Further to the op-ed by Memorial Sloan-Kettering oncologists (A Hospital Says ‘No’ to an $11,000-a-Month Cancer Drug), more on how cost considerations are increasingly playing a role in deciding which drugs to use, and the requirement for better outcomes and benefits to justify additional cost. Quote:
The Ben Goldacres of the world will claim that biopharmaceutical companies run minimal clinical trials to get drugs approved. That might have been the case years ago, but that’s not acceptable now. Physicians, payers and even patients are demanding that the expensive drugs that are prescribed deliver value. Sanofi and Regeneron are feeling that pressure today – as will others who can’t demonstrate the value of their new drug over existing treatments. The MSKCC oncologists may have drawn a line in the sand, but this line has been years in the making
Cost Matters Not Just in Cancer Care But In Other Diseases Too – Forbes.
A good piece by Memorial Sloan-Kettering oncologists on intelligent and appropriate cost considerations in medication use and choice, and when not to use more expensive treatments. What I find interesting is that both drugs mentioned, the cheaper Avastin and the twice as high Zaltrap only prolong life by an average of 1.4 months, not years. Quite frankly, hard for me to see much benefit in either drug. Quote:
Once you take all this into account it may seem surprising that the decision to exclude Zaltrap from our hospital’s formulary was a hard one to make. But because our medical culture equates “new” with “better” so unequivocally, a decision like this one can seem out of place at a leading cancer hospital
Political rhetoric today is similarly slanted. Our refusal to adopt this remarkably expensive therapy risks being labeled “rationing,” not rational.
This political climate also helps explain why the Affordable Care Act precludes Medicare from changing its coverage or payment amounts based on cost comparisons like the one we have outlined, even when two drugs appear to work equally well. And it is probably why neither presidential candidate has addressed runaway cancer drug prices.
But if no one else will act, leading cancer centers and other research hospitals should. The future of our health care system, and of cancer care, depends on our using our limited resources wisely.
A Hospital Says ‘No’ to an $11,000-a-Month Cancer Drug – NYTimes.com.
About a month later, Sanofi announced that it was halving the price following the Memorial Sloan-Kettering decision:
Sanofi Halves Price of Cancer Drug Zaltrap
A somewhat lengthy but interesting article contrasting the relative simplicity of aircraft design to modelling biological processes. A sobering reminder of just how complex the human body is, how much we don’t know, and why progress in drug and other treatments remains painfully slow in many cases. Quote:
At first sight there indeed don’t seem to be too many differences between the two processes. Proteins and drugs (which are usually called “small molecules” in the trade) are machines with many moving parts, just like airplanes. They are buffeted by surrounding water molecules in the body just like airplanes are buffeted by airflow. And just like airplanes, their parts are dependent on each other’s motions. Of course, airplane design seems to depend on classical mechanics while drug design would probably need quantum mechanics, but that seems to mainly translate to a question of computational expense. If we can really conceptualize the concerted motion and concomitant functions of tens of thousands of gauges, valves, nuts and bolts, measuring instruments, flaps, wheels and innumerable pieces of metal and plastic in a Boeing 777, what stops us from similarly conceptualizing the interaction of myriad amino acids, water molecules and one small molecule in a test tube?
The answer to this question is something we are still working out, but the short answer is “biological complexity“. Accurate drug design from scratch will only be possible when we can realistically simulate and understand the structure and function of both small molecules and proteins in the body. A few months ago there was an article in a drug design journal by Walter Woltosz from a company called Simulations Plus which tries to model the metabolism of drugs. Woltosz wondered why we are not as good at designing drugs as we are at designing airplanes, and I blogged about his article here. My guess is that while computational drug design is certainly going to get better, I am not holding my breath before it has the predictive power of airplane design. What exactly makes the difference?
Here’s your Boeing 777, now make me the next Prozac. | The Curious Wavefunction, Scientific American Blog Network.
A good in-depth article on how employers are trying to reduce drug costs (in Canada, drug plans are provided by some employers, with government coverage limited, if memory serves me correctly, to seniors and some other vulnerable groups). The market at work in terms of reducing costs, as competition among pharmacies to win employer business heats up.
The battle to bottle up drug costs – The Globe and Mail.
Further to earlier posts (Is Personalized Medicine a Myth and Serious Side Effects More Likely in New Cancer Drugs), a more thorough discussion of the issues for the cognoscenti. Quote:
… it’s important to note that, as incredible and copious as it is, all this genomic data doesn’t help us that much—yet. The reason is that we don’t yet know what to do with this “firehose” of a data stream, how to apply the data contained therein to guiding patient care in order to cure more patients and prolong the survival more of those who cannot be cured. I actually believe that one day we will have the tools and knowledge to do that, such that I envision a day when we will use tumor biopsies and blood to construct comprehensive genomic, transcriptomic, and proteomic profiles of individual patient tumors and use them to target the molecular derangements that drive them. However, I am under no illusion that reaching that day will be easy, cheap, or without other cost. Studies like Niraula et al keep us humble.
New cancer drugs: Fitter, happier, more productive? Or not? – Respectful Insolence.
While the headline is scary, the body of the article is less so. Again, it is all about trade-offs; without the new drugs, patients would die earlier. Quote:
“Overall, at least we can say from clinical trial patients that the benefit (of these drugs) is more than the risks,” said Dr. Shenhong Wu, a cancer doctor from Stony Brook University School of Medicine in New York, who wasn’t involved in the new study.
But patients included in large, pre-approval trials may be healthier, or younger, than most people who are expected to ultimately need the drugs – so whether a drug is worth its possible side effects will depend on each individual patient, he added.
“In the real world, patients are complicated; they have all kinds of issues. So the benefits and risks may be different,” Wu said.
Amir told Reuters Health that when patients and their doctors are discussing starting a new treatment, doctors should take into account a patient’s overall health, and not just the cancer. “I wish there were easier decisions that people with cancer had to make, but most of the drugs are toxic,” [Susan] Ellenberg said.
[Eitan] Amir told Reuters Health the analysis should not be seen as a takedown of cancer drugs.
“These are all drugs which improve outcomes, certainly of cancer, and overall survival,” he said. “The only thing we’re trying to highlight is, it’s not as if you’re getting anything for free.”
Serious side effects more likely in new cancer drugs – Health – Cancer – NBCNews.com.
A good analysis about the ethics and risks of compassionate access to experimental drugs, prompted by the campaign for Darcy Doherty and his unfortunate recent death. Quote:
The sad case has given new urgency to a long-standing, gut-wrenching debate: What obligation, if any, do drug companies have to terminally ill people? Should they help very sick individuals even if that could jeopardize clinical trials and delay the introduction of a drug? What about the testing process over all? Why does it take more than a decade and as much as $1-billion to bring a new drug to market? And should these questions be left in the hands of drug companies in the first placeÉ
This case “is sort of illustrative of the tension that arises during drug development,” said David Hogg, an oncologist at Toronto’s Princess Margaret Hospital specializing in melanoma, who treated Mr. Doherty. “We all want things to go really fast and we all want things to be very safe.” But sometimes you can’t do both.
“I don’t think it’s an issue that’s ever going to be resolved completely,” Dr. Hogg said, “because the objectives of pharmaceutical companies and the objectives of an individual patient are not congruent.”
…. “There’s no bad guy here at all,” Dr. Hogg said. Bristol-Myers, he said, was concerned about accidentally hastening Mr. Doherty’s death, “and there’s the potential of doing that. And Darcy [was] worried about not getting a drug that might prolong his life.”
Ms. Cumming, Mr. Doherty’s wife, knew that she was breaking new ground. “I think this is new territory for everyone and that’s why we are really pushing compassionate access,” she said in an interview before her husband died. “It’s hard to see a drug that you know your husband has a really decent chance of responding to is just outside of your grasp. We are just so close and yet can’t get it.”
The question is whether there’s any way to answer that kind of pain and frustration without putting much more at risk.
Drug trials on trial: Is it really greed versus good? – The Globe and Mail.
A good overview of the issues around increasing drug costs. Some points, largely reflecting uniqueness of US healthcare:
- cost becoming a more important consideration
- reduced acceptance of coupons to reimburse patient co-pays given that other additional costs not covered
- experimentation with different payment systems based upon time with patients, not on drug mark-ups, including higher patient co-payments for therapies with a poor chance of success
- increased use of generic drugs
- analysis of the ‘perverse’ incentive structure (e.g., co-pays for oral vs injection drugs)
To be used consistently, an oncology drug must show a benefit for patients.
“It has got to be meaningful and it has got to be cost-effective,” she [Mace Rothenberg] said.
Analysis: Drug costs become bigger issue in cancer care | Reuters.
In contrast to Cancer Drug Targets: The March of the Lemmings – Forbes, which argues that risk averse drug companies rush to the same ‘next great thing’ and breaks down the 1,000 new cancer medicines by category, this more superficial commentary, almost a puff piece for the pharmaceutical industry, just uses the number of 1,000 to be more encouraging.
Expect the reality is somewhere in between.
And of course the biggest fallacy in the Schoen piece is in his line ‘Future medical advancements are our best hope for lessening the burden of cancer to patients, their families and society’ without one word on prevention, where the biggest improvements in outcomes are possible.
Great Strides Made In Developing New Medicines For Cancer – Forbes.