Prostate cancer drug so effective trial stopped
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Possibly J&J "invented" a novel therapeutic use for the drug and so gained a further patent?
As charities are required to open their accounts in the UK then presumably the amount the licensee paid to Cancer Research UK is part of the public record. It would be interesting to read the terms and the fee involved; presumable Cancer Research would only give an exclusive license for a very generous consideration otherwise they might be in the position of being locking up a useful drug that was paid for by charitable giving and presumably that would be so contrary to their principles.
I wonder if they have an SPC in the UK?
That's the nature of science, no one person ever discovers a drug independently. All new science is build on the basis of old science.
If you wanted to sequence a piece of DNA in the 1980s (an entire genome was laughably out of the question), you would use Sanger's method and get a few hundred base pairs in a month. Maybe an entire gene in 3 months. Now we can sequence whole bacterial genomes or genotype a million SNPs in an afternoon, but gaining new, important knowledge is still much more expensive.
As a general rule.... but it's not like we know it's impossible these days. Who's to say that a lone researcher won't come up with a startling simplification of physics? Maybe this won't ever happen. The point is we don't know, and it's not as certain as what your comment implies.
Peace.
You could have said the same thing in 1900, eight years before the publication of the first paper on general relativity, arguably the most important advance in physics, ever, and something Einstein did independently.
Tthe Einsteins and Maxwells of the world don't come along very often, and the fact that we haven't had one in awhile is more a reflection on that rarity than any characteristic of modern science.
Assuming double blind tests are akin to A/B testing, at what point was the trial stopped? Was it stopped before there was statistical significance?
Or, are there differences in how double blind tests are done than how A/B testing is done in software and websites?
I'm guessing... no. I'm guessing they don't call off a zillion-dollar phase III clinical cancer drug trial without running it by someone who has glanced at an undergrad statistics textbook.
We're not just banging rocks together here, guys, we know how to do clinical trials.
There are many problems with clinical trials. Read Ben Goldacre for examples.
One problem is that good results are published, while bad results (when they're submitted, which isn't often) are too boring for publication.
And then there are all the other problems of studies that aren't correctly blinded, or the selection is faulty, or etc. These are all reputable pharma companies with substantial funds to run tests.
I am, obviously, addressing your comment because there's not nearly enough detail in the article to discuss.
Also, it's very rare for big pharma companies to screw up a clinical trial. It's much more common in the small biotechs and non-profits. If there is one thing that big pharma companies are good at is drug development (not so much drug research).
Yes, and the statisticians in the FDA and the drug companies have a lot of experience in this.
I think they started looking at ways to end trials early back in the ADT (anti-HIV drug) days. It was partly due to popular pressure - people with AIDS didn't want to wait for the clinical trials. Lots of big angry protests.
And the cat and mouse game between regulators and big pharma cooking the books is also pretty mature.
There's problems with the system, but bad statistics is one of the smaller ones. The real problem is marginally effective drugs being used instead of better patent-expired ones, because the less effective (but not truly bad - they beat placebo) ones have bigger marketing budgets.
In summary, the trial looked at patients who had incurable prostate cancer that had spread and stopped responding to traditional hormonal treatments. Patients had to have no symptoms to be enrolled on this trial. The trial compared abiraterone, a new type of hormonal treatment plus steroids to just being on steroids alone. The question that the trial was asking can be framed as "Does taking abiraterone prolong the period of time that a patient can be symptom free and their cancer is under control?" That was the primary endpoint. A secondary endpoint was survival, or how long they lived.
Built in to the study design was a planned interim analysis of the data. Normally, the investigators are not allowed to just look at the data as it accrues continuously because it creates bias. It is a standard approach to allow one look at the data when say 40% of the expected events (in this case, development of progressive cancer) have occurred. When they did this, the difference between getting the drug and not getting the drug was considered big enough to unblind the trial. This means that everyone finds out if they were getting placebo or the real drug.
There are multiple reasons why one may decide to do this. First and foremost is that if the drug really works, it would be unethical to leave people on a placebo for long periods, because it is clear they have an inferior outcome. Stopping early also speeds the time to drug approval and market entry for a given indication.
There are somewhat esoteric statistical procedures that can determine at an interim analysis if the accrued data shows a statistically significant difference between groups, which would therefore justify stopping the trial, while adjusting for the impact of repeated testing on the type I error rate (ie the chance of finding an association that doesn't really exist). In this trial, there is no doubt that the primary endpoint was positive and clinically and statistically significant, even with only 40% of people on the trial having had a progression event. So they stopped. The data on whether abiraterone reduces the chance of death are not mature, because not enough of the people on the trial have died yet, so those results will be awaited. Stopping early means that these results may be biased however, because the trial is no longer blinded.
This was a large and well done trial, that employed standard statistical practices.
The placebo group... it depends on the trial. There are some trials where crossover to the active treatment is not permitted, and patients may die without getting it. The problem is that if you allow crossover, usually that means that the trial will not show a difference in overall survival, paradoxically because the treatment works really well. Regulatory bodies such as the FDA demand positive survival data in some cancers before they will approve a treatment. So it can be a difficult ethical issue, because although it sounds terrible to deprive the placebo group of treatment, if you don't prove it works then it won't get approved and nobody will get it outside of the trial.
The investigators didn't say whether they allowed crossover in this trial. It probably doesn't matter too much, because abiraterone is already approved and available at the moment for use after patients have had chemotherapy with docetaxel. So for example, patients that progressed on this trial could go on to receive docetaxel which might control their disease for a while, and then after that they could access abiraterone, so they wouldn't necessarily miss out. Is it better to have abiraterone and then docetaxel, or to have docetaxel and then abiraterone? That's an open question, which may never get tested in a clinical trial. Generally the order doesn't matter as much as being exposed to all the agents that are active. In an elderly patient who is a bit frail, I think most patients and doctors would prefer to use abiraterone up front rather than chemo, which has more side effects.
"that researchers stopped the clinical trial early to give all patients a chance to receive the life-extending medication"
And that's for one indication only. So a cancer drug might try to get approved for "4th line" use in some cancer, meaning the FDA says it's okay to use after 3 other drugs have failed. After some success there, the drug company might push to expand its label into 3rd line or front line treatment and sponsor more clinical trials to compare it to the drugs currently used at those times.
I don't know what trial this article was talking about specifically, but there were a number of other trials abiraterone did spectacularly in beforehand. Unfortunately, I don't recall the specific data from years ago when I kept up with this stuff.
Cancer drugs frequently "work", but just barely, stopping the progression of symptoms for a few months or so, and this is enough to get approved. On the other hand, you have Gleevec[1], which turned a certain variety of leukemia from invariably fatal to a death rate of just 1%. Its efficacy was noted early in the trials and got approved quickly.
Similarly, abiraterone's efficacy showed clearly in the early trials, although it's somewhere in the middle of the spectrum between "barely efficacious" and Gleevec.
Also, I would bet my last dollar the cancer will eventually find a way around it since cancer cells mutate like crazy. So it's probably a question of adding some time to the patient's life instead of curing or even controlling the disease. And there are side effects.
Don't get me wrong - if I have terminal prostate cancer I'm gonna pop these pills like candy. But it's only going to help men with aggressive prostate cancer that can't be cured with surgery because it's already metastasized.
P.S. I'm not going overboard, cancer has done a damned good job of rampaging through my family, so I think I'm excused a little drama ;)
Eh? I guess "never" is a very long time. Prostate cancer isn't communicable, and while you may pass a propensity to get cancer to your offspring that's irrelevant to the treatment.
But since my Dad died of exactly that seven years ago, and there seems to be at least some genetic component to folk who get aggressive prostrate cancer, it's cheered me up quite a bit.
Even if you have an accurate diagnosis you're more than likely to die of something else since it's mostly very slow to grow and metastasise - and the risk of having it cut out quality-of-life wise are non-trivial.
I'm in my forties. The chances that I already have prostrate cancer are about 1/3. The chances that it'll kill me are only about 3/100. The odds that a PSA test will help me figure out the difference are in coin-toss territory. The vast majority of men with prostrate cancer will die of something else (with my weight there are a lot more likely options ;-)
What I'd really love is for researchers to figure out the genetic/environmental factors that make some prostrate cancers become extremely aggressive, metastasise and kill people in months. That would be trez useful. In the mean time having a much more effective treatment for that instance is just about the second best news I can think of.
My Mom was nearly diagnosed with lung cancer but it turned out to be scarring from pneumonia. My Dad may have lung cancer and does have IPF either of which will kill him in six month to a few years.
I don't think people realize that people who are critically ill don't care if it's "Big Pharma" or some weed from China, if it works they'll try it and hope it helps even to live a few more months.
That's one of the reasons something like this is important, it's a life extending drug that's from legitimate sources, which means it's thoroughly tested and isn't some weed from China. The extra time this will give to a lot of people shouldn't be overlooked.
It's not odd at all for a trial to be ended early if the drug being tested is obviously better than the control arm. It's especially true in trials that are testing drugs for potentially lethal diseases like prostate cancer.
What likely happened was that an interim data review was conducted, the results showed that the new drug was substantially better than the control arm (and statistically significant) and the IRB and sponsoring company decided that it had an ethical obligation to end the trial and provide the drug to all the patients.
http://newsblog.mayoclinic.org/2010/03/19/study-on-stopping-... http://sciencelife.uchospitals.edu/2010/04/19/when-clinical-...
For better or worse, there's a lot of benefit from rich people dedicating their lives to beating drugs like this. In a perverse way, Mike Milliken getting prostate cancer was one of the best things for beating this cancer.
It certainly will be a lucrative, profit-making drug and the temptation will be high to milk it for all it's worth.
After all, the cancer market is so small, only one third of the entire population has cancer at any given time, it might take them more than a year to start making net profit.
Please stop defending and apologizing for billionaires.
This US is where they recover their development costs. People in poor countries just can't afford to pay what it costs to develop a drug, and the US has only so much influence when it comes to drug patents. Witness India's abrogation of patents on AIDS drugs. When you're Pfizer and Canada tells you "this is what we're willing to pay for your drug. If you don't don't like it we'll just invalidate your patent and give you nothing" you take what you can get.
>After all, the cancer market is so small, only one third of the entire population has cancer at any given time, it might take them more than a year to start making net profit.
A third of the population has cancer? Not even close. Cancer prevalence in the US is something like 12 million people,
http://www.cancer.org/Cancer/CancerBasics/cancer-prevalence
out of a population of about 314 million, which works out to something less than a 4%.
And there is no "cancer market". Cancer is a class of diseases. This drug is specifically designed to treat prostate cancer (which is itself not one disease but a class of different types of cancers that start in the prostate) that has metastasized, which isn't even most prostate cancer patients. So no, this isn't Lipitor or the next big allergy medication. They're not going to sell this to very many people, and the people who take it are very sick, so most of them won't be taking it for very long.
>Please stop defending and apologizing for billionaires.
Name one person who made a billion dollars in legal pharmaceuticals. Hell, I wish people were making billions from drugs like this one instead of adding "time release" to drugs that have been on the market forever.
1. Practically no one in the US who needs expensive chemotherapy drugs goes without them. Either the patient goes to a 340b hospital and the hospital treats for a lower or zero cost or the patient qualified for programs that the manufacturer runs where the drug is provided for free.
2. Compare the situation in the US to the UK where the gov't said "abiraterone" is not worth the price and patients couldn't get it at all, unless the paid out of the pocket for it.(1) Do you think that's a better situation than the US?
(1) The UK gov't body NICE just decided in May to approve the use of abiraterone because the company decided to offer a discount. The current cost is a little under 3000GBP/month.
Reading http://www.nice.org.uk/newsroom/features/measuringeffectiven..., that is exactly what they try to do.