Prostate cancer drug so effective trial stopped

http://www.sfgate.com/cgi-bin/article.cgi?f=/c/a/2012/06/02/MNI11ORI84.DTL

by joeyespo • 14 years ago

149 51 14 years ago

pixelcort• 14 years ago

This has interesting implications to the recent discussions about A/B testing and Multi-armed bandit algorithms.

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?

planetguy• 14 years ago

at what point was the trial stopped? Was it stopped before there was statistical significance?

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.

DanBC22• 14 years ago

> 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.

jerf• 14 years ago

We are hearing about this precisely because it is unusual and thus newsworthy. This article is light on the scientific details. Given those things, let's extend them the benefit of the doubt for now and hold the standard (and somewhat tedious) litany of complaints until there's more evidence that they are called for, as exceptional actions in such a tightly regulated domain is reasonably likely to imply exceptional circumstances.

Mvandenbergh• 14 years ago

No. The effect size was large enough that the statistical significance agreed with the FDA before the start of the study was reached well before the end of the trial. This is not uncommon, and the possibility of ending the trial early will have been decided beforehand. Usually an independent advisory board not affiliated with the FDA or the pharma company will make these decisions - the other parties may not even have known that the results were better than expected until the independent board decided to end the study.

Gatsky2• 14 years ago

I was at the announcement of the trial data by the investigators this morning. The results were also discussed by a statistician not involved with the trial directly. Not sure that hacker news needs an in depth analysis of the trial design and outcome, but anyway...

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.

firebones• 14 years ago

Does the placebo group get the option of getting the med at the time of termination, or do they have to wait for approval along with everyone else? What about the group already getting the med? Do they stay in?

m104• 14 years ago

No interesting implications, just the reaffirmation that real significance is more important than statistical significance.

novalis• 14 years ago

This brings great hope to all affected and I hope it gets approved and helps the people that have not gone through chemo yet, as stated in the article.

geuis• 14 years ago

Story is a bit light on details. Can anyone provide links to the study and the rationale behind ending it early?

notatoad• 14 years ago

according to the commenters on reddit, the rationale behind ending it early is that this is how clinical trials work. A trial is run until it is statistically clear that a drug is either better or worse than the current market leader it is being compared against. The trial might be ending earlier than expected, but it is not being cut short. The success metrics were reached.

refurb4• 14 years ago

Clinical trials are monitors by IRBs (institutional review boards) that independently monitor the trial to ensure that it is being conducted ethically.

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.

khuey• 14 years ago

It's more complicated than that.

http://newsblog.mayoclinic.org/2010/03/19/study-on-stopping-... http://sciencelife.uchospitals.edu/2010/04/19/when-clinical-...

ceejayoz• 14 years ago

Essentially, it appears to work so well the review board feels it's unethical to withhold the treatment from the control group.

RexRollman• 14 years ago

Let's hope that this drug works as well for everyone as described in the article.

tshtf• 14 years ago

Apparently this drug[1] was discovered at non-profit Cancer Research UK[2], not a drug company.

1. https://en.wikipedia.org/wiki/Abiraterone

2. https://en.wikipedia.org/wiki/Cancer_Research_UK

mrkmcknz• 14 years ago

Johnson & Johnson own the rights to this drug they purchased it sometime ago I believe.

ars2• 14 years ago

Yah, it was discovered in 1990, and goes off patent in 2 years.

pbhjpbhj• 14 years ago

The Wikipedia article for https://en.wikipedia.org/wiki/Abiraterone says that they acquired the license to produce the drug based on acquisition of a licensee. If true then they have licensed a right rather than owning "the rights".

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?

refurb4• 14 years ago

And I'll bet that some of the research that resulted in the drug being discovered by Cancer Research was not conducted by Cancer Research UK. And I'll bet that Cancer Research UK never could have taken the drug to market because they didn't have the expertise to do so.

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.

fl3tch• 14 years ago

Pretty much. The idea that a lone polymath experimenting in his basement, a la Ben Franklin or James Maxwell, could make a genuinely important scientific discovery, disappeared a long time ago. We're chasing the long tail of knowledge. Each increment will get harder, more complex and more expensive over time, and that's factoring in the technology that makes modern science so much easier and cheaper, or even possible.

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.

domwood3• 14 years ago

As someone who's grandfather and grandmother both died of cancer-related complications (edit: in the last four months, my grandmother not even a week ago) and with a grandfather-in-law who has terminal cancer, for once I'm going to abandon cynicism, gloss over the lack of scientific details, and dare to hope.

tsotha6• 14 years ago

Don't go overboard. This drug works by suppressing the ability of cancer cells to produce testosterone, which prostate cancer cells need to grow. So it isn't effective against any other type of cancer.

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.

domwood3• 14 years ago

No, it's no wonder drug, it's not a cure, it's a treatment. Yes, it probably will become redundant eventually, but as cancer's a genetic thing, it'll be on a patient by patient basis, that means even if a patient's cancer start to develop an immunity to the drug, it'll take a very long time for that immunity to be spread by reproduction, especially as people tend to get cancer after having children (it's far more common in later life after all, or don't have them after they are diagnosed. That means that it'll be useful for a long period of time for the majority of people. In the meantime, that gives science a chance to continue to develop the "next step", whatever that may be. And it's not the only drug of its kind, we've got to the point of being able to target individual cancers, so perhaps the research from this will have uses elsewhere.

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 ;)

adrianhoward2• 14 years ago

But it's only going to help men with aggressive prostate cancer that can't be cured with surgery because it's already metastasized.

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.

dhughes• 14 years ago

Sorry to hear about your family's health, it certainly is humbling as a human to hear that news.

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.

domwood3• 14 years ago

Thanks, and the same to you, IPF isn't fun and neither is lung cancer.

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.

ck22• 14 years ago

Now let's hope people in the USA without insurance can afford it.

It certainly will be a lucrative, profit-making drug and the temptation will be high to milk it for all it's worth.

tsotha6• 14 years ago

If by that you mean the drug company needs to recover development costs plus enough to cover drugs that never made it to market, then... yeah.

ck22• 14 years ago

Right, just like they charge a fraction of the price outside the USA vs pumping insurance for all it's worth in the USA.

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.

ars2• 14 years ago

It's an old drug - it goes off patent in two years.

refurb4• 14 years ago

Two comments:

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.

arethuza• 14 years ago

It's not a choice in the UK between the NHS or pay or it yourself - you can have private health insurance if you want.

Someone• 14 years ago

I know it sounds harsh, but at that price point, I can understand that. Money is finite, and choices must be made. That £3000 a month could possibly be spent elsewhere with greater benefits for the health of the society.

Reading http://www.nice.org.uk/newsroom/features/measuringeffectiven..., that is exactly what they try to do.

losvedir2• 14 years ago

Ah, yes, abiraterone. In another life, when I did equity research, we covered Cougar Biotech (the owners of the drug before JNJ). Even then (years ago), it was clear this would be a successful drug. Glad to hear science and drug development are moving forward!

lonnyk• 14 years ago

Please elaborate on what made it clear so long ago.

losvedir2• 14 years ago

It did very well in all its trials. To get approved for use in any indication a drug has to go through a number of clinical trials - a Phase 2 in a small group of patients and multiple Phase 3's in a larger group.

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.

[1] https://en.wikipedia.org/wiki/Imatinib

mathattack• 14 years ago

Great news!

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.

Prostate cancer drug so effective trial stopped

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