men are eligible for only 1 in 3 breast cancer clinical trials

In a recent post I discussed the underfunding of basic research on the male form of breast cancer, and advocated for 1% of breast cancer research funding to involve male disease, in proportion to 1% of breast cancer patients being men. So what about clinical trials?

When it comes to eligibility for trials it is easy to get a feel for the situation on ClinicalTrials.gov, a great resource for finding clinical trials.

Using just the basic search you can learn that there are 38,466 ‘cancer’ studies available, and that of these 5,287, or about 14% include breast cancer (search done on 5/10/13). The question of whether men are included can be asked in two ways: which trials (also) focus on male breast cancer, and which trials allow men to enroll.

For the former, you can see that when you add ‘male’ to the search the number drops from to 489 out of the 5,287, or less than 10% of the breast cancer trials. Pretty good when you consider that only 1% of the patients are male, but not as inclusive as it could be.

When you ask for trials in which men can enroll it looks much better. About 1/3 of trials allow men to enter – higher than 10%, and high when you consider only 1% of the patients are men. But that is not the way to think about it. Its really about equal access, and from that point of view 1/3 is pretty dismal.

I took an in-depth look at this question, and downloaded all ‘breast cancer’ trials from clinicaltrials.gov on 5/5/13 (there were 4,826), and prepared some visualizations.

Here is the spreadsheet (link added to post 6/21/13):

clinicaltrialsdotgovbreastcancer

Please note that this data set includes trials in all stages of activity (i.e. including ones that are closed, withdrawn, not open yet etc.) and types (interventions, observations) and also that not all the trials are focused on breast cancer, but may include breast among other diseases, for example if they are for all advanced cancers, or all metastatic cancers etc.

Please also note that the data are a mess – for example the field ‘condition’, where the trial declares what kinds of disease are included, can include several dozen synonyms for breast cancer (see figure). I grouped these, but imposing order on this is not easy – so this is a caveat. Another aspect of these data is that a trial can appear several times in some of the graphs that follow. For example, it may be sponsored by several entities, include more than one intervention, have multiple age groups, funders and be for different conditions too etc.

breast cancer as a condition in clinicaltrials.gov database appears in many different forms

breast cancer as a condition in clinicaltrials.gov database appears in many different forms

While there are almost no trials for just men, around 1/3 of trials allow accrual of both genders (see pie chart top left of this visualization).

gender

When you slice the trials into different groups by type of intervention, age group, funding source, phase of the trial, study design, study type, recruitment state and condition  the 1/3 ratio holds pretty well. There are some outliers, such as Phase I trials which appear to allow accrual of men to nearly 60% of the trials in this group. NCI sponsored trials also beat the ratio, with 40% of their breast cancer trials including men as eligible.

So then I asked the related question: taking all the breast cancer trials for which men are eligible, what kinds of trials are these?

In this visualization I have put the numbers of trials on the graphs, so that you can quickly get a feel for what is being done. The distribution looks pretty much the same as for all the breast cancer trials, but you can now see for example that there are 973 drug trials, or 612 phase 2 trials in the data set. You can see that the majority of trials are interventional (1,301) not observational (252).

male eligible

Of course the trials of highest interest are the ones that you can join as a guy, and many of the trials in the data are already closed or not yet open. So in the next vis I am showing the trials for which men are eligible that are are recruiting in some manner. You can see that there are currently just under 500 drug trials recruiting men, and you can see the individual trials below the graph. There is a URL to the trial webpage in the tool tip, which you get when you hover over the colored square at the right of each row in the table (only works in the live vis – please use link above). On those pages you can see further details of what the trial is all about.

available

Interestingly, in this group there are only two trials that are “men only”:
1) the observational study by the EORTC which also includes US centers (MD Anderson Cancer Center and Fred Hutchinson Seattle Cancer Care Alliance), which aims to gather retrospective data on a large cohort of men to see how they fared clinically.
2) A Prospective, Randomised, Multi-centre Phase II Study Evaluating the Adjuvant, Neoadjuvant or Palliative Treatmant With Tamoxifen +/- GnRH Analogue Versus Aromatase Inhibitor + GnRH Analogue in Male Breast Cancer Patients (MALE)  by the German Breast Group. This trial tests whether aromatase inhibitors can be made useful in men by adding in gonadotropin-releasing hormone analogue which could disrupt the other source of estrogen in men that is independent of

Of course trials are opening and closing all the time so to do a search right now on interventional breast cancer clinical trials that are in the ‘recruiting’ state click here and book mark the page! Numbers will vary as the database is refreshed regularly.

Of course to get into a trial you’ll have to find out if it is being offered near where you are (or are willing to be), and consider the other inclusion criteria related to disease state, treatment stage, etc etc. You can refine the search using the “modify this search’ link at the top, and add in these other factors to see a list more likely to meet your needs.

Lastly, let’s look at what kinds of numbers of men are actually being accrued? I searched for interventional breast cancer trials that were complete and had reported results. I found 42 trials that were truly focused on breast cancer, and found that accrual of men across this group was about 0.8%, or close to the relative incidence of the male disease.

Here is the spreadsheet (link added to post 6/21/13):

completed interventional with results and men

actual accrual

So in summary, access to trials is not as good as it needs to be from an equity point of view. Having access to only 1/3rd of the clinical trials in a disease group is not adequate and excludes men from many opportunities to benefit from recent advances, and make contributions to understanding their disease and the disease in general. I understand that some trials may well focus on aspects of breast cancer that are not relevant to men – fair enough, and this is analogous to the MALE study described above. There could be more for men like this.

So I propose that  any breast cancer clinical trial which men does not  include men be asked to provide a strong biological rationale for this omission. 

Amongst the trials that do allow men to enroll, it appears from an admittedly small sample that, broadly speaking, men are being accrued at a rate that reflects their prevalence. Some programs do better than others, naturally – there are some trials that have large accruals and no guys.

I know that at MD Anderson we study and report the proportion of patients with different ethnicities that we accrue to trials, in the context of our overall patient mix. By analogy I think that large clinical trials centers should keep an eye on whether they are actually accruing men to breast cancer clinical trials – its not just about the right to be accrued, but about actually being accrued.

Of course, when you consider that 2/3rds of trials don’t even consider men, then you can see that there is likely a lot of ground that needs to be made up.

3 thoughts on “men are eligible for only 1 in 3 breast cancer clinical trials

  1. Oliver, first your use of pink and blue is very compelling. The blue is a tiny sliver in a sea of pink.

    Secondly, I used to work in the health disparities area in terms of access to mental health services being disproportionate across race and income. I know that there are income and racial disparities in breast cancer assessment and treatment. I am guessing that there is a branch or sub-branch of the National Cancer Institute that is devoted to health disparities. Although males are not usually considered the focus of disparities research, I am wondering if you have gotten any read from the funding agencies about whether this might be a fruitful avenue by which male cancer research could be increased.

    in the research I did within NIH (NIMH and NIDA), there were increasing requirements over the years to recruit a representative sample of research participants in terms of race, ethnicity, and social-economic status. There was also a call for more fathers (I did research on kids) in research studies but fathers still do not volunteer to be in research studies very often, in my field, which focuses on families. And then the research gets built up on models of mothers and their children and investigators don’t even try all that hard to recruit men because the assumption is that the sample size is going to be too small. (Sample size is a major problem in my field due to a number of factors.)

    One of the nice things about health disparities research is that there has been a focus on strategies for improving recruitment techniques for underrepresented groups who not only less likely to be included in research studies but also less likely to join a study even if invited.

    Anyway, you may be well aware of this field, but I thought I’d mention it in case it is useful to your campaign.

  2. Elizabeth – thank you for this insight. I had not considered this angle. As a white male I rarely think of myself as someone receiving disparate treatment… But the tools of that discipline are of course the right way to ask these kinds of questions. I will discuss with some of our health disparities experts here at work.

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