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NIH orders scientists to test new drugs on animals of both sexes

May 20, 2014 at 6:30 PM EDT
The National Institutes of Health announced that it will require scientists to test new drugs on both male and female animals. Until now, most early trials have been conducted on males. Judy Woodruff joins Dr. Janine Clayton of National Institutes of Health and Phyllis Greenberger of Society for Women's Health Research to discuss the past problems driving the decision.
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JUDY WOODRUFF: When you see headlines about a new drug on the market, chances are you have rarely thought about the gender of the lab animal the drug was first tested on during trials, but, in fact, most early trials are conducted on male rats or other male animals.

Researchers say that gender difference has led to a significant impact after a drug comes to market. Last week, the National Institutes of Health announced that it is requiring scientists to test their work on both male and female animals.

For some insight into what’s behind these changes and what it means, we turn to Dr. Janine Clayton. She’s the director of the National Institutes of Health’s Office of Research on Women’s Health. That’s the agency that announced the change. And Phyllis Greenberger, she’s the president of the Society for Women’s Health Research. She has long advocated for this change.

And we welcome you both to the program.

Dr. Clayton, let me start with you.

Why does the sex, the gender of the animal or the cell where the test is being conducted make a difference?

DR. JANINE CLAYTON, National Institutes of Health: The sex of the cell makes a huge difference, because the pre-clinical studies, where we’re testing drugs or therapies, are those studies that build the evidence base and inform the clinical studies.

So if you are going to be studying a disease that affects both men and women, it’s really important to think about male and female cells and males and females in the animal model work when you are doing that pre-clinical research.

JUDY WOODRUFF: Phyllis Greenberger, as we said a minute again, this is something that you and your organization has been focused on for a long time. So, this is something that has been known for a long time.

PHYLLIS GREENBERGER, Society for Women’s Health Research: Well, it’s been known, let’s say, within a certain portion of the research community.

I don’t know that it’s still generally accepted by everyone and I think it’s still going to take a while before it filters out among all research scientists. But there was a lot of pushback for a long time and so, obviously, we’re thrilled finally that this is getting the attention.

JUDY WOODRUFF: And is that the reason that it wasn’t done earlier, Dr. Clayton, that there was just pushback in the scientific community?

DR. JANINE CLAYTON: It’s hard to say. There are probably a lot of factors that are involved.

And what’s really important now is right now we have been able to put the focus on getting this as a priority. As Phyllis mentioned, the Society and other advocacy groups and scientists and others have talked about this in the past. In fact, we are supporting scientists who are doing this research, but it wasn’t enough of a priority. In some way, it was like a blind spot. Scientists weren’t thinking about it.

JUDY WOODRUFF: Phyllis Greenberger, were there — were there actually individuals who were harmed or where help wasn’t delivered because the research was done only on males?

PHYLLIS GREENBERGER: Well, when you talk about males, you’re talking about not only male animals or male cells, but we’re talking about in terms of clinical trials and the inclusion.

So when we started looking at the whole issue of the lack of inclusion of women in clinical trials was 25 years ago, when mostly males were in clinical trials. And we worked with Congress to get women, and get women and minorities in clinical trials. That was really defined as phase three.

Nobody — and we were told that the NIH felt that that was basically what they could do. No one talked about animal models or cells or even phase one and two, which is still where we need to go to some extent.

JUDY WOODRUFF: OK, without getting into phase one, two, and three.

PHYLLIS GREENBERGER: Right, without getting into all the details.

But, actually, I think the — what really started it is that there was an Institute of Medicine report that the Society commissioned and finally came out in 2001 that said that every cell has a sex, and that was sort of the beginning I think of really recognizing how far back this research had to go to understand sex and gender differences.

JUDY WOODRUFF: And, Dr. Clayton, what’s involved now for scientists now that they’re told they have to think about this? What’s involved in doing that?

DR. JANINE CLAYTON: So we’re calling on scientists to take sex into account when they think about their pre-clinical experimental design.

So they are going to need to take a balanced approach in looking for male and female differences in cells in animal work. The reason why that’s so important is because that’s what drives the benefits, the clinical benefits, so that men and women can benefit from medical research.

JUDY WOODRUFF: But how hard is that?  Does that mean — is it extra work, is it more expensive? What’s involved in making sure there’s a gender balance?

PHYLLIS GREENBERGER: Both.

DR. JANINE CLAYTON: The first thing, from my perspective, is recognizing and understanding this and thinking about it differently and taking it into account in the design and the perspective of the experiments that they work on.

So we’re going to be talking about that in terms of releasing our policies and also training materials, where we will go through the multiple strategies that people can use. There’s no really one way, because it depends on the scientific context and the research being performed.

JUDY WOODRUFF: And I want to ask you the question that I was asking Phyllis Greenberger a moment ago. And that is, are there instances you can cite where harm was done or where help wasn’t provided because research was done only on males?

DR. JANINE CLAYTON: Well, clearly, we’re all concerned about harm, and not considering sex and gender and how that might affect that is something of concern.

I guess the real answer is, we will never know the number of women that weren’t treated appropriately or the number of men that were missed in terms of diagnosis. For example, a woman may not have chest pain, crushing chest pain, when she’s actually having a heart attack.

She just may have some pain in her jaw, feel really sleepy, and not be doing well, overall extra fatigue. And if she comes to an E.R. doc and says that, she may not get picked up as having an actual heart attack.

JUDY WOODRUFF: And that’s…

PHYLLIS GREENBERGER: But there are — actually, there are instances — we have commissioned — or worked with Congress for a Government Accounting, a GAO report, a number of years ago — this was in I think 2000 — and it turned out that eight of the 10 drugs that had been taken off the market had disproportionately adverse effects on women.

And one was a cardiovascular drug that actually caused heart failure in women. So, it’s hard to know at this point whether — whether risk factors or side effects for women are because the drug wasn’t tested, that it’s just an individual.

And, you know, everybody is different anyway, and so you may have a risk factor that I don’t, even though we’re both female. But it’s difficult to know about — all about the risk factors across the board, what it had to do with, but we know from the GAO report that that was an example.

JUDY WOODRUFF: But, in any event, now you’re saying it will make a difference because — because now female and male subjects will have to be part of the testing.

DR. JANINE CLAYTON: Absolutely. And the female animal models and the female cells will have to be used in the studies where we’re testing drugs to see if they might be effective.

JUDY WOODRUFF: And scientists will go along with this?

PHYLLIS GREENBERGER: Well, as I said, it’s taken 25 years to get to this point. I don’t think it’s a slam dunk. I think it’s going to take a while.

You asked the question, what was the resistance? I think part of it was just understanding that this is important and that there are differences. But we’re — female animals turned out to be more expensive than male. Male rats and mammals are less expensive than female, and it’s more complicated and probably more expensive to be able to do research on both, as opposed to one. So I think there’s going to be — you know, there are some complications and it will take a while for the change to occur.

JUDY WOODRUFF: Well, it’s something that I know that we — it’s important to take note of, and we appreciate you both being here to help explain it to us.

PHYLLIS GREENBERGER: Yes. Well, we — I appreciate the opportunity.

(LAUGHTER)

DR. JANINE CLAYTON: I’m delighted to be here.

JUDY WOODRUFF: Dr. Janine Clayton, Phyllis Greenberger, we thank you both.

DR. JANINE CLAYTON: Thank you.

PHYLLIS GREENBERGER: Thank you.