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A passion for solving research puzzles

Biostatistician Amalia Meir guides the design and data interpretation of HIV and herpes clinical trials

Nov. 17, 2005
Amalia Meir

PHS biostatistician Amalia Meir co-authored a paper on statistical-methods research that will be used as a guide for designing future SCHARP studies.

Photo by Todd McNaught

Dr. Amalia Meier was teaching junior high and high school science as a Peace Corps volunteer in western Africa in the early 1990s when she first starting seeing the impact of AIDS. Funerals were common following a "fever" or "lung infection," but the true cause — a growing number of AIDS cases — wasn't discussed or even well recognized.

"I thought, 'Wow, there are really a lot of health issues that are so basic.' I was watching these young kids, and I knew they had a poor chance of becoming adults and having healthy families." In that realization, she discovered the field of public health, which ignited her passion for research.

Her goal? "I wanted to make an impact for women who don't have as many choices as I do. I would love to be anywhere near the team that creates an HIV vaccine," she said.

With graduate school on the horizon, Meier left the African country of Gabon for her Michigan home, got a Master's degree in Applied Statistics and came to the University of Washington in 1997 to pursue her doctorate in Biostatistics.

Meier began work at the Hutchinson Center in 2002 as a postdoctoral fellow with Dr. Ben Masse in the Public Health Sciences Division's Statistical Center for HIV/AIDS Research and Prevention (SCHARP). A faculty member for the UW's Laboratory Medicine program since 2004, she now also holds a joint appointment with the PHS division's Program in Biostatistics.

"They were doing the types of clinical trials I wanted to be involved in," said Meier of her enthusiastic desire to work for SCHARP.

Statistical-methods research

Meier's joint appointment formalizes her numerous collaborations with Center researchers and allows her time to do statistical-methods research. She and SCHARP's Dr. Peter Gilbert recently published a study-design paper gauging accuracy of conclusions about an intervention when specific differences appear between subjects in different treatment arms of a clinical trial. For example, study participants in different parts of a study may attend clinic visits more or less regularly, and such differences may cause bias or reduce the study's statistical power. Their findings appeared in the October issue of the journal Contemporary Clinical Trials. SCHARP's researchers will use the results as a guide in designing future studies.

Meier spends the bulk of her time working with UW researchers and graduate students on trial design, sample size calculations, statistical analysis and scientific reports for the UW's Virology Research Clinic. The clinic studies the family of herpes viruses, which cause conditions ranging from cold sores and mononucleosis to chicken pox and roseola.

Studies have shown that genital herpes is a risk factor for the transmission and acquisition of HIV. At least half of the HIV-infected people worldwide are infected with herpes simplex virus type 2 (HSV-2), the primary cause of genital herpes. These coinfected individuals may be significantly more likely to transmit HIV than others because they appear to shed larger amounts of HIV in their genital secretions. Conversely, people who do not have HIV but do have genital herpes are about twice as likely to become infected with HIV if exposed than people who do not have genital herpes.

Meier provides statistical support for a large-scale international herpes study through the UW School of Medicine. At multiple sites in Africa, the Gates Foundation-funded study of more than 3,000 mixed HIV-status couples is the first ever to evaluate whether it is possible to reduce transmission of HIV by treating genital herpes with acyclovir, a generic herpes medication. The researchers believe the treatment could reduce HIV transmission by 50 percent. If successful, the year-old study could lead to an important new approach to HIV prevention in developing countries.

"It's a huge study, and it's exciting," Meier said. "The possibility of being able to treat herpes and have an impact on HIV acquisition is compelling. It goes back to women-empowerment issues. The women I knew when I was in the Peace Corps had a lot of pressure on them to be a certain way. There's no good answer for them. Even if they can negotiate birth control, then they can't have children."

Dr. Anna Wald, one of the study's co-investigators and head of the Virology Research Clinic, appreciates her collaboration with Meier. "She listens well, and she explains biostatistical concepts in a way that is easy for physicians to grasp," Wald said. "Amalia is willing to try new things, which is, after all, what research is about."

HHV-8

Meier is also studying human herpes virus 8 (HHV-8), which is spread through saliva and sexual contact. In collaboration with Dr. Corey Casper at the UW, she is working to determine if HHV-8 is a risk factor for acquisition of HIV, how prevalent it is in at-risk teenagers and if there are correlating sexual behavior risk factors. HHV-8 is important since it is a necessary prerequisite to acquiring Kaposi's sarcoma, a cancer of the tissues under the skin or mucous membranes that line the mouth, nose and anus. Kaposi's sarcoma is often seen in immuno-compromised AIDS patients.

Some types of herpes infections are found in all people and are relatively benign. For example, human herpes virus 6 (HHV-6) is routinely acquired by age 2 and causes a brief acute infection with fever and diarrhea. Working with the UW's Dr. Danielle Zerr, Meier helped determine whether the febrile seizures sometimes experienced by babies with high fevers were related to HHV-6. While the researchers didn't find a connection, they are working to help physicians distinguish viral from bacterial infections to prevent the over-prescribing of antibiotics.

Researchers know that the power of a study is due in large part to the strength of its design and statistical methods. Meier collaborated with Drs. Jim Hughes and Barbra Richardson, both PHS scientists and Meier's former thesis advisers, on a project about how to estimate virus acquisition even when the diagnostic tests are not completely accurate. For example, the antibody test for HIV is wrong one way or the other some of the time. The researchers showed that even without being able to confirm individual results, an overall inaccuracy rate for the test could still be estimated, leading to a correct estimation of acquisition rate and risk factors for acquisition.

'Motivated by challenges'

"Amalia has great insight on the link between medicine and statistics," said Richardson. "Her ability to understand scientific problems and apply statistical methods — and develop new ones — and explain the analyses to investigators in a clear manner makes her a great statistician. Plus, I enjoy her great attitude and fun nature."

In her off-hours, Meier indulges a zeal for quilting on a near-daily basis. She approaches her hobby with the same intensity and curiosity with which she tackles her career. "Quilting is an outlet for expression and a way to produce something that's very satisfying," she said. "For me, the more you know, the more you want to know. There's so much to learn and see and try. I've gotten feverish about artistic expression." Meier creates two to three large quilts each year based on her original designs and sometimes shows them at the Pacific Northwest Quiltfest.

Meier chuckles as she explains a common reaction to her virology research. "People say to me, 'Gross! Why do you want to study herpes?' But I'm motivated by challenges. I like the puzzle-solving aspect of research," she said. "There's always another study coming up, right on the cutting edge, whether in herpes or HIV research, and I get to be involved in it coming to fruition. It's such a great stage because everything's possible right now."


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