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Issue #144: September 28, 1997
FASTFAX is available by fax in the 215 and 610 area codes at no cost, or by mail anywhere for $20.00 per year, by calling 215-545-6868, and by E-mail by contacting and type the message SUBSCRIBE in the message section. Sources for some information in this issue include Philadelphia Inquirer, Reuters, Washington Post.
FDA may mandate inclusion of women in trials
Lower survival seen in older HIV+ patients
ACT UP protest demands needle exchange funds
FDA group urges approval of Paxene for KS
SUPPORT WE THE PEOPLE THROUGH THE 1997 AIDS WALK!
FDA may mandate inclusion of women in trials
After waiting several years for companies to voluntarily include women in clinical trials of AIDS-related and other serious and life-threatening diseases, the U.S. Food and Drug Administration (FDA) is proposing to make inclusion mandatory.In 1993, the FDA reversed course and determined that it was now acceptable to include women of child-bearing potential in clinical trials, but only for serious and life-threatening diseases. "Although we have a policy of inclusion and we have tried to jawbone companies to include women..." in this area, "...fully one-quarter of trials continue to automatically and systematically exclude women," FDA Deputy Commissioner Mary Pendergast said. "The voluntary system wasn't working successfully enough."
The proposal is also partly in response to recommendations that women with HIV or AIDS not be excluded from trials just because they are of child-bearing age. The suggestion was made by the National Task Force on AIDS Drug Development and the Presidential Advisory Council on HIV/AIDS.
Companies generally get approval from the FDA in regard to trial design before proceeding with studies. The agency has the power to delay a trial if there is concern about improprieties. Under the new proposal, the agency would expand its ability to put a trial on hold if the company proposes to exclude or improperly excludes women.
Pendergast says she "assumes" that companies have been hesitant due to liability concerns, but says those worries can be addressed through informed consent. Going into trials, "...women will be advised about what is known and what is not known about [a] drug." And, she says that the FDA anticipates that women will be given pregnancy tests before entering trials, and advised to use contraceptives while under study. The agency does not expect firms to enroll women who are already pregnant.
Pendergast also points out that women who will be entering the studies are not healthy volunteers, but those who are already sick. The FDA is not setting a recruitment quota for trials, but Pendergast notes that, by approval time, firms will have to include enough aggregate data on women to satisfy the agency and its outside advisers.
The proposal will not apply to trials designed to test drugs for gender-specific diseases, or men-only trials, as long as women-only trials are also conducted.
The agency published the proposal in the Sept. 24 Federal Register. Written comment will be accepted over the next 90 days, and then a final proposal will be issued.
Lower survival seen in older HIV+ patients
There is a survival gap between older and younger patients infected with HIV that appears to be widening, according to the National Institutes of Health.At a conference on HIV/AIDS and aging sponsored by the NIH, researchers pointed out that little is known about either the course of the disease or the psychosocial adjustment of people in their 50s and 60s with HIV infection.
While survival of HIV-infected patients overall has been steadily improving, Dr. Sharon Weissman, director of the infectious disease clinic at the Cleveland, Ohio Veterans Affairs Medical Center, said survival in older persons is very low. Data from several sources, including the medical center and the Centers for Disease Control and Prevention, show that ten-year survival rates after seroconversion range from 86% in the youngest age group, those younger than 15, to just 12% for those older than 55.
This gap is not explained by risk behavior, income, gender, or CD4 cell count. It may be due in part to comorbid disease, access to care, treatment response, and compliance with often complex therapy. "We know that when side effects increase, adherence decreases," she said.
Dr. Stephen Crystal, director of the AIDS research group at the Institute for Health, Health Care Policy, and Aging Research at Rutgers University, presented preliminary data indicating that the care of older patients with HIV and AIDS may differ from that for younger patients. In a cohort of New Jersey Medicaid recipients with HIV and AIDS, patients over the age of 50 accounted for greater use of residential long-term care and longer hospital stays compared with younger patients, but slightly lower use of inpatient services and apparently less utilization of intensive care.
"There may be a pattern of less frequent but longer hospitalizations, which may more often involve supportive, palliative, or terminal care...We're going to have start getting inside the black box of hospitalizations to see what's going on," Dr. Crystal said.
People 50 years of age and older have consistently made up approximately 10% of the reported AIDS caseload since the start of the HIV epidemic, and their numbers are greater than those of the pediatric population, which typically gets more attention, speakers noted.
Sexual transmission continues to be the predominant cause of infection for older patients, with rates decreasing for homosexual transmission and increasing for heterosexual transmission with age, according to Dr. Marcia Ory, chief of social science research on aging at the NIH's National Institute on Aging.
Dr. Ory pointed out that older people are less knowledgeable than younger groups about HIV risk factors and more likely to believe that the virus can be transmitted by casual contact. While older adults are less likely to engage in risky behavior compared with younger adults, those who do are less apt to take precautions against infection or to be tested for HIV, Dr. Ory said.
Recognition that a significant portion of AIDS cases are in middle-aged and elderly patients is crucial to prevention efforts, according to Dr Ory.
"We can't ignore the older population, and have to understand the role they're playing in the HIV/AIDS epidemic," she said.
Ory said she believes stereotypes surrounding older individuals have kept their health providers from realizing the threat of HIV infection in their more senior patients. People "don't think that older people have sex, or they don't think older people use drugs," Ory explained.
And since both patient and doctor may dismiss the idea of AIDS as a possible diagnosis, geriatric AIDS cases are apt to be spotted only in late-stage disease. Ory says older HIV-infected individuals often "present with things that could be AIDS-related symptoms, like fatigue and pain." But because AIDS is not often on their diagnostic 'radar', physicians may blame these patient complaints on "aging-related disease, not AIDS."
New treatment developments, such as protease inhibitors and drug combinations, may also contribute to the "graying" of the AIDS epidemic, Ory contends. "With these new drugs, there's the possibility that people will be living longer with HIV," she explained.
Ory believes the majority of older individuals have lifestyles which put them "at less risk" for HIV infection than the young. However, Ory points out that of those who do engage in risky behaviors, "Less than 20%... are using condoms." Older individuals are also much less likely to go for regular HIV testing than younger people, she said.
ACT UP protest demands needle exchange funds
Hundreds of AIDS activists descended on the Department of Health and Human Services last week in protest of the ban on federal funding for needle-exchange programs/Some protesters, mostly from Philadelphia, were arrested after trying to carry a 12-foot 'moral backbone' into the building for HHS Secretary Donna E. Shalala, who has said needle-exchange programs can be effective in fighting AIDS but has stopped short of lifting the ban.
President Clinton was also a target of the protest, which was sponsored by the National Coalition to Save Lives.
Federally funded needle-exchange programs are at the heart of a brewing national controversy surrounding the prevention of AIDS. There are currently 87 needle-exchange programs operating in the country, all with local or private financial support. In order to lift the ban on federal funding of the programs, Shalala must certify that the programs reduce AIDS without increasing drug use.
Shalala reported to Congress in February that there is research showing "drug use did not increase when communities began needle exchanges, and that the programs allowed health officials to offer drug treatment to addicts they might otherwise never see." However, according to HHS spokesperson Victor Zonana, the department "is still studying whether needle-exchanges increase drug use." Zonana said, "We will make a decision based on science and public health, not politics."
Mark Kinzly, who runs a needle-exchange program in Bridgeport, Connecticut, said, "They put this whole thing on a political and moral issue rather than a health issue. The small amount of money we would spend on needle exchange would save us millions of dollars every year."
Meanwhile, Congress continues to struggle over the issue as a result of a House budget amendment which would formally prohibit federal funding for syringe exchange programs. Because no similar amendment was passed in the Senate, the success of the House action depends on the outcome of a "conference" between the two legislative bodies that will iron out differences in the two budget bills.
"If the house language survives the conference, federal funding for needle exchange is dead," said Paul Davis, a spokesperson for ACT UP/Philadelphia.
"The white house has failed so far to apply any pressure on the conferees," Davis said. "Had Bill Clinton used his clout, the House amendment might not have passed in the first place."
Davids noted that liberal Philadelphia Democrat Chaka Fattah, along with 59 other Democrats, joined the effort to permanently prohibit federal needle exchange funding.
ACT UP is calling on advocates to contact President Clinton and ask him to pressure HHS Appropriations Conference Committee members to preserve Secretary Shalala's authority to lift the federal funding ban on syringe exchange. The phone number to the White House is 202-456-1111. ACT UP is also recommending phone calls to Pennsylvania Sen. Arlen Specter, who co-chairs the Senate committee, at 800-972-3524.
FDA group urges approval of Paxene for KS
The U.S. Food and Drug Administration's (FDA) Oncologic Drugs Advisory Committee has voted unanimously to approve a new formulation of paclitaxel to treat patients with advanced AIDS-related Kaposi's sarcoma (KS) who have failed to respond to first- or second-line chemotherapy, including liposomal forms of daunorubicin and doxorubicin (Doxil).Paxene's manufacturer, IVAX, is seeking FDA approval even though Bristol-Myers Squibb's Taxol is already approved and has orphan status for the same use. With orphan status, Taxol gets 7 years' marketing exclusivity to KS patients.
For IVAX to get approval, Paxene would have to be determined to have some superiority to Taxol, or be chemically different, said NaPro CFO Gordon Link. IVAX claims that Paxene is a different formulation than Taxol. The committee was not charged with making that decision, but did question how it might be different. Panelist Dr. David Johnson of the Vanderbilt University Medical School said, "That's still to be determined."
Dr. Gregory Harrison of Baker-Norton told the panel that Paxene is as effective and as safe, and in some incidences, safer than Taxol, but did not offer large amounts of data to support the claim.
In an 89-patient, Phase II study, 46% of patients overall had a complete or partial response, although there were only two complete responders, said the firm. Among those who had not responded to two previous courses of chemotherapy, there was a 41% response. For those who failed previous Doxil therapy, 33% responded to Paxene. FDA reviewer Ken Kobayashi said that the FDA analysis found overall response to be 42%, with no complete responders.
The drug was given as 100 mg per meter cubed over 3 hours every 2 weeks, and up to 10 courses of therapy were evaluated. Patients were allowed to take concomitant antiretrovirals, including protease inhibitors. The median time to response was 49 days, and the median time to treatment failure was 234 days.
Eleven patients died during the study, and four of the deaths were judged Paxene-related, said Harrison. FDA's Kobayashi however, said that seven patients had Paxene-related deaths.
Patients rated their appearance, pain, and mobility significantly improved as a result of Paxene therapy. The panel agreed that Paxene had helped, voting 10-1 that there was a treatment benefit.
Patients responding to 15 questions on a prospective Symptom Distress Scale said that Paxene had significantly improved their quality of life, by reducing pain, increasing mobility and improving their appearance. Harrison also said that 46% of patients had improvement in Karnofsky Performance Status.
Panelists questioned how much of that could be due to the effect of protease inhibitors. Thirty-three patients were taking the drugs, and Harrison said that some improvement might be due to them. On a related issue, the firm did separate studies showing that Paxene did not reduce protease inhibitors' effectiveness.
TEACH plans two fall courses
Project TEACH, the 8-week training program for individuals living with HIV/AIDS focusing on treatment education, communication skills, and activism, has announced two upcoming fall courses, including its first evening course.Graduates receive a certificate of completion as well as a $195 stipend.
TEACH will hold two classes beginning the week of October 13th. The day class is from 10 am - 1 pm, Tuesdays and Thursdays. The evening class is on Mondays and Wednesdays, from 6pm - 8:30 pm, and is reserved for individuals who have work or child care obligations during the day.
TEACH is also doing special outreach for women and transgender applicants for the fall courses.
Interested individuals should contact Agnes Harley or Julie Davids at 215-985-4448.
SUPPORT WE THE PEOPLE THROUGH THE 1997 AIDS WALK!
The annual Philadelphia AIDS Walk takes place on Sunday, October 19, 1997 and is a great opportunity for everyone to raise money to support and fund AIDS services in the Philadelphia region.We The People Living with AIDS/HIV of the Delaware Valley would love it if you would join our team, whether you're a member of We The People, a friend of people living with HIV/AIDS, or just someone who'd like to help.
The AIDS Fund, which sponsors Philadelphia's annual AIDS Walk, last year raised $35,000 for We The People's LifeSavers Fund, which provides emergency assistance to people living with HIV/AIDS, and another $55,000 for our ongoing support services for low-income and homeless people with HIV disease. Over a million dollars was raised for over sixty other critically-needed AIDS services in the Philadelphia region as well.
Won't you help? We're Team #33, and you can register NOW at We The People's Life Center, 425 South Broad Street, or on the web at http://www.CritPath.Org/aidsfund/indreg.html.
And if you can't walk, please make a donation anyway. Checks can be written to the "AIDS Fund" and sent directly to the AIDS Fund office at 1227 Locust Street, Philadelphia, PA 19107. Please remember to mention We The People or Team #33 on your check.
If you do want to walk, the event starts (rain or shine) at the Eakins Oval on the Ben Franklin Parkway in Philadelphia. Sign-in and Opening Ceremonies begin at 9 AM; the Walk starts promptly at 11 AM.
Register NOW to walk and raise money to fight AIDS and support people with HIV or AIDS! For more information, call 215-545-6868 or email aidsfund@critpath.org or wtp@critpath.org.
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