Using research to advocate and implement policy change
As the Mwanza STD trial demonstrates, it is essential that researchers consider the potential policy implications of their findings, instead of focusing solely on the technical aspects. Researchers need to be aware of the contexts in which research and policy interact, and to understand how changing political contexts affect the way research outcomes are received if they are to increase the chances of their research findings having a stronger impact. The Mwanza trial, carried out in Tanzania in 1991–94, demonstrated the effectiveness of improved treatment for STDs in preventing HIV infection. Subsequently, STD control services, especially syndromic management, were commonly adopted as one of the main components of HIV prevention programmes, along with education and condom promotion. However, what made the transition from research to policy possible was that the policy environment at the time was favourable, many researchers and policymakers had acknowledged that AIDS was a serious problem, and they were looking for effective strategies and solutions. There was also close contact and a sense of shared ownership between the researchers, the government of Tanzania, donors and NGOs during the study period. This was further facilitated by long-standing connections between key researchers and policymakers, who were linked by both conviction and interest throughout, not just at the post-research stage. Finally, the complex epidemiological data produced were reduced to a single conclusion, and the trial itself became known mainly for one particular statistical result—the reduction by 42% in HIV infection in the intervention site as compared with control areas. This had the advantage of being easily understood and facilitated advocacy efforts. However, it also raised false expectations that the findings were applicable to all other demographic, epidemiological and behavioural contexts.1
Philpott A, Maher D, Grosskurth H. Translating HIV/AIDS research findings into policy: lessons from a case study of the “Mwanza trial”. Health Policy and Planning 2002;17(2):196–201.
Mifepristone may also treat serious health conditions
The approval of mifepristone for medical abortion by the US Food and Drug Administration (FDA) in 1998 boosted research into its potential other uses. The drug's therapeutic potential stems from its ability to act against the hormones cortisol, progestogen and oestrogen. Cortisol is essential to regulating blood pressure and metabolism, and helps the body cope with stress. Cortisol levels are normally high in athletes and in women in the last few months of pregnancy, and abnormally high in people with depression, alcoholism, malnutrition and panic attacks. Cortisol may also play a role in the reproduction of HIV; scientists have shown that blocking cortisol in cells in vitro can reduce the ability of HIV to multiply and infect more cells. Mifepristone may also relieve suicidal depression, and scientists are testing whether it can help to slow cognitive decline in Alzheimer's patients. The hormone progestogen is essential for sustaining a pregnancy, thus, the effectiveness of mifepristone for abortion. But since progestogen and oestrogen influence other reproductive processes and organs in men as well as women, mifepristone may also be useful for treating uterine fibroids, endometriosis, and certain breast, cervical, ovarian and prostate cancers.1
McCullough M. “Abortion pill” shows promise for diseases. Knight Ridder/Tribune News Service, 27 September 2002
Switching off the genes that trigger cervical cancer
Over 90% of human cervical cancers are positive for human papillomavirus (HPV) and two genes from the virus are known to drive the abnormal cell proliferation that occurs. Using short interfering RNA sequences which block the messages from these genes, researchers have successfully halted viral gene expression in cells and subsequent cell proliferation. Silencing one of the genes allowed the cells some limited growth, whereas silencing the other completely stopped cell proliferation and resulted in cell death by apoptosis, a normal mechanism which fails to work with cancer cells, which proliferate without dying. The technique had no effect on cells not infected with HPV. This is the first demonstration that it may be possible to switch off the cancer-causing effects induced by HPV without necessarily interfering with normal cell development.1
Jiang M, Milner J. Selective silencing of viral gene expression in HPV-positive human cervical carcinoma cells treated with siRNA, a primer of RNA interference. Oncogene 2002;21(39):6041–48. [Medline abstract]
Association between parity, oral contraceptive use and cervical cancer
Pooling of data by the International Agency for Research on Cancer from case-control studies of invasive cervical cancer (eight studies) and carcinoma in-situ (two studies) from four continents found that high parity and long-term use of hormonal contraception increased the risk of squamous-cell carcinoma of the cervix among women testing positive for human papillomavirus (HPV), consistent with previous studies. The decline in parity in most countries might therefore partly explain reductions in cervical cancer recently seen. High parity has long been suspected of being associated with an increased risk of cervical cancer, but previous analyses of this association did not take HPV into account. The odds ratio for seven full-term pregnancies or more was 3.8 compared with nulliparous women, and 2.3 compared with women who had had one or two full-term pregnancies. There was no significant association between risk of adenocarcinoma and adenosquamous carcinoma and number of full-term pregnancies. Hormonal contraceptive use for fewer than five years did not increase risk, but women reporting use of hormonal contraceptives for 5–9 years had 2.8 times the risk of women who had never used them. The relative-risk estimate was even higher (4.0) for those who had used hormonal contraceptives for 10 years or longer. Perhaps the chief importance of this new analysis is the demonstration that these associations are not due to any confounding effect of HPV infection, and adjustments for sexual behaviour provided only partial reassurance about confounding by HPV. Among the controls, multiparous women and those who had taken oral contraceptives were not more likely than others to be carriers of HPV DNA.
If these results are confirmed, there will be wider acceptance that high parity and long-term use of oral contraceptives can act as co-factors in the genesis of cervical cancer. The lack of association of these factors with the prevalence of HPV infection would suggest that each acts not by enhancing the acquisition or persistence of HPV infection, but rather by promoting progression to CIN and invasive cervical cancer. Although many case-control and cohort studies not restricted to women with HPV infection have shown an association between long-term oral contraception and risk of cervical cancer, the relative-risk estimates have generally been lower.
However, despite the importance of the IARC analysis, it could have overestimated the risk associated with long-term oral contraception for a number of reasons. Any causal relation between long-term oral contraception and cervical cancer would be most important in the developing world, where cervical cancer is common and few women have access to high-quality cytological screening. From a public health viewpoint, a key question is the extent to which effects persist after women stop taking oral contraceptives. There is now a need to bring together all the relevant data, to quantify any effects, and to assess how these might shift the balance of benefits and risk of oral contraception. The WHO has commissioned such work, to prepare the ground for a full assessment. For nearly two decades, concerns about oral contraceptives and cancer were focused mainly on breast cancer, with the eventual outcome of studies reassuring. Any relation with cervical cancer is also important to determine.1–3
Skegg DCG. Oral contraceptives, parity, and cervical cancer. Lancet 2002;359:1080–81.
Moreno V, Bosch FX, Muñoz N, et al. Effect of oral contraceptives on risk of cervical cancer in women with human papillomavirus infection: the IARC multicentric case-control study. Lancet 2002;359:1085–95.
Muñoz N, Franceschi S, Bosetti C, et al. Role of parity and human papillomavirus in cervical cancer: the IARC multicentric case-control study. Lancet 2002; 359:1093–101.
No link found between ovarian stimulation for infertility treatment and ovarian cancer
Concerns have been expressed about the long-term health implications of ovarian stimulation treatment for infertility, and questions raised about whether it would increase the risk of breast, uterine and ovarian cancers. A recent study found no evidence for a link between ovarian stimulation as part of treatment for infertility and increased risk for ovarian cancer.1
MacLean AB. Epithelial ovarian cancer and infertility treatment. Journal of Obstetrics and Gynaecology 2002;22(1):7–8.
Gold standard for sperm fertility
In a major step towards understanding male infertility, scientists have developed a “gold standard” for fertile sperm. By analysing the complex genetic fingerprint of sperm cells, they identified about 3,000 individual messenger RNA for fertile men, thus creating a genetic benchmark for comparison with sperm of infertile men. In the UK, the underlying cause of infertility remains unknown in about two-thirds of men who undergo infertility assessment. Future analysis could identify the defective genes that contribute to infertility and show whether some of the messenger RNA in healthy sperm could contribute to viability after fertilisation. The fingerprints might also help to understand the process of sperm production and any environmental effects on sperm and sperm counts.1
Researchers set standard for male fertility. University of Leeds Press Office. 5 September 2002.
No clear message about hormone replacement therapy
Work on the aetiology of coronary heart disease in women has been dominated by the idea that oestrogen has a protective role in pre-menopausal women, and that hormone replacement should maintain that protection. However, the evidence against this seems to be mounting. Some analyses of mortality data suggest that the narrowing of the gap between men and post-menopausal women is more due to a deceleration in death rates in men than to changes in death rates in women.1 A US study comparing the effects of long-term, combined oestrogen + progestogen to oestrogen alone was halted after the discovery of a small but increased risk of cardiovascular disease, as well as breast cancer, blood clots and stroke, in women taking the combined regime.2 Because of the data from the US trial, a major UK trial has also been stopped early, on the grounds that a large reduction in the risk of coronary heart disease now seems unlikely.3
Long-term HRT does have some clearly documented benefits, including a decrease in osteoporosis and bowel cancers.2 Now researchers are looking at its role in preventing dementia. Results vary, with some researchers failing to detect any benefit of taking oestrogen,4 while others claim that long term HRT may protect women from Alzheimer’s disease.5 With such conflicting evidence and varying methodologies, much of this research is open to alternative interpretation. Articles from respected journals are now giving conflicting opinions, with the BMJ advising long-term HRT use for prevention of osteoporosis,6 and JAMA advising against oestrogen or progestogen for chronic disease.7 Many women are uncertain what to do.
Lawlor DA, Ebrahim S, Smith GD. Role of endogenous oestrogen in aetiology of coronary heart disease: analysis of age related trends in coronary heart disease and breast cancer in England and Wales and Japan. BMJ 2002;235:311–12.
Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA 2002;288:321–33.
White C. Second long term HRT trial stopped early. BMJ 2002;325:987.
Grady D, Herrinton D, Bittner V, et al. Cardiovascular disease outcomes during 6.8 years of hormone therapy: heart and estrogen–progestin replacement study follow-up (HERS II). JAMA 2002;288:49–57.
Zandi PP, Carlson MC, Plassman BL, et al. Hormone replacement therapy and incidence of Alzheimer disease in older women: the Cache County Study. JAMA 2002;288:2123–29.
Stevenson JC, Whitehead MI. Hormone replacement therapy. BMJ 2002;325:113–14.
Fletcher SW, Colditz GA. Failure of estrogen plus progestin therapy for prevention. JAMA 2002;288:366–68.
Developing country researchers poorly represented in leading medical journals
A survey of five international peer-reviewed medical journals—Lancet, BMJ, New England Journal of Medicine, JAMA, and Annals of Internal Medicine—found that the proportion of space given to articles about developing countries is low. Relatively few articles were specifically relevant to health in Eastern Europe, South/Central America, the Caribbean, North Africa or the Middle East. Infectious diseases, particularly HIV/AIDS, malaria and tuberculosis, were common topics. Most authors, especially for editorials and commentaries, were from developed countries, although the majority of research articles were co-authored by developed and developing country researchers. This suggests that a North–South imbalance exists in the production and dissemination of knowledge, and that a developing country researcher's best chances of getting published in one of these journals is only through collaborating with a developed country scientist.1
Obuaya C. Reporting of research and health issues relevant to resource-poor countries in high-impact medical journals. European Science Editing 2002;28(3):72–77.
Figure 1 School, Khodjely City, Uzbekistan, 1997
