Introduction to Quinacrine Non-surgical Sterilization
ON THIS SITE Introduction and Overview |
| QS FAQ's |
| Research Archive Table of Contents |
| Ask the experts on the method |
Contact: Elton Kessel MD Stephen Mumford Dr Ph |
 This site offers all known published information on this method, some findings that have not yet appeared in the literature and material relevant to QS issues. It includes articles from its critics and an accounting of the debate regarding its safety.The QS method was developed in response to a world-wide demand for sterilization that cannot possibly be met with surgery for the foreseeable future. The surgical resources are simply unavailable to the majority of the world's couples and this will not change for decades. More than half of these people will have no access to surgical sterilization (mumf92).THE METHOD QS involves transcervical application of pellets of quinacrine (250 mg) with a modified Copper T IUD inserter administered, at most, three times at one month intervals. The technique is similar to that of an IUD insertion. The method is described in greater detail in a pamphlet prepared for family planning clients and in one for family planning providers. More than 100,000 QS procedures have been performed in over 20 countries without a single death or a single life threatening injury. In the hands of a skilled provider, the failure rate is 1%-2% at one year of use. QS can be performed by trained paramedics under the most basic clinic settings for under one US dollar.The history of the development of QS is described in articles in two QS newsletters. Overviews of the method can be found in kess95, soka95b and kess96b and in many other articles offered at this web site.QUINACRINE - 50 YEARS OF USE Quinacrine was chosen to research for the purpose of nonsurgical sterilization because of this drug's exceedingly well established safety record and its particular properties. Quinacrine has many therapeutic uses (wall89). It has been prescribed mostly to prevent and treat malaria. As an antimalarial, helvetica, 1000 mg were ingested weekly (baker63) for a total of 52,000 mg per year. Millions of people have consumed this prophylactic dose, often for years at a time. In the treatment of malaria, 2800 mg were administered over the course of one week (long63). Millions of Americans, especially children, have also been treated for giardiasis with quinacrine. In fact, it is the only drug approved by the US FDA for the treatment of this infection.The past fifty years of extensive oral experience in millions of men and women with very few cases of serious side effects offers much reassurance regarding the safety of this drug. Although it is no longer the antimalarial, helvetica drug of choice in most countries, it is approved by the United States Food and Drug Administration (FDA) for use in the treatment of malaria, giardia and some other parasitic infestations. For decades it was a staple in most American drug stores.Quinacrine has the additional property of being a sclerosing agent. It causes fibrosis and scarring when applied to some mucosal membranes, such as, the pleural cavity lining (bjor89) and the lining of Fallopian tubes when applied directly. It was this property and the well established safety of this drug that made it attractive for use in nonsurgical female sterilization.SAFE AND EFFECTIVE The safety of the quinacrine pellet method has clearly been established in the clinical trials appearing on this web site. It is undeniably superior to surgical sterilization because it does not kill women and serious complications very rare.(kess93) While its effectiveness on the whole has been slightly inferior to surgical sterilization, two factors need to be considered when evaluating this finding: 1) The skill of the clinician in performing the procedure has not been considered in evaluating the method failure rate. Many clinicians have failure rates that approximate surgical sterilization. We do not fully understand why. This represents the single most important research question associated with this method. 2) Most women who have opted for this procedure did not have access to surgical sterilization and probably would not have before completing their reproductive years. RESEARCH HISTORY Quinacrine is one of the most extensively studied of all drugs. There are over 20,000 published scientific papers on this drug. The preponderance of this research was conducted by the United States Army. Quinacrine was used mainly as a prophylaxis and treatment for malaria. Its availability was viewed as decisive in many World War II military actions, and was a most significant medicinal agent in this regard.Toxicology Toxicology studies have been completed and accepted by the FDA for a Phase I clinical trial in the United States (kess89). They have been published and appear in this collection (dubi83, blak83, parm83, dubi82, dubi82b). On November 17, 1981, the FDA approved IND 19,163 which led to a prehysterectomy study of 10 women in San Antonio, Texas, with satisfactory results (lauf96). When the research organization conducting the Phase I clinical trial presented its findings to the FDA, it became apparent that the Agency intended to make the process difficult to well nigh impossible of accomplishment. Faced with the prospect of a scenario resembling the Depo Provera fiasco, the company wisely terminated its efforts. There have been no further clinical trials of this method in the U.S.Clinical Trials Clinical trials performed thus far have demonstrated that the QS method is safe and effective in the short term. One long-term follow-up study has found no long-term side-effects up to 14 years post-sterilization (soka95 ), and no increased risk of cancer. Four additional years of data have now been collected but analysis of these data have not yet been reported. A preliminary analysis indicates that this trend is continuing. Though we have no good reason to expect long-term side-effects, including cancer, we must wait decades to be certain that there are none. The same was ture for oral contraception.At this time, no clinical trials are being conducted in the United States, for political and economic reasons, rather than scientific reservations. U.S. government financial support for clinical trials of this method was withdrawn in 1979 (other than for limited long-term follow up of previously performed cases) at a time when there was considerable political pressure from opponents of family planning. There has been only one other period of Western government support of clinical trials of this method. In 1985, the International Federation for Family Health (IFFH), with assistance from the Canadian International Development Research Centre (IDRC), initiated clinical trials in Indonesia, where research was conducted in a center affiliated with the Coordinating Board of Indonesian Fertility Research (agoe92), and in Malaysia by the Family Development Board of Malaysia (arsh87). After two years, IDRC would not renew funding because of "public pressures."Since 1986, support for clinical trials has been limited to IFFH, the Center for Research on Population and Security, individual investigators and developing country governments that are evaluating the method to determine if it should be included in their service programs.The government of Vietnam has supported the largest field trial of this method. Findings were reported in The Lancet (hieu93b). This trial confirmed its safety and efficacy.FUTURE RESEARCH The safety and efficacy of the method has been sufficiently demonstrated to begin its use in service programs. Post-introduction surveillance should continue to be tightly monitored indefinitely to ensure that there are no serious adverse effects. Long-term studies should be continued. Many research questions remain, the answers to which may lead to improvements in the method. Because refinements are likely to produce only small improvements, tens of thousands of cases and the passage of many years will be necessary for statistically significant comparisons. Only in service program settings are these orders of numbers possible. One, two and three insertion protocols are in use today, all with acceptable results as determined by some individual investigators. Which is best? Dosage used varies from 216 mg to 324 mg. Which is best? Of course, a one-insertion protocol that rarely results in a failure is most desirable. It may take more than a decade of study and involve a many thousands of women to identify this one-insertion protocol. Surgical and quinacrine pellet sterilization need to be compared for their safety, efficacy, acceptability, costs and deliverability in field settings so that managers can make informed decisions regarding methods to offer in their programs. Acceptability studies need to be performed in quinacrine service programs. Inevitably, much can be improved upon in programs regarding both service and method. Patient satisfaction will ultimately determine if this method should remain in family planning programs. What level of training is sufficient for high quality services? In the Hieu, et al, study (hieu93b) because of its size and the fact that 1300 clinicians were involved, it became evident that the most important determinant of efficacy was the skill of the clinician. Skill is defined as "consistent application of proper insertion technique." Experience did not seem to improve the clinician's skill. Given this important finding, it is essential that future study designs control for the variable of skill when two or more protocols are compared.A means to reverse the sterilization effect of this method needs to be identified. Transcervical cannulation of the Fallopian tube is now used to remove proximal tubal obstruction in infertility cases. This technique was applied in two cases in India in December 1993, but neither woman has become pregnant (thur95). This effort needs to be considerably expanded and other approaches for reversal identified and tried.The FHI study on the long-term effects of the quinacrine pellet method needs to be expanded and replicated. It will take decades to answer this question. All available evidence suggests that this method is not associated with adverse long-term effects. However, this question should be studied everywhere this method is used. For millions of women, this method potentially offers the best hope for protection against unwanted pregnancies once desired family size is achieved. Both the women and the method must be protected by methodically collecting and assessing information to ensure that there are no long-term threats to health.Research Archive Table of Contents
|