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COMMENTARY |
The authors are with the Program for Appropriate Technology in Health, Seattle, Wash.
Correspondence: Requests for reprints should be sent to Kimberly L. Kelly, MPA, Program for Appropriate Technology in Health, 1455 NW Leary Way, Seattle, WA 98107 (e-mail: kkelly{at}path.org).
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMETHODSRESULTS AND DISCUSSIONRECENT FIELD STUDIES AND...References |
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With more than 60 potential microbicides being assessed in preclinical or clinical trials, most attention has been centered on products intended for topical application, with much less research conducted on the applicators that will be used to deliver the microbicides. However, applicator design relates to safety, efficacy, and acceptability.
As the foundation for a more systematic approach to evaluating and possibly improving designs for topical microbicide applicators, we conducted a literature review and a series of interviews with microbicide developers, trial investigators, and trial sponsors. Our findings indicate that issues concerning applicator safety, reuse, and cost warrant further investigation.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTS AND DISCUSSIONRECENT FIELD STUDIES AND...References |
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According to interviews and literature reviews conducted by the Program for Appropriate Technology in Health (PATH), approximately 6 different applicators are in use in current microbicide trials. Most of these applicators, prefilled with a single dose to reduce dose variability among trial participants, have been adapted from applicators already marketed for other products. The Global Microbicide Project, directed by The Contraceptive Research and Development Program (CONRAD), a sponsor of several microbicide clinical trials, recently conducted physical tests on applicators and polled physicians and consumers regarding the appearance of these products. This work resulted in a prefilled applicator produced by HTI Plastics (Lincoln, Neb) that has been or will be used in evaluations of 8 different microbicides.
The Population Council has used the prefilled Micralax applicator, designed to deliver rectal laxatives, in its trials of the microbicide Carraguard. The Population Council conducted a 2-month study involving 22 women to evaluate the feasibility and acceptability of that applicator as a microbicide/placebo delivery system.1 Finally, one microbicide developer based at Laval University in Canada has patented an applicator specifically for use with his product.
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METHODS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTS AND DISCUSSIONRECENT FIELD STUDIES AND...References |
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for more information about the applicators and products included in each study, along with sample sizes, research settings, and study interventions). This information was used as the basis for a subsequent series of interviews with lead investigators of microbicide clinical, preclinical, and acceptability trials.
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A number of researchers participated in more than one clinical trial, preclinical trial, or both and were able to discuss several trials and corresponding applicators during a single interview. Four researchers discussed information obtained from trials conducted in developing countries. This series of interviews highlighted the importance of more systematic field research on applicators to guide possible design and manufacturing improvements that will address the needs of future microbicide users in resource-poor settings.
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RESULTS AND DISCUSSION |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTS AND DISCUSSIONRECENT FIELD STUDIES AND...References |
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Safety
Given the potential for frequent and sustained use of microbicides and their intended use as a disease prevention method, applicator safety is a paramount consideration in product design. Some researchers noted that the size and shape of applicators as well as methods for insertion may lead to cervical, vaginal, or rectal trauma and commented that additional research should be conducted to provide a more complete understanding of applicator use and its effect on user safety.
Researchers noted that women participating in trials in developing countries expressed concerns about the risks that might occur from washing and storing reusable applicators in unsanitary conditions. These concerns included recontracting sexually transmitted infections, HIV infections, or both; contracting diseases such as cholera; and transmitting sexually transmitted infections, HIV, or both to partners and other family members. In one study, HIV-positive women in the United States reported their belief that cleaning an applicator would be unsanitary and would cause infection.10 Although the literature has not shown any evidence of infections being transmitted via reusable applicators, perceptions of such risks need to be addressed.
The US Food and Drug Administration categorizes vaginal applicators as class I medical devices, meaning that they present minimal potential for harm to the user and are simpler in design than other medical devices. Examples of other class I devices include elastic bandages, examination gloves, and hand-held surgical instruments. Vaginal applicators are exempt from premarket notification, as are most class I devices. Therefore, new stand-alone vaginal applicators can be marketed in the United States without prior Food and Drug Administration clearance.
Reuse
Our literature review indicated that, when asked, US users reported a preference for prefilled disposable applicators.3,5,7 In a survey of Brazilian women, most preferred the concept of a single-use device.4 In a study of women from the United States and South Africa, 44% of the respondents preferred the idea of a single-use applicator as well.10 In interviews, respondents reported that they favored using prefilled single-use applicators in clinical trials to simplify user participation requirements (eliminating the need for women to fill and clean the applicator themselves) and to reduce potential dose variability and user compliance errors associated with reusable applicators.
Outside of clinical research, decisions about reusable versus single-use applicators are intertwined with considerations of safety and cost, as well as convenience, portability, storage, undisclosed use, and disposal. According to 2 of the researchers interviewed, some women in developed countries have voiced concern over adding to environmental waste with disposable applicators, while others prefer single-use, disposable applicators as a result of their convenience. Conversely, 2 other researchers noted that women in developing countries were concerned about privacy of disposal and that they would prefer applicators that could be safely incinerated after use. This issue will have implications for determining the types of materials from which to make applicators.
According to a study conducted in the United States, women who have frequent sexual relations away from their homes found the characteristics of applicator storage and portability to be important.3 Interviews with researchers suggested that women in developing countries may have greater concerns related to both discreet use and storage than women in industrialized countries, who may have more personal privacy. The inconvenience of having to wash an applicator in public places visible to neighbors or family members, as well as lack of accessible and clean water and fear of not being able to adequately clean the applicator, might lead women in developing countries to prefer single-use disposable applicators. Ultimately, both prefilled single-use and reusable applicators are likely to be needed to accommodate different user preferences and markets.
Cost
Cost will probably be one of the key determinants affecting access to microbicide products. Although one study has estimated single-use applicator prices11 and 2 studies have explored what women in developing countries would be willing to pay for a microbicide,12,13 the issue of cost as it relates to single-use versus reusable applicators has not been explored in developing-country populations. While users in some settings may prefer single-use products, the presumed higher cost of single-use applicators is an important decisionmaking factor in resource-poor settings. Nevertheless, alternative designs, less costly raw materials, and streamlined or simplified production processes could reduce manufacturing costs.
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RECENT FIELD STUDIES AND ANALYSES |
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The second study was conducted in the Dominican Republic and South Africa in collaboration with Profamilia and the Reproductive Health Research Unit, respectively. The objective of this acceptability study was to characterize and prioritize women’s needs as they relate to vaginal applicator features. The specific parameters explored were cost, reuse, and perceived applicator safety. In each country, approximately 450 interviews were conducted with randomly sampled participants from selected clinic populations. Actual applicator use was not part of the study.
Conjoint analysis, a quantitative method involving structured surveys and closed-ended interviews, was used to estimate preferences among potential microbicide users in the 2 populations sampled. Conjoint analysis is typically applied in economics and marketing fields; its application to health care interventions is more limited. However, a study applying conjoint analysis to HIV testing provides a good overview of the methodology and how it can be applied to the health field.14 The methodology has also been applied to microbicide research and development.15
In conjunction with these 2 field-based studies, PATH conducted an analysis of different materials and applicator designs in an effort to characterize comparative features in the areas of cost, reuse, and disposal. This analysis assessed biodegradability of materials, effectiveness with which applicators could be cleaned, and alternative materials and fabrication techniques designed to decrease product cost.
Data collection is complete for all studies, and results are expected to be published later in 2004. If results of the safety study, acceptability study, and material/design analysis indicate a need for further refinement or adaptation of applicators for use in resource-poor settings, PATH will first assess existing products marketed by the private sector in both developed and developing countries, where numerous applicator products have been created for a variety of cosmetic and medicinal purposes (e.g., cardboard applicators manufactured for tampon use and medicine delivery). If these products require further research and development, PATH will work with its industry partners to adapt their products in an effort to ensure the availability of low-cost applicators that will meet user needs as well as microbicide delivery requirements.
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Acknowledgments |
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We thank the reviewers for their valuable feedback on the article.
Note. The views expressed in this article do not necessarily reflect the views of the US Agency for International Development.
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Footnotes |
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Accepted for publication February 3, 2004.
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References |
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2. Bentley ME, Morrow KM, Fullem A, et al. Acceptability of a novel vaginal microbicide during a safety trial among low-risk women. Fam Plann Perspect. 2000;32:184–188.[ISI][Medline]
3. Hammett TM, Mason TH, Joanis CL, et al. Acceptability of formulations and application methods for vaginal microbicides among drug-involved women: results of product trials in three cities. Sex Transm Dis. 2000;27:119–126.[ISI][Medline]
4. Hardy E, Jimenez AL, de Padua KS, Zaneveld LJ. Women’s preferences for vaginal antimicrobial contraceptives: III. Choice of a formulation, applicator, and packaging. Contraception. 1998;58:245–249.[Medline]
5. LePage ME, Brown D Jr, Wells J. Patient acceptance of prefilled disposable vaginal applicator. Am J Obstet Gynecol. 1988;158:1006–1008.[Medline]
6. Coggins C, Elias CJ, Atisook R, et al. Women’s preferences regarding the formulation of over-the-counter vaginal spermicides. AIDS. 1998;12:1389–1391.[Medline]
7. Gross M, Celum CL, Tabet SR, Kelly CW, Coletti AS, Chesney MA. Acceptability of a bioadhesive nonoxynol-9 gel delivered by an applicator as a rectal microbicide. Sex Transm Dis. 1999;26:572–578.[Medline]
8. Barnhart KT, Pretorius ES, Stolpen A, Malamud D. Distribution of topical medication in the human vagina as imaged by magnetic resonance imaging. Fertil Steril. 2001;76:189–195.[Medline]
9. Barnhart KT, Stolpen A, Pretorius ES, Malamud D. Distribution of a spermicide containing nonoxynol-9 in the vaginal canal and the upper female reproductive tract. Hum Reprod. 2001;16:1151–1154.
10. Morrow K, Rosen R, Richter L, et al. The acceptability of an investigational vaginal microbicide, PRO 2000 Gel, among women in a phase I clinical trial. J Womens Health. 2003;12:655–666.
11. The Science of Microbicides: Accelerating Development. New York, NY: Rockefeller Foundation; 2002:74.
12. Hardy E, de Padua KS, Osis MJ, Jimenez AL, Zaneveld LJ. Women’s preferences for vaginal antimicrobial contraceptives: IV. Attributes of a formulation that would protect from STD/AIDS. Contraception. 1998;58:251–255.[Medline]
13. Hill R, Ryan J, Stone A, Fransen L. Vaginal microbicides for the prevention of HIV/AIDS: assessment of the potential market. Int J Pharm Med. 2000;14:271–278.
14. Phillips KA, Maddala T, Johnson FR. Measuring preferences for health care interventions using conjoint analysis: an application to HIV testing. Health Serv Res. 2002;37:1681–1705.[ISI][Medline]
15. Holt YB, Ngo L, Harrison P, et al. The market potential for microbicides: young US women. In: Programs and abstracts of the Microbicides 2002 conference, May 2002, Antwerp, Belgium. Abstract C-284.
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