Oral Contraceptive Use for the Primary Prevention of Ovarian Cancer: Review Protocol

Ovarian Cancer Prevention
Full Title: Oral Contraceptive Use for the Primary Prevention of Ovarian Cancer
Expected Release Date: 2011

Contents
Background and Objectives for the Systematic Review
The Key Questions
Analytic Framework
Methods
References
Definition of Terms
Summary of Protocol Amendments



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Background and Objectives for the Systematic Review

Although ovarian cancer is only the eighth most common cancer in women (annual age-adjusted incidence 12.3/100,000), it is the fifth leading cause of cancer deaths (8.2/100,000).1 Given current age-specific incidence data and U.S. Census demographic projections, we estimate that the annual number of new ovarian cancer cases will almost double (to 40,000) over the next 25 years as the baby boom generation reaches the ages of highest risk.2 The high mortality rate has been largely attributed to the fact that ovarian cancer typically presents at a much later stage than other common cancers.1 This in turn has led to intense interest in developing screening strategies, with disappointing results to date, especially in terms of mortality reduction.3-9 However, several factors limit the success of screening for this disease: the cause of ovarian cancer is unknown; there is no definitive preinvasive stage; and, most important, there is no physical barrier to impede rapid spread from the surface of the ovary (FIGO Stage I) to the upper abdomen (FIGO Stage III).10 The possibility of rapid spread from the ovary means that many cancers identified at Stage I may represent a subgroup of less aggressive tumors rather than a necessary first step in the development of all tumors. If this is the case, screening, which is more likely to identify slower growing tumors, may have only a limited impact on overall ovarian cancer mortality, as suggested by previous work from our group.11

Given that the potential effectiveness of screening for reducing morbidity and mortality from ovarian cancer is limited by the underlying biology of the disease, alternative strategies, including both more efficacious and less toxic therapies after diagnosis and primary prevention, need to be considered and evaluated. Oral contraceptives (OCs) represent the most promising primary prevention strategy for ovarian cancer. Several studies suggest a protective effect of OCs on ovarian cancer risk, with a reduction in risk of up to 50 percent with long-term use.12,13 OCs have both other noncontraceptive health benefits14,15 and harms, including premature death.16-19 The combination of a systematic review and decision analytic modeling will allow us to estimate the tradeoffs between these harms and benefits for the overall population and for individual women, accounting for the potential influence of other factors such as OC formulation and intervening pregnancies.


The Key Questions

The draft key questions (KQs) were distributed to the Technical Expert Panel (TEP) members for review and discussion during a teleconference held with the Evidence-based Practice Center (EPC) research team, Agency for Healthcare Research and Quality (AHRQ) Task Order Officers, and partner organization representatives on January 18, 2011. The TEP members accepted the key questions as written, with no suggestions for revision. KQ 6 was subsequently revised for clarity after further discussion with AHRQ. The TEP members recommended ranking the candidate outcomes for consideration according to the potential impact OC use might have on them. This process is described further in section IV F.

•KQ 1: What is the effectiveness of combined (estrogen and progestin containing) and progestin-only oral contraceptives (OCs) for reducing the risk of ovarian cancer?
•KQ 2: Do specifics of OC use (e.g., dose/formulation, age at initiation, duration of use) affect the relative risk of developing ovarian cancer?
•KQ 3: Does the use of OCs by specific populations of women (e.g., those defined by age, family history of breast and ovarian cancer, BRCA1/BRCA2 mutation status, parity) affect the relative risk of developing ovarian cancer?
•KQ 4: Aside from pregnancy prevention, are there other benefits of OC use (e.g., reducing the risks of conditions such as benign ovarian cysts, endometriosis, endometrial hyperplasia, endometrial cancer, dysmenorrhea, acne, colorectal cancer, dysfunctional uterine bleeding, or premenstrual dysphoric disorder)?
•KQ 5: What are the harms of OC use, including, but not necessarily limited to, breast cancer incidence, cervical cancer incidence, venous thromboembolic disease, neurological conditions, stroke, or cardiovascular disease? How do these harms vary by dose or formulation, duration of use, or specific population?
•KQ 6: Based on the comprehensive literature review, what are the benefits and harms from the use of OCs to reduce the incidence of ovarian cancer for specific populations? Based on the decision model, what is the estimated effect of these benefits and harms on life expectancy and quality-adjusted life expectancy?
•KQ 7: Based on the systematic review and decision model, what research gaps need to be filled to better understand whether OCs are effective for primary prevention of ovarian cancer?


full-text (large size):
Oral Contraceptive Use for the Primary Prevention of Ovarian Cancer: Review Protocol


Summary of Protocol Amendments

In the event of protocol amendments, the date of each amendment will be accompanied by a description of the change and the rationale.

Review of Key Questions

Key questions submitted by the Centers for Disease Control and Prevention (CDC) partner in this systematic review will be reviewed and refined as needed by the EPC with input from the TEP to assure that the questions are specific and explicit about what information is being reviewed. The TEP will be drawn from individuals with expertise in ovarian cancer biology and epidemiology, hormonal contraception, and women's health. We anticipate that many of these experts will represent stakeholder organizations, including professional organizations, patient groups, advocacy groups, and Federal agencies.

Technical Expert Panel (TEP)

Technical experts comprise a multidisciplinary group of clinical, content, and methodological experts who provide input in defining populations, interventions, comparisons, or outcomes as well as identifying particular studies or databases to search. They are selected to provide broad expertise and perspectives specific to the topic under development. Divergent and conflicted opinions are common and perceived as health scientific discourse that results in a thoughtful, relevant systematic review. Therefore study questions, design and/or methodological approaches do not necessarily represent the views of individual technical and content experts. Technical experts provide information to the EPC to identify literature search strategies and recommend approaches to specific issues as requested by the EPC. Technical experts do not do analysis of any kind nor contribute to the writing of the report and have not reviewed the report, except as given the opportunity to do so through the public review mechanism.

Technical experts must disclose any financial conflicts of interest greater than $10,000 and any other relevant business or professional conflicts of interest. Because of their unique clinical or content expertise, individuals are invited to serve as technical experts and those who present with potential conflicts may be retained. The Task Order Officer (TOO) and the EPC work to balance, manage, or mitigate any potential conflicts of interest identified.

Peer Review (Standard Language)

Peer reviewers are invited to provide written comments on the draft report based on their clinical, content, or methodological expertise. Peer review comments on the preliminary draft of the report are considered by the EPC in preparation of the final draft of the report. Peer reviewers do not participate in writing or editing of the final report or other products. The synthesis of the scientific literature presented in the final report does not necessarily represent the views of individual reviewers. The dispositions of the peer review comments are documented and will, for Comparative Effectiveness Reviews (CERs) and technical briefs, be published 3 months after the publication of the evidence report.

Potential reviewers must disclose any financial conflicts of interest greater than $10,000 and any other relevant business or professional conflicts of interest. Invited Peer Reviewers may not have any financial conflict of interest greater than $10,000. Peer reviewers who disclose potential business or professional conflicts of interest may submit comments on draft reports through the public comment mechanism.


Current as of March 2011


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Internet Citation:

Oral Contraceptive Use for the Primary Prevention of Ovarian Cancer, Review Protocol. Agency for Healthcare Research and Quality, Rockville, MD.
http://www.ahrq.gov/clinic/tp/ovarcantp.htm
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