Title: Estimating the value of future research to improve guidelines on thromboprophylaxis for women during pregnancy and after delivery
Funder: Department of Health and Social Care

Abstract: AIM_x000D_ To use what we know already from existing research to work out what further research should be done to improve outcomes for women at risk of blood clots during pregnancy and in the early weeks after pregnancy._x000D_ _x000D_ BACKGROUND_x000D_ Women who are pregnant or who have delivered a baby in the previous 6 weeks are at increased risk of blood clots that can cause serious illness or death. Small doses of blood thinning drugs can reduce the risk of blood clots but they also slightly increase the risk of bleeding. Currently whether or not a woman is offered blood thinning drugs to prevent blood clots depends on whether they are considered to have a high, medium or low risk of blood clots. This is worked out by their doctor based on factors such as their age, their previous illnesses, and for women who have given birth, the type of delivery they had. The tool used most often by UK doctors to decide if a patient is at high risk is one published by the Royal College of Obstetricians and Gynaecologists, but there are other alternative tools that could be used and each tool would select a different group of women to receive blood thinning drugs. We do not currently know whether we would be better to use an alternative risk assessment tool that results in either fewer or more women receiving blood thinning drugs. In addition, although there have been many clinical trials which show that blood thinning drugs reduce the risk of blood clots in other high risk groups, such as patients having operations, there have been fewer clinical trials of these drugs in women who are pregnant or who have recently delivered. Therefore, further research would be useful to help doctors decide which women should receive blood thinning drugs._x000D_ _x000D_ DESIGN & METHODS_x000D_ The project will involve reviewing and bringing together all the existing research about this topic into a mathematical model. This model will allow us to explore whether it would be better to offer blood thinning drugs to more women to prevent more blood clots or whether it would be better to offer it to fewer women to minimise the numbers being exposed to an increased risk of bleeding. We will also use the model to work out where we currently lack the information we need to make the best decisions about using blood thinning drugs and what further research would be most valuable and cost efficient. We will then hold a workshop with women, to help us decide whether the future research studies suggested by the modelling would be acceptable to women and would capture the outcomes that matter to them. We would invite women to the workshop who have had the experience of being offered blood thinning drugs or who have experienced a blood clot during pregnancy or in the early weeks after pregnancy. We will also conduct a survey of doctors to ask if the proposed research will be practical to conduct._x000D_ _x000D_ PATIENT & PUBLIC INVOLVEMENT_x000D_ We have a patient member as part of the project team who will help us develop and undertake this project. She will also act as a link to a broader community of patients through Thrombosis UK who we have worked with on two previous projects._x000D_ _x000D_ DISSEMINATION_x000D_ This project is designed to help research funders decide what research to fund to improve outcomes for women at risk of pregnancy-related blood clots. A report on our research will be shared with research funders and accessible summaries of our findings will be shared with patient organisations and doctors who care for pregnant women.

Lay abstract: RESEARCH QUESTION_x000D_ What is the value of undertaking a study to determine the clinical and cost-effectiveness of risk stratification tools for the prediction of venous thromboembolism (VTE) and appropriate provision of thromboprophylaxis for women in pregnancy and after delivery?_x000D_ BACKGROUND_x000D_ Pharmacological prophylaxis to prevent VTE is currently recommended for women who are deemed to be at high risk of VTE during pregnancy or in the 6 weeks after delivery. The decision to provide prophylaxis involves weighing the benefits, harms and costs, which will vary according to the individual’s VTE risk. It is unclear whether the current risk stratification approach could be improved by further research. _x000D_ AIMS AND OBJECTIVES_x000D_ The aim of the research project is to determine whether further primary research is worthwhile to inform NHS practice on the use of risk stratification tools for the prediction of VTE and appropriate provision of thromboprophylaxis for women in pregnancy and in the puerperium. The specific objectives will be;_x000D_ 1) To estimate the expected costs, health benefits (quality-adjusted life-years) and incremental net monetary benefit of providing thromboprophylaxis using current and alternative risk stratification tools and to quantify the uncertainty around those estimates, given current evidence _x000D_ 2) To determine which factors are the most important drivers of uncertainty when trying to determine the optimal risk-based thromboprophylaxis strategy in this population_x000D_ 3) To identify one or more potential future studies to gather additional evidence that would reduce the current decision uncertainty, whilst being feasible and acceptable to patients and clinicians._x000D_ 4) To evaluate the value of the potential future research studies in terms of the net health benefits to patients and the cost of the research._x000D_ METHODS_x000D_ A decision analytic model will be developed which will be informed by reviews of the existing literature. This model will be used to determine which factors are the most important drivers of uncertainty using expected value of perfect information analysis. Qualitative research, in the form of workshops with patients and a survey of clinicians, will then be undertaken to identify one or more potential future studies that could be conducted to gather additional evidence to reduce the current decision uncertainty. Expected value of sample information analysis will then be used to evaluate the value of the potential future research studies in terms of the net health benefits to patients and the cost of the research_x000D_ TIMELINES FOR DELIVERY_x000D_ The project will take place over 15 months with cost-effectiveness modelling (including rapid reviews of parameters) and expected value of perfect information analysis in months 1 to 7, qualitative work to inform potential study designs in months 8 to 10, expected value of sample information analysis in months 11 to 12 and write up and dissemination in months 13 to 15. _x000D_ ANTICIPATED IMPACT AND DISSEMINATION_x000D_ We anticipate that this project will inform the funding of future research studies and may also inform clinical guideline updates. We will share our findings and research recommendations with UK research funders and guideline developers. We will also disseminate professional and plain language summaries to relevant clinical, public and patient representative organisations so they are able to make an evidence-based case for further research or changes to current clinical practice.

Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;7.3 MANAGEMENT AND DECISION MAKING
Health categories: CARDIOVASCULAR;REPRODUCTIVE HEALTH AND CHILDBIRTH