Quality of life assumptions determine which cervical cancer screening strategies are cost-effective.

Quality-adjusted life years are used in cost-effectiveness analyses (CEAs). To calculate QALYs, a "utility" (0-1) is used for each health state induced or prevented by the intervention. We aimed to estimate the impact of quality of life (QoL) assumptions (utilities and durations of health states) on CEAs of cervical cancer screening. To do so, 12 alternative sets of utility assumptions were retrieved from published cervical cancer screening CEAs. Two additional sets were based on empirical QoL data that were integrally obtained through two different measures (SF-6D and EQ-5D) from eight groups of women (total n = 3,087), from invitation for screening to diagnosis with cervical cancer. Per utility set we calculated the number of quality-adjusted days lost (QADL) for each relevant health state in cervical cancer screening, by multiplying the study-specific assumed disutilities (i.e., 1-utility) with study-specific durations of the loss in QoL, resulting in 14 "QADL-sets." With microsimulation model MISCAN we calculated cost-effectiveness of 342 alternative screening programs (varying in primary screening test [Human Papillomavirus (HPV) vs. cytology], starting ages, and screening interval) for each of the 14 QADL-sets. Utilities used in CEAs appeared to differ largely. We found that ten QADL-sets from the literature resulted in HPV and two in cytology as preferred primary test. The SF-6D empirical QADL-set resulted in cytology and the EQ-5D one in HPV as preferred primary test. In conclusion, assumed utilities and health state durations determine cost-effectiveness of cervical cancer screening. Also, the measure used to empirically assess utilities can be crucial for CEA conclusions.

Effect of Cervical Cancer Screening Programs on Preterm Birth: A Decision and Cost-Effectiveness Analysis.

OBJECTIVE: To assess the effect of age at initiation and interval of cervical cancer screening in women of reproductive age on the risk of future preterm birth and subsequent adverse neonatal outcome relative to maternal life-years gained and cost of both screening and preterm birth. METHODS: In this decision and cost-effectiveness analysis, we compared eight cytology-based screening programs varying in age of onset (21, 24, 25, 27, or 30 years) and screening interval (3 or 5 years) in a fictive cohort of 100,000 women. We used the microsimulation screening analysis model to estimate number of cervical intraepithelial neoplasia diagnoses, large loop excisions of the transformation zone (LLETZs), life-years gained, cervical cancer cases, deaths, and costs of screening and treatment. We used the number of LLETZs to calculate additional preterm births, subsequent neonatal morbidity, mortality, and associated costs. RESULTS: The number of LLETZs per 100,000 women varied from 9,612 for the most intensive screening (every 3 years from age 21 years) to 4,646 for the least intensive screening (every 5 years from age 30 years). Compared with the least intensive program, the most intensive program increased maternal life-years gained by 9% (10,728 compared with 9,839), decreased cervical cancer cases by 67% (52 compared with 158), and cervical cancer deaths by 75% (four compared with 16) at the expense of 250% (158 compared with 45) more preterm births and 320% (four compared with one) more neonatal deaths while increasing total costs by $55 million ($77 compared with $23 million). The number of maternal life-years gained per additional preterm birth varied from 68 to 258 with subsequent total costs per maternal life-years gained of $7,212 and $2,329. CONCLUSION: Cervical cancer screening every 3 years and subsequent treatment in women aged younger than 30 years yield limited life-years but may have substantial perinatal adverse effects. Consequently, women who plan to have children may benefit from a more cautious screening approach, taking into account their risk for both cancer and preterm birth.

A revised prediction model for natural conception.

One of the aims in reproductive medicine is to differentiate between couples that have favourable chances of conceiving naturally and those that do not. Since the development of the prediction model of Hunault, characteristics of the subfertile population have changed. The objective of this analysis was to assess whether additional predictors can refine the Hunault model and extend its applicability. Consecutive subfertile couples with unexplained and mild male subfertility presenting in fertility clinics were asked to participate in a prospective cohort study. We constructed a multivariable prediction model with the predictors from the Hunault model and new potential predictors. The primary outcome, natural conception leading to an ongoing pregnancy, was observed in 1053 women of the 5184 included couples (20%). All predictors of the Hunault model were selected into the revised model plus an additional seven (woman's body mass index, cycle length, basal FSH levels, tubal status,history of previous pregnancies in the current relationship (ongoing pregnancies after natural conception, fertility treatment or miscarriages), semen volume, and semen morphology. Predictions from the revised model seem to concur better with observed pregnancy rates compared with the Hunault model; c-statistic of 0.71 (95% CI 0.69 to 0.73) compared with 0.59 (95% CI 0.57 to 0.61).

Realizing a desired family size: when should couples start?

STUDY QUESTION: Until what age can couples wait to start a family without compromising their chances of realizing the desired number of children? SUMMARY ANSWER: The latest female age at which a couple should start trying to become pregnant strongly depends on the importance attached to achieving a desired family size and on whether or not IVF is an acceptable option in case no natural pregnancy occurs. WHAT IS KNOWN ALREADY: It is well established that the treatment-independent and treatment-dependent chances of pregnancy decline with female age. However, research on the effect of age has focused on the chance of a first pregnancy and not on realizing more than one child. STUDY DESIGN, SIZE, DURATION: An established computer simulation model of fertility, updated with recent IVF success rates, was used to simulate a cohort of 10 000 couples in order to assess the chances of realizing a one-, two- or three-child family, for different female ages at which the couple starts trying to conceive. PARTICIPANTS/MATERIALS, SETTING, METHODS: The model uses treatment-independent pregnancy chances and pregnancy chances after IVF/ICSI. In order to focus the discussion, we single out three levels of importance that couples could attach to realizing a desired family size: (i) Very important (equated with aiming for at least a 90% success chance). (ii) Important but not at all costs (equated with a 75% success chance) (iii) Good to have children, but a life without children is also fine (equated with a 50% success chance). MAIN RESULTS AND THE ROLE OF CHANCE: In order to have a chance of at least 90% to realize a one-child family, couples should start trying to conceive when the female partner is 35 years of age or younger, in case IVF is an acceptable option. For two children, the latest starting age is 31 years, and for three children 28 years. Without IVF, couples should start no later than age 32 years for a one-child family, at 27 years for a two-child family, and at 23 years for three children. When couples accept 75% or lower chances of family completion, they can start 4-11 years later. The results appeared to be robust for plausible changes in model assumptions. LIMITATIONS, REASONS FOR CAUTION: Our conclusions would have been more persuasive if derived directly from large-scale prospective studies. An evidence-based simulation study (as we did) is the next best option. We recommend that the simulations should be updated every 5-10 years with new evidence because, owing to improvements in IVF technology, the assumptions on IVF success chances in particular run the risk of becoming outdated. WIDER IMPLICATIONS OF THE FINDINGS: Information on the chance of family completion at different starting ages is important for prospective parents in planning their family, for preconception counselling, for inclusion in educational courses in human biology, and for increasing public awareness on human reproductive possibilities and limitations. STUDY FUNDING/COMPETING INTERESTS: No external funding was either sought or obtained for this study. There are no conflicts of interest to be declared.

The influence of disease risk on the optimal time interval between screens for the early detection of cancer: a mathematical approach.

The intervals between screens for the early detection of diseases such as breast and colon cancer suggested by screening guidelines are typically based on the average population risk of disease. With the emergence of ever more biomarkers for cancer risk prediction and the development of personalized medicine, there is a need for risk-specific screening intervals. The interval between successive screens should be shorter with increasing cancer risk. A risk-dependent optimal interval is ideally derived from a cost-effectiveness analysis using a validated simulation model. However, this is time-consuming and costly. We propose a simplified mathematical approach for the exploratory analysis of the implications of risk level on optimal screening interval. We develop a mathematical model of the optimal screening interval for breast cancer screening. We verified the results by programming the simplified model in the MISCAN-Breast microsimulation model and comparing the results. We validated the results by comparing them with the results of a full, published MISCAN-Breast cost-effectiveness model for a number of different risk levels. The results of both the verification and validation were satisfactory. We conclude that the mathematical approach can indicate the impact of disease risk on the optimal screening interval.

Models in the development of clinical practice guidelines.

Clinical practice guidelines should be based on the best scientific evidence derived from systematic reviews of primary research. However, these studies often do not provide evidence needed by guideline development groups to evaluate the tradeoffs between benefits and harms. In this article, the authors identify 4 areas where models can bridge the gaps between published evidence and the information needed for guideline development applying new or updated information on disease risk, diagnostic test properties, and treatment efficacy; exploring a more complete array of alternative intervention strategies; assessing benefits and harms over a lifetime horizon; and projecting outcomes for the conditions for which the guideline is intended. The use of modeling as an approach to bridge these gaps (provided that the models are high-quality and adequately validated) is considered. Colorectal and breast cancer screening are used as examples to show the utility of models for these purposes. The authors propose that a modeling study is most useful when strong primary evidence is available to inform the model but critical gaps remain between the evidence and the questions that the guideline group must address. In these cases, model results have a place alongside the findings of systematic reviews to inform health care practice and policy.

Should colorectal cancer screening be considered in elderly persons without previous screening? A cost-effectiveness analysis.

BACKGROUND: The U.S. Preventive Services Task Force recommends against routine screening for colorectal cancer (CRC) in adequately screened persons older than 75 years but does not address the appropriateness of screening in elderly persons without previous screening. OBJECTIVE: To determine at what ages CRC screening should be considered in unscreened elderly persons and to determine which test is indicated at each age. DESIGN: Microsimulation modeling study. DATA SOURCES: Observational and experimental studies. TARGET POPULATION: Unscreened persons aged 76 to 90 years with no, moderate, and severe comorbid conditions. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTION: One-time colonoscopy, sigmoidoscopy, or fecal immunochemical test (FIT) screening. OUTCOME MEASURES: Quality-adjusted life-years gained, costs, and costs per quality-adjusted life-year gained. RESULTS OF BASE-CASE ANALYSIS: In unscreened elderly persons with no comorbid conditions, CRC screening was cost-effective up to age 86 years. Screening with colonoscopy was indicated up to age 83 years, sigmoidoscopy was indicated at age 84 years, and FIT was indicated at ages 85 and 86 years. In unscreened persons with moderate comorbid conditions, screening was cost-effective up to age 83 years (colonoscopy indicated up to age 80 years, sigmoidoscopy at age 81 years, and FIT at ages 82 and 83 years). In unscreened persons with severe comorbid conditions, screening was cost-effective up to age 80 years (colonoscopy indicated up to age 77 years, sigmoidoscopy at age 78 years, and FIT at ages 79 and 80 years). RESULTS OF SENSITIVITY ANALYSES: Results were most sensitive to assuming a lower willingness to pay per quality-adjusted life-year gained. LIMITATION: Only persons at average risk for CRC were considered. CONCLUSION: In unscreened elderly persons CRC screening should be considered well beyond age 75 years. A colonoscopy is indicated at most ages. PRIMARY FUNDING SOURCE: National Cancer Institute.

How distressing is referral to colposcopy in cervical cancer screening?: a prospective quality of life study.

OBJECTIVE: Referral for colposcopy because of abnormal Pap test results is likely to be distressing, but the extent and duration of these effects are unknown. We aimed to fill this gap. METHODS: We conducted a prospective observational study at two departments of Obstetrics and Gynecology (an academic and a non-academic setting). Women referred for colposcopy completed questionnaires before colposcopy, and at 1, 3, and 6 months afterwards. A reference group of 706 screen participants, aged 29-60 years old, was included and completed questionnaires once. Main outcome measures were generic health-related quality of life (HRQoL), assessed through the EQ-5D and the SF-12 physical and mental scores (PCS-12 and MCS-12); anxiety as assessed by STAI-6, and screen-specific anxiety as assessed by the psychological consequences questionnaire (PCQ). RESULTS: 154 women responded to the questionnaire, of whom 132 were included in the analyses. Histological results were CIN 1 in 17/115 women (15%) and CIN 2+ in 62 (54%). In 36 women (31%) there was no histologically confirmed neoplasia. Before colposcopy physical HRQoL scores were similar or slightly better than in the reference group, while mental HRQoL (MSC-12) and (screen-specific) anxiety were worse (p<0.001). Irrespective of CIN-grades, anxiety washed out during follow-up (p<0.001), with changes being clinically relevant. CONCLUSIONS: Referral for gynecological evaluation because of abnormal PAP-test results was distressing. Anxiety--and not the physical burden of management--seemed to be the most bothersome to women. For all CIN-grades, distress disappeared over six months following colposcopy, suggesting a reassuring effect of gynecological management.

Cost-effectiveness of one versus two sample faecal immunochemical testing for colorectal cancer screening.

OBJECTIVE: The sensitivity and specificity of a single faecal immunochemical test (FIT) are limited. The performance of FIT screening can be improved by increasing the screening frequency or by providing more than one sample in each screening round. This study aimed to evaluate if two-sample FIT screening is cost-effective compared with one-sample FIT. DESIGN: The MISCAN-colon microsimulation model was used to estimate costs and benefits of strategies with either one or two-sample FIT screening. The FIT cut-off level varied between 50 and 200 ng haemoglobin/ml, and the screening schedule was varied with respect to age range and interval. In addition, different definitions for positivity of the two-sample FIT were considered: at least one positive sample, two positive samples, or the mean of both samples being positive. RESULTS: Within an exemplary screening strategy, biennial FIT from the age of 55-75 years, one-sample FIT provided 76.0-97.0 life-years gained (LYG) per 1000 individuals, at a cost of € 259,000-264,000 (range reflects different FIT cut-off levels). Two-sample FIT screening with at least one sample being positive provided 7.3-12.4 additional LYG compared with one-sample FIT at an extra cost of € 50,000-59,000. However, when all screening intervals and age ranges were considered, intensifying screening with one-sample FIT provided equal or more LYG at lower costs compared with two-sample FIT. CONCLUSION: If attendance to screening does not differ between strategies it is recommended to increase the number of screening rounds with one-sample FIT screening, before considering increasing the number of FIT samples provided per screening round.

Random comparison of repeated faecal immunochemical testing at different intervals for population-based colorectal cancer screening.

OBJECTIVE: Colorectal cancer screening by means of faecal immunochemical tests (FITs) requires successive screening rounds for an optimal preventive effect. However, data on the influence of the length of the screening interval on participation and diagnostic yield are lacking. Repeated FIT screening was therefore performed in a population-based trial comparing various repeat intervals. DESIGN: 7501 Dutch individuals aged 50-74 years were randomly selected and invited for two 1-sample FIT screening rounds (haemoglobin (Hb) concentration ≥ 50 ng/ml, corresponding to 10 µg Hb/g faeces) with intervals of 1 (group I), 2 (group II) or 3 years (group III). RESULTS: In group I, participation was 64.7% in the first screening round and 63.2% in the second. The corresponding percentages for groups II and III were 61.0% vs 62.5% and 62.0% vs 64.0%. Triennial screening resulted in a higher participation rate in the second screening round compared with annual screening (p=0.04). The overall positivity rate in the second screening round was significantly lower compared with the first round (6.0% vs 8.4%; OR 0.69, 95% CI 0.58 to 0.82) and did not depend on interval length (p=0.23). Similarly, the overall detection rate of advanced neoplasia was significantly lower in the second round compared with the first screening round (1.9% vs 3.3%; OR 0.57, 95% CI 0.43 to 0.76) and also did not depend on interval length (p=0.62). The positive predictive value of the FIT did not significantly change over time (41% vs 33%; p=0.07). CONCLUSION: The total number of advanced neoplasia found at repeat FIT screening is not influenced by the interval length within a range of 1-3 years. Furthermore, there is a stable and acceptably high participation in the second screening round. This implies that screening intervals can be tailored to local resources.

Postpartum physical activity after preeclampsia.

OBJECTIVE: After mild and severe preeclampsia, to assess whether women meet the physical activity recommendation at 3 and 6months postpartum, and whether demographic, obstetric and anthropometric characteristics, mental health, and health-related quality of life are associated with less physical activity than recommended. STUDY DESIGN: Prospective cohort study. MAIN OUTCOME MEASURES: Self-reported physical activity in MET-min/week, percentage of women who fail to meet the physical activity recommendation. METHODS: Of the 255 women diagnosed with preeclampsia invited to participate in this prospective cohort study, 174 (68%) provided informed consent. Analyses were restricted to 141 participants who completed the short form of the International Physical Activity Questionnaire at 3 and/or 6months postpartum. Logistic regression analysis was used to evaluate changes in physical activity level over time, and to establish which variables were associated with failure to meet the postpartum physical activity recommendation. RESULTS: At both 3 and 6months postpartum, 38% of women failed to meet the physical activity recommendation. Failure was associated with severe preeclampsia, cesarean section, admission to the neonatal intensive care unit, low gestational age at delivery, and low birth weight (all p<0.05). CONCLUSIONS: There seems to be a need to stimulate physical activity in about one third of women after a pregnancy complicated by preeclampsia, particularly in case of severe preeclampsia and other adverse pregnancy outcomes. Tailored lifestyle interventions are needed for women who fail to meet the recommendation.

Fecal occult blood testing when colonoscopy capacity is limited.

BACKGROUND: Fecal occult blood testing (FOBT) can be adapted to a limited colonoscopy capacity by narrowing the age range or extending the screening interval, by using a more specific test or hemoglobin cutoff level for referral to colonoscopy, and by restricting surveillance colonoscopy. Which of these options is most clinically effective and cost-effective has yet to be established. METHODS: We used the validated MISCAN-Colon microsimulation model to estimate the number of colonoscopies, costs, and health effects of different screening strategies using guaiac FOBT or fecal immunochemical test (FIT) at various hemoglobin cutoff levels between 50 and 200 ng hemoglobin per mL, different surveillance strategies, and various age ranges. We optimized the allocation of a limited number of colonoscopies on the basis of incremental cost-effectiveness. RESULTS: When colonoscopy capacity was unlimited, the optimal screening strategy was to administer an annual FIT with a 50 ng/mL hemoglobin cutoff level in individuals aged 45-80 years and to offer colonoscopy surveillance to all individuals with adenomas. When colonoscopy capacity was decreasing, the optimal screening adaptation was to first increase the FIT hemoglobin cutoff value to 200 ng hemoglobin per mL and narrow the age range to 50-75 years, to restrict colonoscopy surveillance, and finally to further decrease the number of screening rounds. FIT screening was always more cost-effective compared with guaiac FOBT. Doubling colonoscopy capacity increased the benefits of FIT screening up to 100%. CONCLUSIONS: FIT should be used at higher hemoglobin cutoff levels when colonoscopy capacity is limited compared with unlimited and is more effective in terms of health outcomes and cost compared with guaiac FOBT at all colonoscopy capacity levels. Increasing the colonoscopy capacity substantially increases the health benefits of FIT screening.

The long-term effect of current and new interventions on the new case detection of leprosy: a modeling study.

BACKGROUND: Although the number of newly detected leprosy cases has decreased globally, a quarter of a million new cases are detected annually and eradication remains far away. Current options for leprosy prevention are contact tracing and BCG vaccination of infants. Future options may include chemoprophylaxis and early diagnosis of subclinical infections. This study compared the predicted trends in leprosy case detection of future intervention strategies. METHODS: Seven leprosy intervention scenarios were investigated with a microsimulation model (SIMCOLEP) to predict future leprosy trends. The baseline scenario consisted of passive case detection, multidrug therapy, contact tracing, and BCG vaccination of infants. The other six scenarios were modifications of the baseline, as follows: no contact tracing; with chemoprophylaxis; with early diagnosis of subclinical infections; replacement of the BCG vaccine with a new tuberculosis vaccine ineffective against Mycobacterium leprae ("no BCG"); no BCG with chemoprophylaxis; and no BCG with early diagnosis. FINDINGS: Without contact tracing, the model predicted an initial drop in the new case detection rate due to a delay in detecting clinical cases among contacts. Eventually, this scenario would lead to new case detection rates higher than the baseline program. Both chemoprophylaxis and early diagnosis would prevent new cases due to a reduction of the infectious period of subclinical cases by detection and cure of these cases. Also, replacing BCG would increase the new case detection rate of leprosy, but this effect could be offset with either chemoprophylaxis or early diagnosis. CONCLUSIONS: This study showed that the leprosy incidence would be reduced substantially by good BCG vaccine coverage and the combined strategies of contact tracing, early diagnosis, and treatment of infection and/or chemoprophylaxis among household contacts. To effectively interrupt the transmission of M. leprae, it is crucial to continue developing immuno- and chemoprophylaxis strategies and an effective test for diagnosing subclinical infections.

Attempting to explain heterogeneous HIV epidemics in sub-Saharan Africa: potential role of historical changes in risk behaviour and male circumcision.

BACKGROUND: A key conclusion of the Four Cities Study, carried out to explore reasons for heterogeneity in the HIV epidemic between two cities in sub-Saharan Africa with relatively low prevalence (Cotonou and Yaoundé) and two with high prevalence (Kisumu and Ndola), was that differences in biological cofactors outweighed differences in sexual risk behaviours. The authors explore an alternative hypothesis, that risk behaviours were historically higher in the high-prevalence cities. They also investigate the effects of different prevalence of male circumcision on the HIV epidemics in the four cities. METHODS: A transmission model was fitted to data from the Four Cities Study. Default scenarios included biological cofactor effects on HIV transmission. Counter-factual scenarios were simulated without biological cofactors, with and without higher historical sexual behaviours, and with various rates of male circumcision. RESULTS: Simulated adult HIV prevalence in 1997 for the default scenarios was 3.1%, 7.8%, 28.9% and 27.1% in Cotonou, Yaoundé, Kisumu and Ndola, respectively, in line with data. Without biological cofactors, even implausibly high historical levels of risk behaviour in East Africa could not reproduce the observed heterogeneity in the late 1990s. Increasing the proportion of men circumcised in Ndola from 10% to 100% reduced HIV prevalence in 1997 to 7%. Decreasing the proportion circumcised in Yaoundé from 100% to 10% increased HIV prevalence to 26%. CONCLUSIONS: Differences in male circumcision rates are likely to have played a key role in the heterogeneous spread of HIV across Africa. The effect of circumcision interventions can vary depending on the epidemic setting, with a larger effect in more generalised epidemics.

Postpartum depression after mild and severe preeclampsia.

OBJECTIVE: To describe the prevalence of postpartum depressive symptoms after preeclampsia, to assess the extent to which the prevalence of postpartum depressive symptoms differs after mild and severe preeclampsia, and to investigate which factors contribute to such differences. METHODS: Women diagnosed with preeclampsia (n=161) completed the Edinburgh Postnatal Depression Scale (EPDS) at 6, 12, or 26 weeks postpartum. Multiple logistic regression analysis was used to investigate the association between severity of preeclampsia, contributing factors and postpartum depression (PPD) (1) at any time during the first 26 weeks postpartum and (2) accounting for longitudinal observations at three time points. RESULTS: After mild preeclampsia, 23% reported postpartum depressive symptoms at any time up to 26 weeks postpartum compared to 44% after severe preeclampsia (unadjusted odds ratio [OR] 2.65, 95% confidence interval [CI] 1.16-6.05) for depression at any time up to 26 weeks postpartum (unadjusted OR 2.57, 95% CI, 1.14-5.76) while accounting for longitudinal observations. Admission to the neonatal intensive care unit (NICU) (adjusted OR 3.19, 95% CI 1.15-8.89) and perinatal death (adjusted OR 2.96, 95% CI 1.09-8.03) contributed to this difference. CONCLUSIONS: It appears that not the severity of preeclampsia itself but rather the consequences of the severity of the disease (especially admission to the NICU and perinatal death) cause postpartum depressive symptoms. Obstetricians should be aware of the high risk of postpartum depressive symptoms after severe preeclampsia, particularly among women whose infant has been admitted to the NICU or has died.

Symptoms of post-traumatic stress after preeclampsia.

This study describes the prevalence of postpartum post-traumatic stress disorder (PTSD) based on the DSM-IV criteria, including its symptoms of intrusion, avoidance and hyperarousal after pregnancies complicated by preeclampsia, and examines which variables are associated with PTSD and its symptoms. Women whose pregnancies were complicated by preeclampsia completed the Self-Rating Inventory for PTSD at 6 and 12 weeks postpartum: 149 women completed this questionnaire on at least one time point. Logistic regression analyses were used to examine associations with PTSD and its symptoms. Results showed that the prevalence of PTSD was 8.6% at 6 weeks, and 5.1% at 12 weeks postpartum; 21.9% of the study sample experienced postpartum symptoms of intrusion at 6 weeks postpartum (11.7% at 12 weeks), 9.4% symptoms of avoidance (8.0% at 12 weeks), and 28.9% symptoms of hyperarousal (20.4% at 12 weeks). Younger age, severe preeclampsia, cesarean section, lower gestational age, lower birth weight, admission to the neonatal intensive care unit, and perinatal death were found to be associated with PTSD and its symptoms. There was a relatively high prevalence of postpartum symptoms of PTSD among women after preeclampsia. The prevalence was highest among younger women who experienced more adverse pregnancy outcomes.

Cost-effectiveness analysis of a quantitative immunochemical test for colorectal cancer screening.

BACKGROUND & AIMS: Two European randomized trials (N = 30,000) compared guaiac fecal occult blood testing with quantitative fecal immunochemical testing (FIT) and showed better attendance rates and test characteristics for FIT. We aimed to identify the most cost-effective FIT cutoff level for referral to colonoscopy based on data from these trials and allowing for differences in screening ages. METHODS: We used the validated MIcrosimulation SCreening ANalysis (MISCAN)-Colon microsimulation model to estimate costs and effects of different screening strategies for FIT cutoff levels of 50, 75, 100, 150, and 200 ng/mL hemoglobin. For each cutoff level, screening strategies were assessed with various age ranges and screening intervals. We assumed sufficient colonoscopy capacity for all strategies. RESULTS: At all cost levels, FIT screening was most effective with the 50 ng/mL cutoff level. The incremental cost-effectiveness ratio of biennial screening between ages 55 and 75 years using FIT at 50 ng/mL, for example, was 3900 euro per life year gained. Annual screening had an incremental cost-effectiveness ratio of 14,900 euro per life year gained, in combination with a wider age range (between ages 45 and 80 years). In the sensitivity analysis, 50 ng/mL remained the preferred cutoff level. CONCLUSIONS: FIT screening is more cost-effective at a cutoff level of 50 ng/mL than at higher cutoff levels. This supports the recommendation to use FIT at a cutoff level of 50 ng/mL, which is considerably lower than the values used in current practice.

Practical implications of differential discounting in cost-effectiveness analyses with varying numbers of cohorts.

OBJECTIVE: To call attention to the influence of the number of birth-cohorts used in cost-effectiveness analysis (CEA) models on incremental cost-effectiveness ratios (ICERs) under differential discounting. METHODS: The consequences of increasing the number of birth-cohorts are demonstrated using a CEA of cervical cancer prevention as an example. The cost-effectiveness of vaccinating 12-year-old girls against the human papillomavirus is estimated with the MISCAN microsimulation screening analysis model for 1, 10, 20, and 30 birth-cohorts. Costs and health effects are discounted with equal rates of 4% and alternatively with differential rates of 4% and 1.5% respectively. The effects of increasing the number of cohorts are shown by comparing the ICERs under equal and differential discounting. RESULTS: The ICER decreases as the number of cohorts increases under differential discounting, but not under equal discounting. CONCLUSIONS: The variation of ICERs with the number of cohorts under differential discounting prompts questions regarding the appropriate specification of CEA models and interpretation of their results. In particular, it raises concerns that arbitrary variation in study specification leads to arbitrary variation in results. Such variations could lead to erroneous policy decisions. These findings are relevant to CEA guidance authorities, CEA practitioners, and decision makers. Our results do not imply a problem with differential discounting per se, yet they highlight the need for practical guidance for its use.

Clarifying differences in natural history between models of screening: the case of colorectal cancer.

BACKGROUND: Microsimulation models are important decision support tools for screening. However, their complexity makes them difficult to understand and limits realization of their full potential. Therefore, it is important to develop documentation that clarifies their structure and assumptions. The authors demonstrate this problem and explore a solution for natural history using 3 independently developed colorectal cancer screening models. METHODS: The authors first project effectiveness and cost-effectiveness of colonoscopy screening for the 3 models (CRC-SPIN, SimCRC, and MISCAN). Next, they provide a conventional presentation of each model, including information on structure and parameter values. Finally, they report the simulated reduction in clinical cancer incidence following a one-time complete removal of adenomas and preclinical cancers for each model. They call this new measure the maximum clinical incidence reduction (MCLIR). RESULTS: Projected effectiveness varies widely across models. For example, estimated mortality reduction for colonoscopy screening every 10 years from age 50 to 80 years, with surveillance in adenoma patients, ranges from 65% to 92%. Given only conventional information, it is difficult to explain these differences, largely because differences in structure make parameter values incomparable. In contrast, the MCLIR clearly shows the impact of model differences on the key feature of natural history, the dwell time of preclinical disease. Dwell times vary from 8 to 25 years across models and help explain differences in projected screening effectiveness. CONCLUSIONS: The authors propose a new measure, the MCLIR, which summarizes the implications for predicted screening effectiveness of differences in natural history assumptions. Including the MCLIR in the standard description of a screening model would improve the transparency of these models.