Emotional reactions to infertility diagnosis: thematic and natural language processing analyses of the 1000 Dreams survey.

RESEARCH QUESTION: What are the emotional effects of infertility on patients, partners, or both, and how can qualitative thematic analyses and natural language processing (NLP) help evaluate textual data? DESIGN: A cross-sectional, multi-country survey conducted between March 2019 and May 2019. A total of 1944 patients, partners, or both, from nine countries responded to the open-ended question asking about their initial feelings related to an infertility diagnosis. A mixed-method approach that integrated NLP topic modelling and thematic analyses was used to analyse responses. Sentiment polarity was quantified for each response. Linear regression evaluated the association between patient characteristics and sentiment negativity. RESULTS: Common emotional reactions to infertility diagnoses were sadness, depression, stress, disappointment, anxiety, frustration, confusion and loss of self-confidence. NLP topic modelling found additional reactions, i.e. shared feelings with partners, recollections about causes of infertility and treatment experience. Responses to the open-ended question were brief (median: three words) with 71.8% conveying negative sentiments. Some respondent characteristics showed small but significant associations with sentiment negativity, i.e. country (Spain, China and France were more negative than the USA, P < 0.001, P < 0.003 and P < 0.009 respectively), treatment engagement (no treatment was more negative than one or more treatment, P = 0.027) and marital status (missing/other was more negative than divorced, P = 0.003). CONCLUSION: Infertility diagnoses create an emotional burden for patients and partners. The mixed-method approach provides a compelling synergy in support of the validity of these findings and shows potential for these techniques in future research.

Tailored support may reduce mental and relational impact of infertility on infertile patients and partners.

RESEARCH QUESTION: What is the psychological impact of infertility on infertile patients and partners of infertile patients? DESIGN: This online, international, quantitative survey assessed the impact of infertility on mental health, relationships and daily activities for 1944 respondents. Respondents were male or female infertile patients (n = 1037) or partners to infertile patients (n = 907; not necessarily partners of the patient sample) and were recruited at different stages of the treatment journey. RESULTS: The most common emotions were 'sadness' at infertility diagnosis and 'anxiety' during treatment. Emotions differed in nature and intensity throughout the journey. Envy of others who achieved pregnancy was frequently reported by women. More than half of respondents (60.4%; n = 1174) perceived the infertility journey to have impacted their mental health, and 44.1% (n = 857) of respondents sought mental health support. More patients reported mental health impacts (70.1%, n = 727) than partners (49.3%, n = 447). One in three respondents indicated that their relationship had suffered due to the infertility diagnosis. Of these respondents, 55.0% (n = 409) strongly agreed that infertility caused an emotional strain. Patients more often than partners reported a detrimental impact on daily activities. Respondents most commonly agreed with statements regarding an 'effect on work-life balance'. CONCLUSION: Treatment journey stages are defined by their impact profile, which differs between infertile patients and partners of infertile patients. Negative impacts are diverse (mental health, relational, daily activities). There was disparity between the number of respondents reporting mental health issues and the number seeking mental health support. This indicates the need for support services tailored to different treatment stages.

How Do People with Experience of Infertility Value Different Aspects of Assistive Reproductive Therapy? Results from a Multi-Country Discrete Choice Experiment.

OBJECTIVES: Assistive reproductive therapies can help those who have difficulty conceiving but different forms of assistive reproductive therapies are associated with different treatment characteristics. We undertook a large, multinational discrete choice experiment to understand patient preferences for assistive reproductive therapies. METHODS: We administered an online discrete choice experiment with persons who had experience with subfertility or assistive reproductive therapies in the USA, UK, the Nordic region (Denmark, Norway, Sweden, Finland), Spain, and China. Attributes encouraged trade-offs between effectiveness, risk of adverse effects, treatment (dis)comfort, (in)convenience, cost per cycle and shared decision making. We used multinomial logit and mixed-logit models to estimate preferences and attribute importance by country/region, and estimated willingness to pay for changes in attribute levels. RESULTS: A total of 7565 respondents participated. Mixed logit had a better fit than multinomial logit across all samples. Preferences moved in expected directions across all samples, but the relative importance of attributes differed between countries. Willingness to pay was greatest for improvements in effectiveness and a greater degree of shared decision making, and we observe a substantial 'option value' independent of treatment characteristics. Unexpectedly, preferences over cost were insignificant in the Chinese sample, limiting the use of willingness to pay in this sample. CONCLUSIONS: Respondents balanced concerns for effectiveness with other considerations, including the cost and (dis)comfort of treatment, and the degree of shared decision making, but there is also substantial option value independent of treatment characteristics, demonstrating value of assistive reproductive therapies to individuals with experience of subfertility. We hypothesise that price insensitivity in the Chinese sample may reflect a degree of social desirability bias.

Barriers and factors associated with significant delays to initial consultation and treatment for infertile patients and partners of infertile patients.

RESEARCH QUESTION: What are the key drivers and barriers for infertile patients and their partners to see an infertility specialist and initiate treatment? DESIGN: An online, international, 30-minute quantitative survey collected data from 1944 respondents from nine countries. Respondents were infertile patients (n = 1037) or partners of infertile patients (n = 907; but not necessarily partners of the patient sample), at different stages of the treatment journey. RESULTS: The overall average times were 3.2 years to receiving a medical infertility diagnosis, 2.0 years attempting to achieve pregnancy without assistance before treatment, and 1.6 years of treatment before successful respondents achieved pregnancy. The most common driver for considering treatment after a consultation (n = 1025) was an equal desire within the couple to have a child (40.8%). Of the partners (n = 356), 29.8% reported that transparency of information from healthcare professionals about treatment expectations was important. A significantly higher proportion of respondents seeking treatment reported that healthcare professionals offered supportive services (61.2%) and mental health services (62.0%), than of the 207 respondents who did not seek treatment (32.4% and 36.7%, respectively; P < 0.001). Perceived cost was the most commonly reported barrier for respondents not seeking a consultation (37.5% of n = 352) or treatment (42.0% of n = 207). Of the 95 respondents who discontinued treatment, 34.7% discontinued due to the financial impact. CONCLUSIONS: Respondents reported significant delays to seeking treatment, probably negatively impacting the chances of achieving pregnancy. Motivational coherence within couples was a key driver and cost of treatment was the main barrier. Reported supportive service offerings by healthcare professionals were significantly associated with continuation of the treatment journey.

Is the public supportive and willing to pay for a national assistive reproductive therapies programme? Results from a multicountry survey.

OBJECTIVES: To understand attitudes towards infertility and willingness to pay (WTP) towards a publicly funded national assistive reproductive therapies (ART) programme. DESIGN: Attitudes survey with dichotomous and open-ended WTP questions. SETTING: Online survey administered in the USA, UK, Norway, Sweden, Finland, Denmark and China. PARTICIPANTS: 7945 respondents, analysed by country. Nordic respondents were pooled into a regionally representative sample. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome measures were proportion of sample agreeing with different infertility-related and ART-related value statements and supporting a monthly contribution to fund a national ART programme, expressed in local currency. Secondary outcome measure was maximum WTP. RESULTS: Across the nationally representative samples, 75.5% of all respondents agreed with infertility as a medical condition and 82.3% and 83.7% with ART eligibility for anyone who has difficulty having a baby or a medical problem preventing them from having a baby, respectively. 56.4% of respondents supported a defined monthly contribution and 73.9% supported at least some additional contribution to fund a national ART programme. Overall, converting to euros, median maximum WTP was €3.00 and mean was €15.47 (95% CI 14.23 to 16.72) per month. Maximum WTP was highest in China and the USA and lowest in the European samples. CONCLUSIONS: This large, multicountry survey extends our understanding of public attitudes towards infertility and fertility treatment beyond Europe. It finds evidence that a majority of the public in all sampled countries/regions views infertility as a treatable medical condition and supports the idea that all infertile individuals should have access to treatments that improve the chance of conception. There was also strong agreement with the idea that the desire for children is a basic human need. WTP questions showed that a majority of respondents supported a monthly contribution to fund a national ART programme, although there is some evidence of an acquiescence bias that may overstate support among specific samples.

Network meta-analyses for EGFR mutation-positive non-small-cell lung cancer: systematic review and overview of methods and shortcomings.

Aim: To perform a review of network meta-analyses (NMAs) for the first-line treatment of EGFR mutation-positive non-small-cell lung cancer, and to provide an overview of methodological approaches and potential shortcomings. Materials & methods: We conducted a systematic review of NMAs and evaluated their methodologies, including inclusion/exclusion criteria, information sources, results and outcomes, and statistical methodologies. Results: We identified ten published NMAs using five archetypical network structures. Despite similar objectives, there was substantial variability in the number of trials included in each NMA and in the relative treatment efficacy of the tyrosine kinase inhibitors. Conclusion: We identified methodological issues to explain differences in the findings, criteria for inclusion in NMAs and the degree of lumping of treatments. These factors should be given particular consideration in future research.

Budget impact of sequential treatment with first-line afatinib versus first-line osimertinib in non-small-cell lung cancer patients with common EGFR mutations.

BACKGROUND: The therapeutic landscape for non-small-cell lung cancer (NSCLC) patients that have common epidermal growth factor receptor (EGFR) mutations has changed radically in the last decade. The availability of these treatment options has an economic impact, therefore a budget impact analysis was performed. METHODS: A budget impact analysis was conducted from a Dutch healthcare perspective over a 5-year time horizon in EGFR-mutant NSCLC patients receiving first-line afatinib (Gilotrif®) versus first-line osimertinib (Tagrisso®), followed by subsequent treatments. A decision analysis model was constructed in Excel. Scenario analyses and one-way sensitivity analysis were used to test the models' robustness. RESULTS: Sequential treatment with afatinib versus first-line treatment with osimertinib showed mean total time on treatment (ToT) of 29.1 months versus 24.7 months, quality-adjusted life months (QALMs) of 20.2 versus 17.4 with mean cost of €108,166 per patient versus €143,251 per patient, respectively. The 5-year total budget impact was €110.4 million for the afatinib sequence versus €158.6 million for the osimertinib sequence, leading to total incremental cost savings of €48.15 million. CONCLUSIONS: First-line afatinib treatment in patients with EGFR-mutant NSCLC had a lower financial impact on the Dutch healthcare budget with a higher mean ToT and QALM compared to osimertinib sequential treatment.

Healthcare resource utilization and costs associated with patients prescribed afatinib or erlotinib as first-line therapy for EGFR mutation-positive NSCLC in the United States.

Aims: To assess healthcare resource utilization (HCRU) and costs in patients with non-small cell lung cancer treated with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors afatinib or erlotinib as first-line treatment.Materials and methods: This retrospective analysis used data from three large administrative claims databases in the US: Truven MarketScan, IMS PharMetrics Plus, and Optum Clinformatics Data Mart. Patients with diagnosis codes of lung cancer treated with afatinib or erlotinib were included in the sample. Treatment cohorts were matched on baseline characteristics using propensity scores to account for potential selection bias. HCRU and healthcare costs were compared between the matched afatinib and erlotinib cohorts.Results: In total, 3,152 patients met the study inclusion criteria; propensity score matching of the afatinib and erlotinib patients yielded 525 matched pairs with well-balanced baseline characteristics. The afatinib cohort had significantly fewer patients with ≥1 inpatient visits (40.4% vs 52.2%, p = 0.0001) and outpatient emergency room (ER) visits (45.7% vs 54.1%, p = 0.0066). Per patient per month (PPPM) visits were significantly different between afatinib compared to erlotinib for inpatient visits (0.1 vs 0.2, p = 0.0152), other outpatient visits PPPM (2.6 vs 3.0, p = 0.022) and outpatient office visits (2.0 vs 1.7, p = 0.0059). Although costs of outpatient office ($1,624 vs $1,070; p = 0.0086) and pharmacy ($6,709 vs $5,932; p < 0.0001) visits were higher for afatinib vs erlotinib, total costs did not differ significantly between cohorts ($14,972 vs $14,412; p = 0.4415).Limitations: Retrospective claims data can be subject to coding errors or data omissions; patients were required to have continuous health plan enrolment; EGFR mutation status was not confirmed.Conclusions: Patients treated with afatinib as first-line monotherapy experienced fewer inpatient stays and ER visits compared with erlotinib. Total costs were not significantly different between the two treatment cohorts.

First-line afatinib for advanced EGFRm+ NSCLC: Analysis of long-term responders in the LUX-Lung 3, 6, and 7 trials.

OBJECTIVES: In patients with advanced epidermal growth factor receptor mutation-positive (EGFRm+) non-small cell lung cancer (NSCLC), first-line afatinib significantly improved progression-free survival (PFS) and objective response vs. platinum-doublet chemotherapy in the phase III LUX-Lung 3 and LUX-Lung 6 trials, and significantly improved PFS, time to treatment failure and objective response vs. gefitinib in the phase IIb LUX-Lung 7 trial. We report post-hoc analyses of efficacy, safety and patient-reported outcomes (PROs) in afatinib long-term responders (LTRs) in these trials. METHODS: Treatment-naïve patients with stage IIIB/IV EGFRm + NSCLC randomized to afatinib in LUX-Lung 3/LUX-Lung 6/LUX-Lung 7 were included in the analysis. Patients treated with afatinib for ≥ 3 years were defined as LTRs. RESULTS: In LUX-Lung 3, LUX-Lung 6, and LUX-Lung 7, 24/229 (10%), 23/239 (10%) and 19/160 (12%) afatinib-treated patients were LTRs. Baseline characteristics were similar to the study populations, except for the proportions of women (LUX-Lung 3/LUX-Lung 6 only; 92/78% vs. 64% overall) and Del19-positive patients (63-79% vs. 49-58% overall). Median treatment duration among LTRs was 50, 56 and 42 months, and median PFS was 49.5, 55.5, and 42.2 months in LUX-Lung 3/LUX-Lung 6/LUX-Lung 7, respectively. Median overall survival could not be estimated. Frequency of afatinib dose reduction was consistent with the LUX-Lung 3/LUX-Lung 6/LUX-Lung 7 overall populations. PROs were stable in LTRs, with slight improvements after 3 years of afatinib treatment vs. baseline scores. CONCLUSIONS: In the LUX-Lung 3/LUX-Lung 6/LUX-Lung 7 trials, 10-12% of afatinib-treated patients were LTRs. Long-term afatinib treatment was independent of tolerability-guided dose adjustment and had no detrimental impact on safety or PROs.

Duration of treatment among patients prescribed afatinib or erlotinib as first-line therapy for EGFR mutation-positive non-small-cell lung cancer in the USA.

Aim: Evaluate duration of therapy among patients treated with afatinib or erlotinib as first-line therapy for non-small-cell lung cancer (NSCLC). Materials & methods: NSCLC patients initiating afatinib or erlotinib between 2014 and 2017 were identified in three large claims databases in the USA. Propensity score matching was conducted to compare the duration of treatment between patients by treatment. Results: Patients prescribed afatinib had a significantly longer median duration of treatment compared with those prescribed erlotinib (12.1 vs 9.9 months; p = 0.035) and experienced a 14% reduction in risk of discontinuing therapy (adjusted hazard ratio: 0.86; CI: 0.75-0.99). Conclusion: First-line treatment duration in a real-world setting was significantly longer for patients prescribed afatinib compared with erlotinib.

Influenced from the start: anchoring bias in time trade-off valuations.

PURPOSE: The de facto standard method for valuing EQ-5D health states is the time trade-off (TTO), an iterative choice procedure. The TTO requires a starting point (SP), an initial offer of time in full health which is compared to a fixed offer of time in impaired health. From the SP, the time in full health is manipulated until preferential indifference. The SP is arbitrary, but may influence respondents, an effect known as anchoring bias. The aim of the study was to explore the potential anchoring effect and its magnitude in TTO experiments. METHODS: A total of 1249 respondents valued 8 EQ-5D health states in a Web study. We used the lead time TTO (LT-TTO) which allows eliciting negative and positive values with a uniform method. Respondents were randomized to 11 different SPs. Anchoring bias was assessed using OLS regression with SP as the independent variable. In a secondary experiment, we compared two different SPs in the UK EQ-5D valuation study TTO protocol. RESULTS: A 1-year increase in the SP, corresponding to an increase in TTO value of 0.1, resulted in 0.02 higher recorded LT-TTO value. SP had little impact on the relative distance and ordering of the eight health states. Results were similar to the secondary experiment. CONCLUSION: The anchoring effect may bias TTO values. In this Web-based valuation study, the observed anchoring effect was substantial. Further studies are needed to determine whether the effect is present in face-to-face experiments.