Background & Aims In the Active Ulcerative Colitis Trial (ACT)-1 and ACT-2, patients with ulcerative colitis treated with infliximab were more likely than those given placebo to have a clinical ...response, undergo remission, and have mucosal healing. We investigated the association between early improvement (based on endoscopy) and subsequent clinical outcome. Methods Patients underwent endoscopic evaluations at weeks 0, 8, 30, and 54 (ACT-1 only), and were categorized into 4 subgroups by week 8 (Mayo endoscopy subscore, 0–3). The association of week 8 endoscopy subscores, subsequent colectomy risk, symptoms and corticosteroid use outcomes were analyzed. Mucosal healing was defined as a Mayo endoscopy subscore of 0 (normal) or 1 (mild). Results Infliximab-treated patients with lower week 8 endoscopy subscores were less likely to progress to colectomy through 54 weeks of follow-up evaluation ( P = .0004). This trend was not observed among patients given placebo ( P = .47). Patients with lower endoscopy subscores achieved better symptomatic and corticosteroid use outcomes at weeks 30 and 54 ( P < .0001, infliximab; P < .01, placebo). Among patients who achieved clinical response at week 8, trends in subsequent clinical outcomes by week 8 endoscopy subscores were generally consistent with that for the overall patient population; no trends were observed among patients who achieved clinical remission. Conclusions The degree of mucosal healing after 8 weeks of infliximab was correlated with improved clinical outcomes including colectomy. Similar trends were observed for all outcomes except colectomy among the subgroup with clinical response at week 8. The degree of mucosal healing at week 8 among those in clinical remission did not predict subsequent disease course.
Objective. To study the influence of counseling on women's contraceptive decisions. Design. A cross‐sectional multicenter study. Setting. Seventy Swedish family planning clinics. Population. Women ...aged 15–40 years attending for a contraceptive consultation who expressed interest in a combined hormonal contraceptive (CHC) method. Methods. Structured counseling about three CHCs and questionnaires completed after counseling from the healthcare professional. Main Outcome Measures. Method originally requested, perceptions of CHC attributes, method chosen and reasons for the choice. Results. In all, 173 healthcare professionals and 1 944 women participated. The mean standard deviation (SD) age of the women was 22.6(6.1) years. After structured counseling, a majority of women (56.0%; n=1 069; 95% confidence interval (CI) 53.1–58.9) chose the daily pill, 6.2% (n=118; 95% CI 4.9–7.8) chose the weekly patch, and 22.5% (n=430; 95% CI 20.2–25.1) chose the monthly ring. The weekly patch was chosen more often after counseling (6.2 vs 2.4% before counseling; p<0.0001). The greatest change was in the proportion of women who chose the contraceptive ring after counseling (22.5% vs. 8.5% before counseling; p<0.0001). The proportion of undecided women after counseling was reduced considerably (3.9% vs. 27.8% before counseling). Among the 523 women who were undecided before counseling, 50.6% chose the pill, 10.2% the patch and 24.6% the ring, while 20.9% of women who initially requested the pill changed to another method. Conclusions. Structured counseling facilitated choice of contraceptive method for most women, leading to changes in women's selection of a CHC method.
In a survey involving 281 patients awaiting assisted reproduction treatment at five centres in three countries, and 289 population controls, we investigated whether the patients had experienced more ...negative emotional feelings and negative emotional impact during periods when they were attempting to conceive as compared with the controls, and whether there was any difference in their well-being at the time of consultation. The study was performed in the context of currently divergent views as to the burden of fertility problems. The survey was carried out using questionnaires of the self-administration type. Women with fertility problems did in fact consistently report a higher prevalence of negative emotions than the controls with reference to the periods during which they had been trying to conceive. Patients reported more changes in interpartner relationships (either negative or positive). Sexuality was negatively affected among the patients. At the time of consultation, the patients had less favourable scores than the controls on scales for depressed mood, memory/concentration, anxiety and fears, as well as for self-perceived attractiveness. One in four (24.9%) of the patients had scores indicating depressive disorders as compared with only 6.8% of the controls. Current well-being was even more markedly affected in patients with previous unsuccessful in-vitro fertilization (IVF) experience. The `infertility' life event was perceived as severe by both patients and controls. Both prior to consultation and during diagnosis and treatment, women with fertility problems had a higher prevalence of reported negative psycho-emotional experiences than women without fertility problems.
User satisfaction and the physical and psychological effects of five commonly used contraceptive methods were investigated in a population survey among 1466 West German women. The focus was on ...effects attributed by current and past users to these methods, rather than objectively assessed effects, to shed further light on personal experiences that are highly relevant to the user but often remain unknown to prescribers and unreported in the medical literature. Within the overall sample, 1303 women were surveyed concerning their current or past use of oral contraceptives (OC), 996 regarding condoms, 342 with respect to intrauterine devices (IUD), 428 in regard to natural family planning (NFP), and 139 in relation to sterilization (respondents completed questions about each method used). It emerged that satisfaction was greatest with sterilization (92% of users), followed by OC (68% of ever users), IUD (59%), NFP (43%), and condoms (30%). Almost one in three NFP users had experienced an unwanted pregnancy during use of this method, as compared with one in 20 OC and condom users. The majority of users reported no mood changes during use of the methods studied. The percentages reporting negative mood changes (various items were scored) were up to 16% among OC users, 23% among condom users, and 30% among NFP users. The latter observations suggested that subjective side effects of a contraceptive agent on mood generally reflected, at least in part, the user’s sense of confidence in the method concerned (notably, with regard to efficacy and safety). Oral contraceptives, IUD, and sterilization had a broadly positive impact on sex life, whereas that of condoms was often negative. Whereas OC users often reported less heavy and painful menstruation (in up to 56% of cases), IUD were associated with heavier, prolonged, and more painful menstruation (in up to 65% of cases), as also was sterilization, although to a lesser extent (in up to 32% of cases). Overall, the study findings indicated that OC and sterilization had less negative impact on physical and psychological functioning than the other methods studied, in contrast to what the general public often believes.
Objectives
To examine the validity and statistical limitations of exploratory analyses of clinical trial data commonly requested by agencies responsible for determining which medical products may be ...financed or reimbursed by a healthcare system.
Design
This was a retrospective review of efficacy and safety analyses conducted for German Health Technology Assessment (HTA) evaluations with a decision date between 2015 and 2020, and an illustrative safety-related exploratory analysis of data from two phase III clinical trials of verubecestat (an anti-amyloid drug whose development was stopped for lack of efficacy) as would be mandated by the German HTA agency.
Results
We identified 422 HTA evaluations of 404 randomised controlled clinical trials. For 140 trials (34.7%), the evaluation was based on subpopulations of participants in the originating confirmatory trial (175 subpopulations were assessed). In 57% (100 of 175), the subpopulation sample size was 50% or less of the original study population. Detailed analysis of five evaluations based on subpopulations of the original trial is presented. The safety-related exploratory analysis of verubecestat led to 206 statistical analyses for treatments and 812 treatment-by-subgroup interaction tests. Of 31 safety endpoints with an elevated HR (suggesting association with drug treatment), the HR for 81% of these (25 of 31) was not elevated in both trials. Of the 812 treatment-by-subgroup interactions evaluated, 26 had an elevated HR for a subgroup in one trial, but only 1 was elevated in both trials.
Conclusions
Many HTA evaluations rely on subpopulation analyses and numerous post hoc statistical hypothesis tests. Subpopulation analysis may lead to loss of statistical power and uncontrolled influences of random imbalances. Multiple testing may introduce spurious findings. Decisions about benefits of medical products should therefore not rely on exploratory analyses of clinical trial data but rather on prospective clinical studies and careful synthesis of all available evidence based on prespecified criteria.
The European CHOICE study was a cross-sectional survey that evaluated women's combined hormonal contraceptive choices before and after contraceptive counseling in Austria, Belgium, Czech Republic and ...Slovakia, the Netherlands, Poland, Sweden, Switzerland, Israel, Russia, and Ukraine. The changes in method selection before and after counseling were reported previously. In this paper we present the reasons given by the 18,787 participating women for selecting their contraceptive method of choice, as well as their perceptions about the contraceptive pill, patch, and ring after counseling.
Women with an interest in a combined hormonal contraceptive method (pill, patch, or ring) were counseled using a standardized counseling leaflet. The women completed questionnaires, which included questions on why they had selected a particular method of contraception, and the extent to which they agreed with statements about the attributes of the pill, patch, and ring. The results for each country were compared with the percentages for all countries combined by using a binomial regression model. Multiple logistic regression models were used to investigate the extent to which the probability of choosing a method was related to prespecified aspects (i.e. perceptions) of each contraceptive method.
'Easy to use', 'convenience', and 'regular menstrual bleeding' were important selection criteria. 'Nondaily administration' was one of the main reasons women selected the patch or ring. 'Daily use' and 'will forget to take it' were the primary reasons for not selecting the pill, while the main reasons for not choosing the patch included 'not discrete, visible' and 'can fall off'. In a small number of instances, the ring was rejected because some women don't like to use a 'foreign body'. Women's perceptions influenced their contraceptive decisions: positive perceptions about a method increased the likelihood that a woman would select it. After counseling, many women associated the pill with forgetfulness, and many still did not know about the patch or ring's key attributes. Women's knowledge about a particular method was generally greater if they had chosen it.
To support informed contraceptive decision-making, healthcare professionals should realize that a woman's view of a method's ease of use is more important than perceived efficacy, tolerability, health benefits, or risks.
ABSTRACT
Objectives To encourage healthcare professionals to counsel women seeking combined hormonal contraceptives (CHCs) about alternative CHCs and to study the influence of counselling on women's ...selection of CHCs.
Methods Women (15-40 years old) in 11 countries who consulted HCPs about CHCs were counselled about the pill, transdermal patch, and vaginal ring. Both the HCPs and the women completed questionnaires.
Results Of women who were counselled (n = 18,787), 47% selected another CHC method than originally planned. One in four who intended to use the pill chose another method (16% chose the patch; 65% chose the ring). In total, patch use increased from 5% -8% (difference = 3.7% 97.5% CI: 3.3-4.2; p < 0.0001). Ring use nearly quadrupled from 8% -30% (difference = 21.7% 97.5% CI: 21.0-22.5; p < 0.0001). Nearly all women who were undecided prior to counselling selected a method after counselling. Selection of the pill increased most in Russia (+ 11%) and Sweden (+ 5%); patch selection was greatest in Russia (+ 7%) and Israel (+ 6%); ring use increased most in Ukraine and in the Czech Republic and Slovakia (+ 36%).
Conclusions Counselling increases use of alternative CHCs, such as the patch and the ring. Considerable differences between countries were noted.
Abstract
Objectives To investigate which characteristics of women and healthcare professionals (HCPs) were associated with changing to another combined hormonal contraceptive (CHC) method after ...contraceptive counselling.
Methods CHOICE was a cross-sectional survey in which 18,787 women were counselled about combined hormonal contraceptives, during which their contraceptive methods preferred both prior to and after counselling were recorded. In this subanalysis, characteristics associated with changing the method after counselling were determined using logistic regression models.
Results The probability of intending to change from the pill to another method was associated with being older; university-educated; being in a steady relationship; a prior unintended pregnancy; a younger HCP or one who recommended methods other than the pill. Changing to the patch was associated with a female HCP or a HCP who recommended the patch or an injectable. Changing to the ring was associated with being over 21 years; university-educated; being in a relationship; previous hormonal method use; and counselling by a female HCP, a HCP < 60 years old, or a HCP who recommended the ring or an implant. The country of residence influenced these changes in a complex pattern.
Conclusions Women's choice of CHC methods after contraceptive counselling are influenced by their age, educational background, relationship status, prior unplanned pregnancies and country of residence, as well as age, gender and preferences of their HCP.
To identify factors associated with long-term hormone replacement therapy (HRT) and reasons for early discontinuation of it.
A cross-sectional study was conducted in four United Kingdom group general ...practices. Six hundred fifteen past or present HRT users (representing a response rate of 66%) responded to questionnaires on HRT and potential determinants of long-term use. Main outcome measures were long-term HRT use (at least 6 years) as opposed to short-term use (at most 2 years) and self-reported reasons for discontinuation. Odds ratios (ORs) of long-term use were adjusted for age and other variables, in the same groups, calculated by logistic regression and 95% confidence intervals (CIs).
Ovariectomy (OR 2.59, 95% CI 1.12, 5.97), hysterectomy (OR 2.28, 95% CI 1.37, 3.79), previous oral contraceptive use (OR 1.76, 95% CI 1. 03, 3.01), HRT prescription to prevent osteoporosis (OR 1.81, 95% CI 1.04, 3.13), opinion that HRT prevents health problems (OR 3.22, 95% CI 1.57, 6.63), opinion that HRT is associated with health risks (OR 0.23, 95% CI 0.08, 0.65), and opinion that HRT has cosmetic benefits (OR 2.52, 95% CI 1.45, 4.40) were statistically significantly associated with long-term HRT. Women surveyed most often reported side effects and weight gain (each about 30%) as reasons for discontinuation, followed by possible health risks and dislike of menstrual bleeding or hormones (each about 15%).
Ovariectomy, hysterectomy, and opinions about benefits and disadvantages of HRT were the most important determinants of long-term use, whereas women themselves mentioned side effects and weight gain most frequently as reasons for discontinuing it.
This study addresses attitudes towards changes in menstrual bleeding patterns caused by oral contraceptives (OC) or hormone replacement therapy (HRT) and preferred changes in bleeding pattern with ...and without use of OC or HRT in relation to reproductive age group. Data were collected by means of telephone interviews with 325 women in each of four age groups (15–19, 25–34, 45–49, and 52–57 years). In total, 80.5% of currently menstruating women preferred one or more changes in bleeding pattern such as less painful, shorter, or less heavy periods, or amenorrhea. The majority of the menstruating women in all age groups preferred to have a bleeding frequency of less than once a month or never, whether the bleeding was spontaneous or induced by OC. In the case of HRT, amenorrhea was most preferred. These findings with respect to preferred bleeding frequency and OC may have important implications for health care providers and for future contraception development.
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