Opinions differ about the extent to which intervention research should and can directly assess the main patient-important health outcomes, what role surrogate endpoints can play, and which ...requirements should then apply to the scientific underpinning of clinical and policy decisions.
In a commentary we elaborate on this and provide guidance for dealing with related dilemmas.
Ethical, methodological and practical reasons for decision making based on surrogate endpoints can be that (1) reaching the intended patient-important health outcome would take too long to await direct RCT-based evidence, (2) experimental conditions have limited sustainability over time; and (3) the plausibility of an intervention's clinical efficacy, given the already available evidence regarding surrogate endpoints, goes beyond equipoise. Given an expected increase of interventions with a long term patient-important health outcome perspective, dealing with surrogate endpoints will remain an important challenge. Appropriately dealing with a surrogate endpoint includes (1) the assessment of its predictive value for the intended patient-important outcome, where GRADE guidelines for assessing ‘indirectness’ and ‘causal chain analysis’ can be helpful; (2) transparency of (absence of) evidence; (3) adequately updating the ‘knowledge mosaic’; (4) weighing different perspectives and values, and (5) monitoring whether adjustments need to be made. The remaining level of uncertainty must be balanced against the urgency of clinical or societal decision making and the disadvantages of postponing this. Criteria for using surrogate endpoints are suggested. Patients, citizens and policy makers can be involved in agreeing upon these criteria.
•To make clinical research results more relevant for individual patients, using qualitative types of generalization can have important added value.•We suggest several generalization types that can be ...used to individualize study results, using insights and methods from the social sciences.•If different types of generalization are combined, study results may become better applicable and therefore more relevant to individual patients.
The CaReQoL Asthma assesses the care-related quality of life outcomes of pulmonary rehabilitation retrospectively in patients with severe asthma. The questionnaire comprises five domains (physical ...functioning; social functioning; coping with asthma; knowledge about asthma; medication).
To investigate construct and criterion validity of the CaReQoL Asthma, as well as its responsiveness and minimal important change (MIC), in comparison with other health measures (AQLQ, ACQ and FEV
).
Eighty three adults with severe refractory asthma filled out the CaReQoL Asthma at 6 and 12 months after a 12-week personalized multidisciplinary pulmonary rehabilitation program in a tertiary asthma centre, either in Switzerland or The Netherlands. Construct validity and responsiveness were assessed by testing pre-defined hypotheses about associations with changes in AQLQ, ACQ and FEV
scores. Criterion validity and MIC was assessed using Global Perceived Effect (GPE). Factor analyses, Cronbach's alpha, Spearman's correlations, paired t-tests and Student-Newman-Keuls tests were performed.
Cronbach's alphas of the questionnaire domains ranged from 0.82 to 0.95. Good construct validity and responsiveness were found; 84% of the assessed correlations confirm pre-defined hypotheses and reflect both weak and moderate to strong correlations. Good criterion validity was also identified, with CaReQol scores discriminating better than other health measures between levels of GPE at 6 months post-rehabilitation. The MIC for the total score was estimated at 0.84.
These study results suggest that the CaReQoL Asthma is a valid and responsive instrument and shows to be a comprehensive and tailored questionnaire for evaluating and monitoring outcomes of pulmonary rehabilitation in patients with severe refractory asthma. In order to further substantiate the reliability and validity of the CaReQoL Asthma, as well as to monitor outcomes of pulmonary rehabilitation in patients with severe asthma, it is recommended to use the CaReQoL Asthma in addition to other disease specific instruments.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Uncomplicated Urinary Tract Infections (UTIs) are common in primary care resulting in substantial costs. Since antimicrobial resistance against antibiotics for UTIs is rising, accurate diagnosis is ...needed in settings with low rates of multidrug-resistant bacteria.
To compare the cost-effectiveness of different strategies to diagnose UTIs in women who contacted their general practitioner (GP) with painful and/or frequent micturition between 2006 and 2008 in and around Amsterdam, The Netherlands.
This is a model-based cost-effectiveness analysis using data from 196 women who underwent four tests: history, urine stick, sediment, dipslide, and the gold standard, a urine culture. Decision trees were constructed reflecting 15 diagnostic strategies comprising different parallel and sequential combinations of the four tests. Using the decision trees, for each strategy the costs and the proportion of women with a correct positive or negative diagnosis were estimated. Probabilistic sensitivity analysis was used to estimate uncertainty surrounding costs and effects. Uncertainty was presented using cost-effectiveness planes and acceptability curves.
Most sequential testing strategies resulted in higher proportions of correctly classified women and lower costs than parallel testing strategies. For different willingness to pay thresholds, the most cost-effective strategies were: 1) performing a dipstick after a positive history for thresholds below €10 per additional correctly classified patient, 2) performing both a history and dipstick for thresholds between €10 and €17 per additional correctly classified patient, 3) performing a dipstick if history was negative, followed by a sediment if the dipstick was negative for thresholds between €17 and €118 per additional correctly classified patient, 4) performing a dipstick if history was negative, followed by a dipslide if the dipstick was negative for thresholds above €118 per additional correctly classified patient.
Depending on decision makers' willingness to pay for one additional correctly classified woman, the strategy consisting of performing a history and dipstick simultaneously (ceiling ratios between €10 and €17) or performing a sediment if history and subsequent dipstick are negative (ceiling ratios between €17 and €118) are the most cost-effective strategies to diagnose a UTI.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Participants with a positive faecal immunochemical test (FIT) in screening programs for colorectal cancer (CRC) have a high risk for colorectal cancer and advanced adenomas. They are therefore ...recommended follow-up by colonoscopy. However, more than ten percent of positively screened persons do not adhere to this advice.
To investigate FIT-positive individuals' motives for non-adherence to colonoscopy advice in the Dutch CRC screening program.
Non-adherent FIT-positive participants of the Dutch CRC screening program.
We conducted semi structured in-depth interviews with 17 persons who did not undergo colonoscopy within 6 months after a positive FIT. Interviews were undertaken face-to-face and data were analysed thematically with open coding and constant comparison.
All participants had multifactorial motives for non-adherence. A preference for more personalised care was described with the following themes: aversion against the design of the screening program, expectations of personalised care, emotions associated with experiences of impersonal care and a desire for counselling where options other than colonoscopy could be discussed. Furthermore, intrinsic motives were: having a perception of low risk for CRC (described by all participants), aversion and fear of colonoscopy, distrust, reluctant attitude to the treatment of cancer and cancer fatalism. Extrinsic motives were: having other health issues or priorities, practical barriers, advice from a general practitioner (GP) and financial reasons.
Personalised screening counselling might have helped to improve the interviewees' experiences with the screening program as well as their knowledge on CRC and CRC screening. Future studies should explore whether personalised screening counselling also has potential to increase adherence rates.
Key points
Participants with a positive FIT in two-step colorectal cancer (CRC) screening programs are at high risk for colorectal cancer and advanced adenomas. Non-adherence after an unfavourable screening result happens in all CRC programs worldwide with the consequence that many of the participants do not undergo colonoscopy for the definitive assessment of the presence of colorectal cancer. Little qualitative research has been done to study the reasons why individuals participate in the first step of the screening but not in the second step. We found a preference for more personalised care, which was not reported in previous literature on this subject. Furthermore, intrinsic factors, such as a low risk perception and distrust, and extrinsic factors, such as the presence of other health issues and GP advice, may also play a role in non-adherence. A person-centred approach in the form of a screening counselling session may be beneficial for this group of CRC screening participants.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Abstract Purpose Whereas a diagnosis of acute uncomplicated urinary tract infection (UTI) in clinical practice comprises a battery of several diagnostic tests, these tests are often studied ...separately (in isolation from other test results). We wanted to determine the value of history and urine tests for diagnosis of uncomplicated UTIs, taking into account their mutual dependencies and information from preceding tests. Methods Women with painful and/or frequent micturition answered questions about their signs and symptoms (history) of UTIs and underwent urine tests. A culture was the reference standard (103 colony-forming units per milliliter). A diagnostic index was derived using logistic regression with bootstrapped backward selection and parameter-wise shrinkage. Risk thresholds for UTI of 30% and 70% were used to analyze discriminative properties. Six models were compared: (1) history only, (2) history + urine dipstick, (3) history + urine dipstick + urinary sediment, (4) history + urine dipstick + dipslide, and (5) history + urine dipstick + urinary sediment + dipslide; we then added (6) a test only for patients with an intermediate risk (between 30% and 70%) after the preceding test. Results One hundred ninety-six women were included (UTI prevalence 61%). Seven variables were selected from history (3), dipstick (2), sediment (1), and dipslide (1). History correctly classified 56% of patients as having a UTI risk of either <30% or >70%. History and urine dipstick raised this to 73%. The 3 models with the addition of urinary sediment and dipslide, separately and in combination, performed hardly better. The sixth model, in which those at intermediate risk after history and received an additional test, correctly classified 83%. The patient's suspicion of a UTI and a positive nitrite test were the strongest indicators of a UTI. Conclusions Most women with painful and/or frequent micturition can be correctly classified as having either a low or a high risk of UTI by asking 3 questions: Does the patient think she has a UTI? Is there at least considerable pain on micturition? Is there vaginal irritation? Other women require additional urine dipstick investigation. Sediment and dipslide have little added value. External validation of these recommendations is required before they are implemented in practice.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
We aimed to assess participant-reported factors associated with non-follow-up with colonoscopy in colorectal cancer (CRC) screening.
In May 2019, we distributed a nationwide cross-sectional ...questionnaire (n = 4,009) to participants in the Dutch CRC screening program who received a positive fecal immunochemical test (FIT). Among respondents who reported no colonoscopy, we assessed the presence of a contraindication, and those without were compared with those who reported colonoscopy by logistic regression analysis.
Of 2,225 respondents (56% response rate), 730 (33%) reported no colonoscopy. A contraindication was reported by 55% (n = 404). Decisional difficulties (odds ratio OR = 0.29; 95% CI, 0.18-0.47), lacking the opportunity to discuss the FIT outcome (OR = 0.45; 95% CI, 0.28-0.72), and a low estimated risk of CRC (OR = 0.45; 95% CI, 0.26-0.76) were negatively associated with follow-up. Knowledge items negatively associated with follow-up included having an alternative explanation for the positive FIT (OR = 0.3; 95% CI, 0.21-0.43), having trust in the ability to self-detect CRC (OR = 0.42; 95% CI, 0.27-0.65), and thinking that polyp removal is ineffective (OR = 0.59; 95% CI, 0.43-0.82). The belief that the family physician would support colonoscopy showed the strongest positive association with follow-up (OR = 2.84; 95% CI, 2.01-4.02) CONCLUSIONS: Because decisional difficulties and certain convictions regarding CRC and screening are associated with non-follow-up, personalized screening counseling might be an intervention worth exploring as a means of improving follow-up in the Dutch CRC screening program. Involving family physicians might also prove beneficial.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background
Colorectal cancer (CRC) is the second most diagnosed cancer in men and women and second most common cause of cancer death in Australia; Australia’s CRC incidence and mortality are among ...the world’s highest. The Australian National Bowel Cancer Screening Program began in 2006; however, only 33% of those approached for the first time by the Program between 2018 and 2019 returned the kit. Of the 5.7 million kits sent during this period, only 44% were returned. Our aim was to identify practices and features of national bowel cancer screening programs in countries with similar programs but higher screening participation, to identify potential interventions for optimising Australian CRC screening participation.
Methods
We searched published and grey literature for CRC screening programs reporting at least 50% screening participation using postal invitation and free return of iFOBT home kits. Interviews were conducted with cancer registry staff and academic researchers, focused on participant and practitioner engagement in screening.
Results
National programs in Netherlands, Scotland, Denmark, and Finland reported over 50% screening participation rates for all invitation rounds. Shared characteristics include small populations within small geographic areas relative to Australia; relatively high literacy; a one-sample iFOBT kit; national registration systems for population cancer screening research; and screening program research including randomised trials of program features.
Conclusions
Apart from the one-sample kit, we identified no single solution to persistent Australian low uptake of screening. Research including randomised trials within the program promises to increase participation.
Impact
This screening program comparison suggests that within-program intervention trials will lead to increased Australian screening participation.
There is increasing attention on machine learning (ML)-based clinical decision support systems (CDSS), but their added value and pitfalls are very rarely evaluated in clinical practice. We ...implemented a CDSS to aid general practitioners (GPs) in treating patients with urinary tract infections (UTIs), which are a significant health burden worldwide.
This study aims to prospectively assess the impact of this CDSS on treatment success and change in antibiotic prescription behavior of the physician. In doing so, we hope to identify drivers and obstacles that positively impact the quality of health care practice with ML.
The CDSS was developed by Pacmed, Nivel, and Leiden University Medical Center (LUMC). The CDSS presents the expected outcomes of treatments, using interpretable decision trees as ML classifiers. Treatment success was defined as a subsequent period of 28 days during which no new antibiotic treatment for UTI was needed. In this prospective observational study, 36 primary care practices used the software for 4 months. Furthermore, 29 control practices were identified using propensity score-matching. All analyses were performed using electronic health records from the Nivel Primary Care Database. Patients for whom the software was used were identified in the Nivel database by sequential matching using CDSS use data. We compared the proportion of successful treatments before and during the study within the treatment arm. The same analysis was performed for the control practices and the patient subgroup the software was definitely used for. All analyses, including that of physicians' prescription behavior, were statistically tested using 2-sided z tests with an α level of .05.
In the treatment practices, 4998 observations were included before and 3422 observations (of 2423 unique patients) were included during the implementation period. In the control practices, 5044 observations were included before and 3360 observations were included during the implementation period. The proportion of successful treatments increased significantly from 75% to 80% in treatment practices (z=5.47, P<.001). No significant difference was detected in control practices (76% before and 76% during the pilot, z=0.02; P=.98). Of the 2423 patients, we identified 734 (30.29%) in the CDSS use database in the Nivel database. For these patients, the proportion of successful treatments during the study was 83%-a statistically significant difference, with 75% of successful treatments before the study in the treatment practices (z=4.95; P<.001).
The introduction of the CDSS as an intervention in the 36 treatment practices was associated with a statistically significant improvement in treatment success. We excluded temporal effects and validated the results with the subgroup analysis in patients for whom we were certain that the software was used. This study shows important strengths and points of attention for the development and implementation of an ML-based CDSS in clinical practice.
ClinicalTrials.gov NCT04408976; https://clinicaltrials.gov/ct2/show/NCT04408976.
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