On clinical trial fragility due to patients lost to follow up
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ABSTRACT: Background
Clinical trials routinely have patients lost to follow up. We propose a methodology to understand their possible effect on the results of statistical tests by altering the concept of the fragility index to treat the outcomes of observed patients as fixed but incorporate the potential outcomes of patients lost to follow up as random and subject to modification. Methods
We reanalyse the statistical results of three clinical trials on coronary artery bypass grafting (CABG) to study the possible effect of patients lost to follow up on the treatment effect statistical significance. To do so, we introduce the LTFU-aware fragility indices as a measure of the robustness of a clinical trial’s statistical results with respect to patients lost to follow up. Results
The analyses illustrate that clinical trials can either be completely robust to the outcomes of patients lost to follow up, extremely sensitive to the outcomes of patients lost to follow up, or in an intermediate state. When a clinical trial is in an intermediate state, the LTFU-aware fragility indices provide an interpretable measure to quantify the degree of fragility or robustness. Conclusions
The LTFU-aware fragility indices allow researchers to rigorously explore the outcomes of patients who are lost to follow up, when their data is the appropriate kind. The LTFU-aware fragility indices are sensitivity measures in a way that the original fragility index is not. Supplementary Information
The online version contains supplementary material available at (10.1186/s12874-021-01446-z).
SUBMITTER: Baer B
PROVIDER: S-EPMC8606097 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Long-term outcome studies are frequently hindered by a decreasing frequency of patient follow-up with the treating surgeon over time. Whether this attrition represents a "loss of faith" in their index surgeon or the realities of a geographically mobile society has never been assessed in a population of patients undergoing spinal surgery. The purpose of this article is to determine the frequency with which patients who have undergone prior surgery and develop new problems attempt to follow-up with their index spine surgeon. The study design was a population survey. All patients seen at two university-based spine centers over a 3-month period were surveyed regarding prior spine surgery. The questionnaire asked details of the previous operation, whether the patient had sought follow-up with their index surgeon, why the patient did not continue treatment with that surgeon, and whether the patient was satisfied with their prior treatment. Sixty-nine patients completed the survey. Prior operations were lumbar (53 patients) and cervical (16). When asked the reason for not seeing their prior surgeon, 10 patients (15%) stated that they (the patient) had moved and 16 (23%) responded that their surgeon no longer practiced in the area. Thirteen (19%) were unhappy with their previous care, 22 (32%) were seeking a second opinion, and 7 (10%) were told they needed more complex surgery. Thirty-seven (54%) discussed their symptoms with their original surgeon before seeking another surgeon. Although 32 patients (46%) had not discussed their new complaints with their index surgeon, only 3 patients (4%) chose not to return to their prior surgeon despite having the opportunity to do so. Forty-nine patients (71%) were satisfied with their prior surgical care, and 42 patients (61%) would undergo the index operation again. Most of the patients seen at the authors' practices after undergoing prior spine surgery elsewhere failed to follow up with their prior spine surgeon for geographical reasons. It appears that the majority of patients who develop new spinal complaints will seek out their treating surgeon when possible. This suggests that patient attrition over long-term follow-up may reflect a geographically mobile population rather than patient dissatisfaction with prior treatment.
| S-EPMC3854586 | biostudies-other
Project description:After bariatric surgery lifelong follow-up is recommended. Evidence of the consequences and reasons for being lost to follow-up (LTFU) is sparse. In this prospective study follow-up data of all patients who underwent bariatric surgery between 2008 and 2017 at a certified obesity centre were investigated. LTFU patients were evaluated through a structured telephone interview. Overall, 573 patients (female/male 70.9%/29.1%), aged 44.1 ± 11.2 years, preoperative BMI 52.1 ± 8.4 kg/m2 underwent bariatric surgery. Out of these, 33.2% had type 2 diabetes mellitus and 74.4% had arterial hypertension. A total of 290 patients were LTFU, of those 82.1% could be reached. Baseline characteristics of patients in follow-up (IFU) and LTFU were comparable, but men were more often LTFU (p = 0.01). Reported postoperative total weight loss (%TWL) and improvements of comorbidities were comparable, but %TWL was higher in patients remaining in follow-up for at least 2 years (p = 0.013). Travel issues were mentioned as the main reason for being LTFU. A percentage of 77.6% of patients reported to regularly supplement micronutrients, while 71.0% stated regular monitoring of their micronutrient status, mostly by primary care physicians. Despite comparable reported outcomes of LTFU to IFU patients, the duration of the in-centre follow-up period affected %TWL. There is a lack of sufficient supplementation and monitoring of micronutrients in a considerable number of LTFU patients.
| S-EPMC11357598 | biostudies-literature
Project description:ObjectiveThe retention of patients on antiretroviral therapy (ART) is key to achieving global targets in response to the HIV epidemic. Loss to follow-up (LTFU) can be substantial, with unknown outcomes for patients lost to ART programmes. We examined changes in outcomes of patients LTFU over calendar time, assessed associations with other study and programme characteristics and investigated the relative success of different tracing methods.MethodsWe performed a systematic review and logistic random-effects meta-regression analysis of studies that traced adults or children who started ART and were LTFU in sub-Saharan African treatment programmes. The primary outcome was mortality, and secondary outcomes were undocumented transfer to another programme, treatment interruption and the success of tracing attempts.ResultsWe included 32 eligible studies from 12 countries in sub-Saharan Africa: 20 365 patients LTFU were traced, and 15 708 patients (77.1%) were found. Compared to telephone calls, tracing that included home visits increased the probability of success: the adjusted odds ratio (aOR) was 9.35 (95% confidence interval [CI] 1.85-47.31). The risk of death declined over calendar time (aOR per 1-year increase 0.86, 95% CI 0.78-0.95), whereas undocumented transfers (aOR 1.13, 95% CI 0.96-1.34) and treatment interruptions (aOR 1.31, 95% CI 1.18-1.45) tended to increase. Mortality was lower in urban than in rural areas (aOR 0.59, 95% CI 0.36-0.98), but there was no difference in mortality between adults and children. The CD4 cell count at the start of ART increased over time.ConclusionsMortality among HIV-positive patients who started ART in sub-Saharan Africa, were lost to programmes and were successfully traced has declined substantially during the scale-up of ART, probably driven by less severe immunodeficiency at the start of therapy.
| S-EPMC5580236 | biostudies-literature
Project description:ObjectiveTo identify risk factors for failure to attend postpartum follow-up within 3 months of delivery, including social support, intrinsic motivation, insurance type and prenatal care attendance.Study designThis planned secondary analysis is derived from a randomized controlled trial of patients intending intrauterine device (IUD) use following their delivery (n=197). Subjects were postpartum from a vaginal or cesarean birth at ≥32 weeks' gestation. We obtained baseline demographics and certainty about their plan to receive a postpartum IUD. We administered validated scales for social support and intrinsic motivation at enrollment. We then reviewed health records for prenatal visits and any postpartum visit by 3 months and performed logistic regression to assess for predictors of follow-up.ResultsA total of 38/197 subjects (19.3%) failed to attend any postpartum visit by 3 months. Subjects who failed to follow up were more likely to have Medicaid versus private insurance (92% versus 8%, p<.01). Income <$50,000, no car, younger age, unplanned pregnancy, unemployment, multiple children, missed prenatal visits and late initiation of prenatal care were also associated with failure to follow up. Higher scores for social support and goal-directed motivation were not significantly associated with follow-up.ConclusionsIn our cohort, we found that one in five participants did not attend a postpartum visit by 3 months. Several socioeconomic indicators are associated with loss to follow-up, most notably Medicaid insurance. Having high motivation and social support is not sufficient to predict successful follow-up.ImplicationsThe main predictors for not attending a postpartum visit are Medicaid insurance or limited prenatal care, and not social support or intrinsic motivation. Interventions to improve postpartum contraception uptake should focus efforts on provision of immediate postpartum contraception for this population.
| S-EPMC6129217 | biostudies-literature
Project description:BackgroundLoss to follow-up (LTFU) is an unsuccessful treatment outcome for tuberculosis (TB) patients. In Malaysia, LTFU affects around 1 in 20 TB patients. Integration of qualitative research methods and evidence will provide a better understanding of LTFU and its underlying issues. In this study, we qualitatively explored TB patients' experiences in receiving treatment and their reasons for leaving TB care.MethodIn-depth interviews of 15 patients with a history of LTFU were conducted from January to September 2020. Interview guides were developed to explore TB patients' experiences while receiving treatment, including challenges faced and reasons for treatment interruption. Data were thematically analysed using the framework method.ResultsWe identified 11 emerging themes that occurred at four levels of interaction with TB patients. First, at the patient personal level, TB beliefs referring to patients' perception of illness and wellness, patients' perceived role of traditional and complementary medicine, and substance abuse were important. Second, the healthcare system and treatment factors that were highlighted included the organisation of care and treatment, interaction with healthcare professionals, particularly in communication and counselling, and TB medications' side effects. Third, structural factors including financial burden, logistical and transportation issues and work-related factors were identified to be barriers to treatment continuation. Fourth, the interpersonal level interaction of patients should not be neglected; this includes family relationships and support as well as peer influence.ConclusionStudy findings put forth issues and challenges faced by TB patients while receiving treatment and underscore areas where actions can be taken. This will contribute to informing the development and implementation of future TB control strategies that are responsive to TB patients' needs and concerns, to effectively address LTFU and ensure better treatment completion rates among TB patients in Malaysia.
| S-EPMC10484432 | biostudies-literature
Project description:Sarcoidosis + Follow-up 6 month after Keywords = sarcoidosis Keywords = follow-up Keywords: other
2005-01-18 | GSE1907 | GEO
Project description:BackgroundIncomplete ascertainment of outcomes in randomized controlled trials (RCTs) is likely to bias final study results if reasons for unavailability of patient data are associated with the outcome of interest. The primary objective of this study is to assess the potential impact of loss to follow-up on the estimates of treatment effect. The secondary objectives are to describe, for published RCTs, (1) the reporting of loss to follow-up information, (2) the analytic methods used for handling loss to follow-up information, and (3) the extent of reported loss to follow-up.MethodsWe will conduct a systematic review of reports of RCTs recently published in five top general medical journals. Eligible RCTs will demonstrate statistically significant effect estimates with respect to primary outcomes that are patient-important and expressed as binary data. Teams of 2 reviewers will independently determine eligibility and extract relevant information from each eligible trial using standardized, pre-piloted forms. To assess the potential impact of loss to follow-up on the estimates of treatment effect we will, for varying assumptions about the outcomes of participants lost to follow-up (LTFU), calculate (1) the percentage of RCTs that lose statistical significance and (2) the mean change in effect estimate across RCTs. The different assumptions we will test are the following: (1) none of the LTFU participants had the event; (2) all LTFU participants had the event; (3) all LTFU participants in the treatment group had the event; none of those in the control group had it (worst case scenario); (4) the event incidence among LTFU participants (relative to observed participants) increased, with a higher relative increase in the intervention group; and (5) the event incidence among LTFU participants (relative to observed participants) increased in the intervention group and decreased in the control group.DiscussionWe aim to make our objectives and methods transparent. The results of this study may have important implications for both clinical trialists and users of the medical literature.
| S-EPMC2706244 | biostudies-literature
Project description:BackgroundLost to follow-up (LTF) represents an understudied barrier to effective management of chronic subdural hematoma (cSDH). Understanding the factors associated with LTF after surgical treatment of cSDH could uncover pathways for quality improvement efforts and modify discharge planning. We sought to identify the demographic and clinical factors associated with patient LTF.MethodsA single-institution, retrospective cohort study of patients treated surgically for convexity cSDH from 2009 to 2019 was conducted. The primary outcome was LTF, with neurosurgical readmission as the secondary outcome. Univariate analysis was conducted using the student-t test and χ2 test. Multivariate logistic regression was performed to identify the factors associated with LTF and neurosurgical readmission.ResultsA total of 139 patients were included, 29% of whom were LTF. The mean first postoperative follow-up duration was 60 days. On univariate analysis, uninsured/Medicaid coverage was associated with increased LTF compared with private insurance/Medicare coverage (62.5% vs. 41.4%; P = 0.039). A higher discharge modified Rankin scale score was also associated with LTF (3.7 vs. 3.5; P < 0.001). On multivariate analysis, uninsured/Medicaid patients had a significantly greater risk of LTF compared with private insurance/Medicare patients (odds ratio, 2.44; 95% confidence interval, 1.13-5.23; P = 0.022). LTF was independently associated with an increased risk of neurosurgical readmission (odds ratio, 1.94; 95% confidence interval, 1.17-3.24; P = 0.011).ConclusionsUninsured and Medicaid patients had a greater likelihood of LTF compared with private insurance and Medicare patients. LTF was further associated with an increased risk of neurosurgical readmission. The results from the present study emphasize the need to address barriers to follow-up to reduce readmission after surgery for cSDH. These findings could inform improved discharge planning, such as predischarge repeat imaging studies and postdischarge contact.
| S-EPMC8054037 | biostudies-literature
Project description:Background:Phosphomannomutase 2 deficiency (PMM2-CDG) is the most common congenital disorder of glycosylation (CDG). Hypoglycemia has been reported in various CDG including PMM2-CDG. The frequency and etiology of hypoglycemia in PMM2-CDG are not well studied. Methods:We conducted a systematic review of the literature on genetically and/or biochemically confirmed PMM2-CDG patients who developed hypoglycemia. Prospective follow-up information on the patients who received diazoxide therapy was collected and evaluated. Results:A total of 165 peer-reviewed articles reporting on 933 PMM2-CDG patients were assessed. Hypoglycemia was specifically mentioned only in 23 of these patients (2.5%). Hyperinsulinism was identified in 10 patients (43% of all hypoglycemic patients). Among these 10 patients, seven were successfully treated with diazoxide. However, most patients remained on therapy longer than a year to stay free of hypoglycemia. Conclusion:Hypoglycemia is a rarely reported finding in patients with PMM2-CDG. Diazoxide-responsive hyperinsulinism was found to have a good prognosis on medication in our PMM2-CDG patients with hypoglycemia. No genotype-phenotype correlation was observed with respect to hyperinsulinism. A prospective study should be undertaken to explore the hypothesis that hypoglycemia is underdiagnosed in PMM2-CDG and to evaluate whether hyperinsulinism is always associated with hypoglycemia.
| S-EPMC7012739 | biostudies-literature
Project description:IntroductionVaginismus is mostly unknown among clinicians and women. Vaginismus causes women to have fear, anxiety, and pain with penetration attempts.AimTo present a large cohort of patients based on prior published studies approved by an institutional review board and the Food and Drug Administration using a comprehensive multimodal vaginismus treatment program to treat the physical and psychologic manifestations of women with vaginismus and to record successes, failures, and untoward effects of this treatment approach.MethodsAssessment of vaginismus included a comprehensive pretreatment questionnaire, the Female Sexual Function Index (FSFI), and consultation. All patients signed a detailed informed consent. Treatment consisted of a multimodal approach including intravaginal injections of onabotulinumtoxinA (Botox) and bupivacaine, progressive dilation under conscious sedation, indwelling dilator, follow-up and support with office visits, phone calls, e-mails, dilation logs, and FSFI reports.Main outcome measuresLogs noting dilation progression, pain and anxiety scores, time to achieve intercourse, setbacks, and untoward effects. Post-treatment FSFI scores were compared with preprocedure scores.ResultsOne hundred seventy-one patients (71%) reported having pain-free intercourse at a mean of 5.1 weeks (median = 2.5). Six patients (2.5%) were unable to achieve intercourse within a 1-year period after treatment and 64 patients (26.6%) were lost to follow-up. The change in the overall FSFI score measured at baseline, 3 months, 6 months, and 1 year was statistically significant at the 0.05 level. Three patients developed mild temporary stress incontinence, two patients developed a short period of temporary blurred vision, and one patient developed temporary excessive vaginal dryness. All adverse events resolved by approximately 4 months. One patient required retreatment followed by successful coitus.ConclusionA multimodal program that treated the physical and psychologic aspects of vaginismus enabled women to achieve pain-free intercourse as noted by patient communications and serial female sexual function studies. Further studies are indicated to better understand the individual components of this multimodal treatment program. Pacik PT, Geletta S. Vaginismus Treatment: Clinical Trials Follow Up 241 Patients. Sex Med 2017;5:e114-e123.
| S-EPMC5440634 | biostudies-literature