Martin Offringa - Academia.edu (original) (raw)

Papers by Martin Offringa

reporting items in pediatric clinical trial protocols and reports: two systematic reviews

BackgroundBayesian methods are increasing in popularity in clinical research. The design of Bayes... more BackgroundBayesian methods are increasing in popularity in clinical research. The design of Bayesian clinical trials requires a prior distribution, which can be elicited from experts. Current elicitation approaches either use face-to-face sessions or expert surveys. In diseases with international differences in management, the elicitation exercise should recruit internationally, requiring expensive face-to-face sessions or surveys, which suffer low response rates. To address this, we developed a remote, real-time elicitation exercise to construct prior distributions. These elicited distributions were then used to determine the sample size of the Bronchiolitis in Infants with Placebo Versus Epinephrine and Dexamethasone (BIPED) Study, an international randomized controlled trial trial in the Pediatric Emergency Research Network (PERN). The BIPED study aims to determine whether the combination of epinephrine and dexamethasone, compared to placebo, is effective in reducing hospital adm...

Trials, 2020

Background Acute gastroenteritis is a leading cause of emergency department visits and hospitaliz... more Background Acute gastroenteritis is a leading cause of emergency department visits and hospitalizations among children in North America. Oral-rehydration therapy is recommended for children with mild-to-moderate dehydration, but children who present with vomiting are frequently offered intravenous rehydration in the emergency department (ED). Recent studies have demonstrated that the anti-emetic ondansetron can reduce vomiting, intravenous rehydration, and hospitalization when administered in the ED to children with dehydration. However, there is little evidence of additional benefit from prescribing ondansetron beyond the initial ED dose. Moreover, repeat dosing may increase the frequency of diarrhea. Despite the lack of evidence and potential adverse side effects, many physicians across North America provide multiple doses of ondansetron to be taken following ED disposition. Thus, the Multi-Dose Oral Ondansetron for Pediatric Gastroenteritis (DOSE-AGE) trial will evaluate the effe...

SSRN Electronic Journal, 2020

Background: Our double-blind, placebo-controlled, randomised trial investigating systemic hydroco... more Background: Our double-blind, placebo-controlled, randomised trial investigating systemic hydrocortisone in mechanically ventilated preterm infants (gestational age <30 weeks and/or birth weight <1250 grams) in the second week of life, reported no difference for the primary outcome death or bronchopulmonary dysplasia (BPD) at 36 weeks’ postmenstrual age. Here we report the results for death and neurodevelopmental impairment (NDI) at two years’ corrected age (CA). Methods: The infants were randomly assigned to a 22-day course of systemic hydrocortisone (cumulative dose 72∙5 mg/kg; n=182) or placebo (n=190) stratified by study centre and gestational age (<27, ≥27 weeks). Follow-up assessment was performed in the 16 neonatal trial centres at 2 years’ CA. Findings: Among 371 patients (mean gestational age 26 weeks) who completed the trial, 276 (74∙4%) survived till 2 years’ CA, and were assessed between April 18, 2014 and June, 27 2019; parents withdrew consent for one child treated with hydrocortisone. The composite outcome death or NDI was available in 356 (96∙0%) infants and occurred in 97 of 171 hydrocortisone treated infants (56∙7%), and in 116 of 185 infants (62∙7%) assigned to placebo (adjusted risk difference, -5∙2% [95% CI -15∙1 to 4∙6]; adjusted odds ratio, 0∙79 [95% CI 0∙51 to 1∙22], p=0∙28). Pre-specified subgroup analysis of infants <27 weeks gestation showed a significant reduction in death or NDI in the hydrocortisone group compared to the placebo group (54∙6% vs. 66∙2%; risk difference -11∙6% [95% CI -22∙4% to -0∙5%], p=0∙02 for interaction). Interpretation: The administration of hydrocortisone in the second week of life was not significantly associated with a difference in death or NDI in mechanically ventilated preterm infants. Future studies should confirm the observed increased intact survival in infants <27 weeks gestation treated with systemic hydrocortisone. Trial Registration: The SToP-BPD study was registered with The Netherlands Trial Register (NTR2768; registered on 17 February 2011) and the European Union Clinical Trials Register (EudraCT, 2010-023777-19; registered on 2 November 2010). Funding Statement: The Netherlands Organization for Health Research and Development ZonMW Priority Medicines for Children no. 11-32010-02. Declaration of Interests: Dr. van Kaam reports grants from The Netherlands Organization for Health Research and Development ZonMW during the conduct of the study. No other disclosures were reported. Ethics Approval Statement: The study-protocol was approved by the human research ethics committees at each participating centre. Written informed consent was obtained from both parents before randomisation.

Children, 2020

Policy has been developed to promote the conduct of high-quality pediatric randomized controlled ... more Policy has been developed to promote the conduct of high-quality pediatric randomized controlled trials (RCTs). Whether these strategies have influenced publication trends in high-impact journals is unknown. We aim to evaluate characteristics, citation patterns, and publication trends of pediatric RCTs published in general medical journals (GMJs) compared with adult RCTs over a 13-year period. Studies were identified using Medline, and impact metrics were collected from Web of Science and Scopus. All RCTs published from 2005–2018 in 7 GMJs with the highest impact factors were identified for analysis. A random sample of matched pediatric and adult RCTs were assessed for publication characteristics, academic and non-academic citation. Citations were counted from publication until June 2019. Among 4146 RCTs, 2794 (67.3%) enrolled adults, 591 (14.2%) enrolled children, and 761 RCTs (18.3%) enrolled adult and pediatric patients. Adult RCTs published in GMJs grew by 5.1 publications per y...

New England Journal of Medicine, 2020

BACKGROUND Worldwide, many newborns who are preterm, small or large for gestational age, or born ... more BACKGROUND Worldwide, many newborns who are preterm, small or large for gestational age, or born to mothers with diabetes are screened for hypoglycemia, with a goal of preventing brain injury. However, there is no consensus on a treatment threshold that is safe but also avoids overtreatment. METHODS In a multicenter, randomized, noninferiority trial involving 689 otherwise healthy newborns born at 35 weeks of gestation or later and identified as being at risk for hypoglycemia, we compared two threshold values for treatment of asymptomatic moderate hypoglycemia. We sought to determine whether a management strategy that used a lower threshold (treatment administered at a glucose concentration of <36 mg per deciliter [2.0 mmol per liter]) would be noninferior to a traditional threshold (treatment at a glucose concentration of <47 mg per deciliter [2.6 mmol per liter]) with respect to psychomotor development at 18 months, assessed with the Bayley Scales of Infant and Toddler Development, third edition, Dutch version (Bayley-III-NL; scores range from 50 to 150 [mean {±SD}, 100±15]), with higher scores indicating more advanced development and 7.5 points (one half the SD) representing a clinically important difference). The lower threshold would be considered noninferior if scores were less than 7.5 points lower than scores in the traditional-threshold group. RESULTS Bayley-III-NL scores were assessed in 287 of the 348 children (82.5%) in the lower-threshold group and in 295 of the 341 children (86.5%) in the traditional-threshold group. Cognitive and motor outcome scores were similar in the two groups (mean scores [±SE], 102.9±0.7 [cognitive] and 104.6±0.7 [motor] in the lower-threshold group and 102.2±0.7 [cognitive] and 104.9±0.7 [motor] in the traditional-threshold group). The prespecified inferiority limit was not crossed. The mean glucose concentration was 57±0.4 mg per deciliter (3.2±0.02 mmol per liter) in the lower-threshold group and 61±0.5 mg per deciliter (3.4±0.03 mmol per liter) in the traditional-threshold group. Fewer and less severe hypoglycemic episodes occurred in the traditional-threshold group, but that group had more invasive diagnostic and treatment interventions. Serious adverse events in the lower-threshold group included convulsions (during normoglycemia) in one newborn and one death. CONCLUSIONS In otherwise healthy newborns with asymptomatic moderate hypoglycemia, a lower glucose treatment threshold (36 mg per deciliter) was noninferior to a traditional threshold (47 mg per deciliter) with regard to psychomotor development at 18 months. (Funded by the Netherlands Organization for Health Research and Development; HypoEXIT Current Controlled Trials number, ISRCTN79705768.

Background: Evidence-based health care is informed by results of randomized clinical trials (RCTs... more Background: Evidence-based health care is informed by results of randomized clinical trials (RCTs) and their syntheses in meta-analyses. When the trial outcomes measured are not clearly described in trial publications, knowledge synthesis, translation, and decision-making may be impeded. While heterogeneity in outcomes measured in adolescent major depressive disorder (MDD) RCTs has been described, the comprehensiveness of outcome reporting is unknown. This study aimed to assess the reporting of primary outcomes in RCTs evaluating treatments for adolescent MDD. Methods: RCTs evaluating treatment interventions in adolescents with a diagnosis of MDD published between 2008 and 2017 specifying a single primary outcome were eligible for outcome reporting assessment. Outcome reporting assessment was done independently in duplicate using a comprehensive checklist of 58 reporting items. Primary outcome information provided in each RCT publication was scored as "fully reported", "partially reported", or "not reported" for each checklist item, as applicable. Results: Eighteen of 42 identified articles were found to have a discernable single primary outcome and were included for outcome reporting assessment. Most trials (72%) did not fully report on over half of the 58 checklist items. Items describing masking of outcome assessors, timing and frequency of outcome assessment, and outcome analyses were fully reported in over 70% of trials. Items less frequently reported included outcome measurement instrument properties (ranging from 6 to 17%), justification of timing and frequency of outcome assessment (6%), and justification of criteria used for clinically significant differences (17%). The overall comprehensiveness of reporting appeared stable over time. Conclusions: Heterogeneous reporting exists in published adolescent MDD RCTs, with frequent omissions of key details about their primary outcomes. These omissions may impair interpretability, replicability, and synthesis of RCTs that inform clinical guidelines and decision-making in this field. Consensus on the minimal criteria for outcome reporting in adolescent MDD RCTs is needed.

Tijdschrift voor kindergeneeskunde, 2003

... vrij consequent de term 'quality of life' hanteert, worden 'kwaliteit van leve... more ... vrij consequent de term 'quality of life' hanteert, worden 'kwaliteit van leven' en ' gezondheidsbeleving' in de Nederlandse litera-tuur nogal door ... een lage score in het domein rolbeperkingen als gevolg van emotionele problemen minder prevalent dan in de normpopulatie ( ...

Pediatric Research, 2018

BACKGROUND: In pediatric medicine, the usual treatment received by children ("standard of care") ... more BACKGROUND: In pediatric medicine, the usual treatment received by children ("standard of care") varies across centers. Evaluations of new treatments often compare to the existing "standard of care" to determine if a treatment is more effective, has a better safety profile, or costs less. The objective of our study was to evaluate intervention and "standard of care" control arms reported in published pediatric clinical trials. METHODS: Pediatric clinical trials, published in 2014, reporting the use of a "standard of care" control arm were included. Duplicate assessment of reporting completeness was done using the 12-item TIDieR (Template for Intervention Description and Replication) checklist for both the "standard of care" control arms and intervention arms within the same published study. RESULTS: Following screening, 214 pediatric trials in diverse therapeutic areas were included. Several different terms were used to describe "standard of care." There was a significant difference between the mean reported TIDieR checklist items of "standard of care" control arms (5.81 (SD 2.13) and intervention arms (8.45 (SD 1.39, p < 0.0001). CONCLUSIONS: Reporting of intervention and "standard of care" control arms in pediatric clinical trials should be improved as current "standard of care" reporting deficiencies limit reproducibility of research and may ultimately contribute to research waste.

CMAJ open, Jan 26, 2018

Worldwide, many countries have developed a list of essential medicines for children to improve pr... more Worldwide, many countries have developed a list of essential medicines for children to improve prescribing. We aimed to create an essential medicines list for children in Canada. We adapted the previously created preliminary list of essential medicines for adults in Canada and the WHO Model List of Essential Medicines for Children to create a provisional list of essential medicines for children in Canada. Canadian clinicians made suggestions for changes. Literature relevant to each suggestion was presented to clinician-scientists, who used a modified nominal group technique to make recommendations on the suggestions. Ontario Public Drug Programs prescription data were reviewed to identify commonly prescribed medications missing from the list. Literature relevant to these medications was shared with a clinician-scientist review panel to determine which should be added, and a revised list was developed. A total of 76 items were removed from the list of essential medicines for adults i...

Journal of clinical epidemiology, 2018

Evaluate comparative harm rates from medical interventions in pediatric randomized clinical trial... more Evaluate comparative harm rates from medical interventions in pediatric randomized clinical trials (RCTs) from more developed (MDCs) and less developed countries (LDCs). Meta-epidemiologic empirical evaluation of Cochrane Database of Systematic Reviews (June 2014) meta-analyses reporting clinically important harm-outcomes (severe adverse events [AEs], discontinuations due to AEs, any AE, and mortality) that included at least one pediatric RCT from MDCs and at least one from LDCs. We estimated relative odds ratios (RORs) for each harm, within each meta-analysis, between RCTs from MDCs and LDCs and calculated random-effects-summary-RORs (sRORs) for each harm across multiple meta-analyses. Only 1% (26/2,363) of meta-analyses with clinically important harm-outcomes in the entire Cochrane Database of Systematic Reviews included pediatric RCTs both from MDCs and LDCs. We analyzed 26 meta-analyses with 244 data sets from pediatric RCTs, 116 from MDCs and 128 from LDCs (64 and 66 unique RCT...

Tijdschrift voor kindergeneeskunde, 2007

BMJ Paediatrics Open, 2017

versus non-operative treatment for acute uncomplicated appendicitis in children: study protocol f... more versus non-operative treatment for acute uncomplicated appendicitis in children: study protocol for a multicentre, open-label, non-inferiority, randomised controlled trial.

Journal of Clinical Oncology, 1999

PURPOSE: To determine the value of indium-111–antimyosin (111In-AM) scintigraphy in the early det... more PURPOSE: To determine the value of indium-111–antimyosin (111In-AM) scintigraphy in the early detection of myocardial damage in children treated with doxorubicin. PATIENTS AND METHODS: Twelve planar scintigrams were made of eight patients (seven children and one young adult; mean age, 12 years). Three scans were obtained before doxorubicin therapy in three patients, and nine scans were obtained during doxorubicin therapy in seven patients. The heart-to-lung ratio (HLR) was calculated. Left ventricular function was assessed by echocardiography before and during therapy by measuring the fractional shortening (FS). RESULTS: The HLR of the three baseline scans was below 1.5, within the normal range for adults. Six of the seven patients whose scans were obtained during chemotherapy had abnormal HLR values (> 1.5). One patient had severe myocyte damage and showed an early increase in the HLR (2.3) after a cumulative doxorubicin dose of 150 mg/m2. The FS measured by echocardiography was...

BMC pediatrics, Jan 6, 2017

Systematic reviews are key tools to enable decision making by healthcare providers and policymake... more Systematic reviews are key tools to enable decision making by healthcare providers and policymakers. Despite the availability of the evidence based Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA-2009 and PRISMA-P 2015) statements that were developed to improve the transparency and quality of reporting of systematic reviews, uncertainty on how to deal with pediatric-specific methodological challenges of systematic reviews impairs decision-making in child health. In this paper, we identify methodological challenges specific to the design, conduct and reporting of pediatric systematic reviews, and propose a process to address these challenges. One fundamental decision at the outset of a systematic review is whether to focus on a pediatric population only, or to include both adult and pediatric populations. Both from the policy and patient care point of view, the appropriateness of interventions and comparators administered to pre-defined pediatric age subgro...

Trials, 2016

Background: The prevalence of neonatal abstinence syndrome (NAS) is increasing globally resulting... more Background: The prevalence of neonatal abstinence syndrome (NAS) is increasing globally resulting in an increased incidence of adverse neonatal outcomes and health system costs. Evidence regarding the effectiveness of NAS prevention and management strategies is very weak and further research initiatives are critically needed to support meta-analysis and clinical practice guidelines. In NAS research, the choice of outcomes and the use of valid, responsive and feasible measurement instruments are crucial. There is currently no consensus and evidence-based core outcome set (COS) for NAS. Methods/design: The development of the NAS-COS will include five stages led by an international Multidisciplinary Steering Committee: (1) qualitative interviews with parents/families and a systematic review (SR) to identify items for inclusion in a COS. The SR will also identify participants for the Delphi survey, (2) a three-round Delphi survey to gain expert opinion on the importance of health outcomes influencing NAS management decisions, (3), a consensus meeting to finalize the items and definitions with experts and COS users, (4) feasibility and pilot testing, development of the COS and explanatory document and (5) implementation planning. Discussion: Since standardized outcome measurement and reporting will improve NAS clinical research consistency, efficacy and impact, this COS will reflect the minimum set of health outcomes which should be measured in trials evaluating interventions for preventing or treating NAS.

Archives of Disease in Childhood, 2016

As many drugs in paediatrics are used off-label, prescribers face a lack of evidence-based dosing... more As many drugs in paediatrics are used off-label, prescribers face a lack of evidence-based dosing guidelines. A Dutch framework was developed to provide dosing guidelines based on best available evidence from registration data, investigator-initiated research, professional guidelines, clinical experience and consensus. This has clarified the scientific grounds of drug use for children and encouraged uniformity in prescribing habits in the Netherlands. The developed framework and the current content of the Dutch Paediatric Formulary could be used as basis for similar initiatives worldwide, preferably in a concerted effort to ultimately provide children with effective and safe drug therapy.

Klinisch redeneren en evidence-based practice, 2016