Ethics in Clinical Studies: The Dilemma of very Young and Old

The objectives of the research are to percolate knowledge which can improve health and improve understanding of human physiology. Pervasive exclusion of children and elderly in clinical trials as is happening today is not justified. Children have different physiology and pharmacology from adults; often adverse effects are also different and specific. Diseases like neonatal hyperbilirubinemia, infantile spasms are very age specific. Elderly too, have age specific issues like dementias, malignancies, weakened systems and polypharmacy that make them a special cohort. Clinical trials in these age groups are essential so as to gather comprehensive data about a medication across all age groups. Informed consent is a challenge in both these groups. It can be remedied by obtaining consent from parents, or legally acceptable representative in case of children and care givers and/or LARs in case of the elderly. Oral assent from 7 to 11 years, and written assent from 12 to 18 years and in the elderly, along with consent from the LAR, parents, care givers as the case may be, forms the bedrock of good clinical trial ethics.

Safety and Effectiveness of Oral Methylprednisolone Therapy in Comparison With Intramuscular Adrenocorticotropic Hormone and Oral Prednisolone in Children With Infantile Spasms

Background and Purpose: To assess the safety and effectiveness of oral methylprednisolone (oMP) in comparison with intramuscular adrenocorticotropic hormone (imACTH) and oral prednisolone (oP) therapies in children with infantile spasms (IS).Methods: In this prospective, open-label, non-blinded, uncontrolled observational study, children (aged 2–24 months) with newly diagnosed IS presenting with hypsarrhythmia or its variants on electroencephalogram (EEG) were included. It was followed by imACTH, oP, or oMP (32–48 mg/day for 2 weeks followed by tapering) treatments. Electroclinical remission/spasm control, relapse, and adverse effects were evaluated in the short-term (days 14 and 42) and intermediary-term (3, 6, and 12 months) intervals.Results: A total of 320 pediatric patients were enrolled: 108, 107, and 105 in the imACTH, oMP, and oP groups, respectively. The proportion of children achieving electroclinical remission on days 14 and 42 was similar among the three groups (day 14: 53.70 vs. 60.75 vs. 51.43%, p = 0.362; day 42: 57.55 vs. 63.46 vs. 55.34%, p = 0.470). The time to response was significantly faster in the oMP group (6.5 [3.00, 10.00] days vs. 8.00 [5.00, 11.00] days for imACTH and 8.00 [5.00, 13.00] days for oP, p = 0.025). Spasm control at 3, 6, and 12 months was also similar in the three groups (P = 0.775, 0.667, and 0.779). The relapse rate in the imACTH group (24.10%) was lower than oMP (30.77%) and oP groups (33.33%), and the time taken for relapse in the imACTH group (79.00 [56.50, 152.00] days) was longer than oMP (62.50 [38.00, 121.75] days) and oP groups (71.50 [40.00, 99.75] days), but the differences were not statistically significant (p = 0.539 and 0.530, respectively). The occurrence of adverse effects was similar among the three groups.Conclusions: The short and intermediary-term efficacy and recurrence rates of oMP are not inferior to those of imACTH and oP for the treatment of IS. Significantly, the time to achieve electroclinical remission with oMP was quicker than that with imACTH and oP. Considering its convenience, affordability, and the absence of irreversible side effects, oMP can serve as a form of first-line treatment for newly diagnosed IS.

Trends and Costs Associated With the Diagnosis and Treatment of Infantile Spasms: A 10-Year Multicenter Retrospective Review

OBJECTIVE Early treatment of infantile spasms (IS) may be imperative for improvement of neurodevelopmental outcomes. Existing studies have led to inconclusive recommendations with variation in treatment. Our objective was to determine the national average cost, initial diagnostic workup, treatments, and hospital length of stay for patients with IS. METHODS This retrospective cohort study was designed to review data of patients < 2 years from 43 non-profit institutions. Data obtained included patient demographics, length of stay, admission cost, and treatments used from 2004 to 2014. Cost data were collected and adjusted to 2014 dollars, the year data were analyzed. RESULTS A total of 6183 patients met study criteria (n = 3382, 55% male). Three-quarters of patients (n = 4684, 76%) had an electroencephalogram, 56.4% had brain imaging (n = 3487), and 17% (n = 1050) underwent a lumbar puncture. Medication for IS was initiated during inpatient hospital stay in two-thirds of all patients (n = 4139, 67%). Most patients were initiated on corticotropin (n = 2066, 33%) or topiramate (n = 1804, 29%). Average length of stay was 5.8 days with an average adjusted cost of $18,348. Over time there was an 86.6% increase in cost from an average $12,534.54 (2004) to $23,391.20 (2014), a significant change (p < 0.01). This correlated with an increase in average length of stay. CONCLUSIONS Variability exists in diagnostic workup and pharmacotherapy initiated for IS, which may lead to differences in the cost of hospital stay. Further studies may help determine contributing factors to increased cost and improve health care utilization for IS patients.

P.097 Adrenal Insufficiency among Children treated with Hormonal Therapy for Infantile Spasms

Background: Hormonal therapy is a standard treatment for infantile spasms. The high doses given and long treatment duration expose patients to the risk of adrenal insufficiency (AI). This study aims to quantify the incidence of AI among children with infantile spasms treated with corticosteroids and/or adrenocorticotropic hormone (ACTH). Methods: A retrospective chart review of patients treated for infantile spasms was performed between January 2009 to March 2020 in one pediatric specialized hospital. Variables collected included patient and treatment characteristics, risk factors of AI and adrenal function testing. Analysis included descriptive statistics. Results: Thirty-one patients met the inclusion criteria and received a total of 33 separated courses of treatment. Adrenal function following each course of treatment was evaluated in all patients. AI occurred in 25/33 (76% [95CI 58-89]) children. There was no predictive factor of AI. No drug regimen was deemed safe. The two patients (6%) with an acute adrenal crisis were the youngest of the cohort. Conclusions: Adrenal suppression is frequent and can lead to adrenal crisis after standard hormonal therapy for infantile spasms. A routine laboratory assessment of adrenal function should be done for all patients. Hydrocortisone replacement therapy should be given until testing results are obtained, particularly for younger infants.

GP.6 Improving Triaging of EEG Referrals for Rule out Infantile Spasms (ITERIS)

Background: Infantile spasms (IS) is a devastating pediatric seizure disorder for which EEG referrals are prioritized at the Hospital for Sick Children, representing a resource challenge. The goal of this study was to improve the triaging system for these referrals. Methods: Part 1: descriptive analysis was performed retrospectively on EEG referrals. Part 2: prospective questionnaires were used to determine relative risk of various predictive factors. Part 3: electronic referral form was amended to include 5 positive predictive factors. A triage point system was tested by assigning EEGs as high risk (3 days), standard risk (1 week), or low risk (2 weeks). A machine learning model was developed. Results: Most EEG referrals were from community pediatricians with a low yield of IS diagnoses. Using the 5 predictive factors, the proposed triage system accurately diagnosed all IS within 3 days. No abnormal EEGs were missed in the low-risk category. The machine learning model had over 90% predictive accuracy and will be prospectively tested. Conclusions: Improving EEG triaging for IS may be possible to prioritize higher risk patients. Machine Learning techniques can potentially be applied to help with predictions. We hope that our findings will ultimately improve resource utilization and patient care.