Tolerability Of New Drugs Research Articles

Is health-related quality of life (HRQoL) reporting keeping pace with new drug approvals in hematology and oncology: A five-year analysis of 245 drug approvals.

6519 Background: HRQoL data in cancer clinical trials can inform tolerability of new drugs, facilitate informed decision-making, and influence health care and policy decisions, but are frequently underreported. We reviewed all registration trials that informed Food and Drug Administration (FDA) approval between 2015-2020 for latency and quality of HRQoL reporting. Methods: HRQoL data for each clinical trial associated with FDA drug approval between 7/2015-5/2020 was collected retrospectively from multiple sources including the FDA and clinicaltrials.gov website, conference abstracts, and journal manuscripts. The aim of the study was to analyze the proportion of trials reporting HRQoL, quality of HRQoL data, latency between FDA approval and first reporting of HRQoL data, and association between changes in HRQOL and overall survival (OS) and progression-free survival (PFS) outcomes. Results: Of the 259 trials involving 245 drug approvals, majority involved solid tumors (61.4%), were phase III (59.1%), and led to approval based on a non-PFS/OS endpoint (52.9%). HRQoL was a pre-specified endpoint in 55.2% and reported in 49.8% trials. HRQoL data was published by the time of FDA approval in only 41.8% cases, 24.8% reported HRQoL data > 12 mo after approval. Further, among trials reporting HRQoL (n = 129), HRQoL data was first reported in the primary paper in only 34.1%, and either in an ancillary paper in 41.9% or an ancillary abstract in 24% trials. Of the 129 trials with HRQoL data, an improvement in HRQoL was seen in 44.2%, no significant change in 41.9%, mixed results in 11.6%, and worsening in 2.3% of trials. Overall, by the time of FDA approval, OS and PFS data were reported in 59% (152/259) and 65% (168/259) trials respectively with an OS benefit seen in 23.9% (62/259) trials, and PFS benefit in 38.6% (100/259) trials. Of the 84 trials that led to FDA approvals based solely on response rate, HRQoL was reported in only 23.8% (n = 24) with a HRQoL benefit seen in only 9.5% (n = 8) trials. Trials reporting either no significant impact on HRQoL or a mixed impact on HRQoL reported median OS benefit of 4.6 months and 4.2 months respectively. In trials reporting HRQoL data > 6 mo from FDA approval, OS benefit of < 3 mo was seen in 17.8% (8/45) trials. No significant time trends were noted during the study period. Conclusions: There was significant underreporting of HRQoL outcomes in trials ( < 50%) associated with FDA drug approvals between 2015-2020 with majority of trials reporting HRQoL data in an ancillary paper/abstract, and at a much later time than the FDA approval. While it is widely accepted that timely dissemination of HRQoL data from cancer drug trials are vital for clinical and regulatory decisions, no improvement in reporting rates were noted over past 5 years. Only 10% of drugs approved on the basis of response rates showed improvement in HRQoL in the registration trials.

Systematic evaluation of clinical trial protocols of new drugs as a cure of chronic hepatitis B

Objective: To describe the current status of registration and design characteristics of clinical trials of new drugs for curing hepatitis B through domestic and foreign websites, so as to provide references for the follow-up clinical trials of new hepatitis B drugs. Methods: A search was conducted on the US Clinical Trials Database and the Chinese Clinical Trial Registry Center. The search date was from the establishment of the database to May 26, 2020, and the registration trials of new drugs for curing hepatitis B at home and abroad were included. Two researchers independently searched and screened the literature and extracted the data. Results: A total of 106 registered clinical trials of new drugs for curing hepatitis B were included (94 English registration websites and 12 Chinese registration websites), and the number of registrations had increased year by year. Among them, the proportion of therapeutic vaccines and core protein inhibitors were the highest, accounting for 27.4% (n = 29) and 22.6% (n = 24), respectively. The vast majority of clinical trials (n = 96, 90.6%) were in the early stages (Phase I and II). The subjects in phase I clinical trial were mainly healthy people and treated CHB patients, while the subjects in phase II clinical trial were mainly CHB patients who had achieved viral suppression after initial or post-treatment. The main evaluation indicators of Phase I clinical trials were the safety and tolerability of new drugs. The main evaluation indicators in about half of Phase II clinical trials were HBsAg negative conversion/quantitative decline. Overall, the number of clinical trials with the new design was small, accounting for 3.8% (4 / 106). There were relatively few trials of new drugs for curing hepatitis B on domestic registration websites, and the information provided was incomplete. Conclusion: The number of clinical trials of new hepatitis B drugs at home and abroad is increasing year by year, but most of them are in phase I and II, with few adopting new designs. In addition, the information integrity of the domestic website registration center needs to be improved.

Current requirements for studies of drugs for the pathogenetic treatment of multiple sclerosis

More than 10 multiple sclerosis-modifying drugs (MSMDs) are widely used now. Novel MSMDs should be investigated in strict accordance with the evidence-based medicine principles governing clinical trials (of both original drugs and their analogues) that prove the high efficiency, safety, and tolerability of new drugs versus the already existing ones. Russia has gained extensive experience in conducting such studies using the well-known drugs as a comparison group. The efficiency and safety of new therapy should be evaluated according to the international criteria on the basis of a sufficient number of patients during a long-term follow-up. When combining the drugs, their efficiency and the risk of adverse effects can vary. The published results of a small study of the combined drug Leucovir (Belarus) do not meet these requirements, and the possibility of using this drug to treat multiple sclerosis can be discussed only after adequate phases II and III clinical trials.

P2.16-38 Efficacy and Safety of Target Therapy and Immunotherapy in Advanced NSCLC in Elderly: A Systematic Review of Real World Studies

Despite notable advances, treatment of advanced non small cell lung cancer (NSCLC) in the elderly remains a challenge. Target therapy and immunotherapy outcomes have been demonstrated in several randomized controlled trials (RCT), however real world setting may closely mirrors everyday clinical practice in elderly population, characterized by poor performance status, significant comorbidities, concomitant treatments, limited adherence and compliance. Systematic review was conducted to examine the published real-world studies evaluating efficacy and safety of target therapy and immunotherapy in elderly patients with advanced NSCLC. These real-world data were compared to those obtained in the phase II and III randomized controlled trials. Following PRISMA guidelines, in February 2019 we searched the MEDLINE, Web of Science, and Scopus databases in English language. Titles and abstracts were reviewed by 2 independent reviewers (FT; FV); disagreements were resolved by a third. All identified full papers were assessed independently by three researchers (FT, FV, and AV). Included studies were required to be RWS, and evaluate target therapy or immunotherapy in advanced NSCLC elderly patients. The Newcastle Ottawa Scale (NOS) was used for quality assessment of studies included in the systematic review. We found 235 studies through the database, 167 remained after duplicate removal and 24 full-text articles were assessed for eligibility (Figure 1). The systematic search of the literature identified 9 studies meeting the selection criteria to analyse in qualitative synthesis. These studies included a total of 1882 elderly patients mainly treated with first-generation EGFR tyrosine-kinase inhibitors (5 studies), osimertinib only in one study. Bevacizumab in association with chemotherapy was evaluated in two studied. Immunotherapy data was available only in one study. Clinical characteristics of each study population are analyzed. The first relevant aspect is the lack of data on Multidimensional Geriatric Assessment and Charlson Comorbidity Index, that should represent main instruments in clinical practice to personalize therapeutic approach. Heterogeneity of first-generation EGFR TKI efficacy among the studies could be influenced by genetic differences among ethnic groups. In general, the results showed that PFS of patients with advanced NSCLC treated with first-generation EGFR TKI in the real world setting were consistent with those observed in clinical trials, while an inferior survival was recorded. Collected toxicity data were limited. RWS represent a broad picture of the activity and tolerability of new drugs and can provide interesting observations and research ideas in several settings, particularly in elderly patients, integrating and defining data of the RCTs.

Clinical Experience With Perampanel for Refractory Pediatric Epilepsy in One Canadian Center.

Perampanel (PER) is a new antiseizure medication that inhibits the α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) class of glutamate receptors. It is important for physicians to be aware of the efficacy and tolerability of new drugs in the postmarketing phase. We performed a retrospective review of our experience with perampanel at BC Children's Hospital. Twenty-four pediatric patients prescribed perampanel from 2014 to 2016 were identified. Fifteen (63%) discontinued perampanel, and 10 (42%) had greater than 50% reduction in seizures. Twelve (50%) had behavioral and 8 (33%) had nonbehavioral adverse events. One-third experienced serious adverse events. One patient experienced oculogyric crisis, which is not previously reported with perampanel. Adverse events were not dose related and were reversible. Possible risk factors for behavioral adverse events include a history of behavioral problems with other antiseizure medications and preexisting behavioral comorbidities. It is important to counsel patients about the potential for serious adverse events, particularly behavioral, when prescribing perampanel.

Child neuropsychopharmacology: good news… the glass is half full

Child neuropsychopharmacology: good news… the glass is half full

New pharmacological interventions for overactive bladder

This review article assesses the currently available data on new drugs used on and off license for overactive bladder, highlighting the range of pharmacological options. The drugs being considered are solifenacin, darifenacin, transdermal oxybutynin, modified-release propiverine, intravesical botulinum toxin, duloxetine and desmopressin. Although these agents encompass several different modes of action, there is still little evidence to help decide which agent might suit which patient. Furthermore, there have been limited head-to-head studies comparing the efficacy and tolerability of newer drugs. The article concludes with a speculative 5-year view of future developments in the pharmacology of overactive bladder.