Maternal inflammation during pregnancy is associated with risk of ADHD in children at age 10.

INTRODUCTION: Maternal inflammation during pregnancy may affect early neurodevelopment in offspring as suggested by preclinical and register data. However, clinical evidence for risk of aberrant neurodevelopment later in childhood is scarce. In the population-based COPSAC2010 mother-child cohort, we investigated associations between maternal inflammation levels during pregnancy and the risk of a diagnosis of ADHD as well as the load of ADHD symptoms in the children at age 10. METHODS: The COPSAC2010 cohort consists of 700 mother-child pairs followed prospectively since pregnancy week 24.Maternal high-sensitivity C-Reactive Protein (hs-CRP) level at week 24 of gestation was investigated in relation to child neurodevelopment by age 10 using logistic and linear regression models with extensive confounder adjustment, including socioeconomic status and maternal polygenic risk of ADHD. The children completed a comprehensive examination of neurodevelopment including categorical (i.e., diagnostic) and dimensional (i.e., symptom load) psychopathology using the Kiddie Schedule for Affective Disorders and Schizophrenia Present and Lifetime Version (K-SADS-PL) and parental rated ADHD-Rating Scale (ADHD-RS). RESULTS: A total of 604 (86 %) of the 700 children in the COPSAC2010 cohort participated in the COPSYCH visit at age 10. Sixty-five (10.8 %) fulfilled a research diagnosis of ADHD (16 girls and 49 boys). Higher maternal hs-CRP level in pregnancy at week 24 (median 5.4 mg/L) was significantly associated with increased risk for a diagnosis of ADHD, adjusted OR 1.40, 95 %CI (1.16-1.70), p = 0.001. Additionally, higher maternal hs-CRP was associated with increased ADHD symptom load in the entire cohort, reflected by ADHD-RS raw scores. DISCUSSION: These clinical data demonstrated a robust association of prenatal maternal inflammation assessed by hs-CRP with a diagnosis of ADHD by age 10. Moreover, maternal inflammation was associated with ADHD symptom load in the complete cohort. Identifying inflammation as an important marker will provide a potential target for future increased awareness and prevention during pregnancy thereby ultimately improving neurodevelopmental outcomes in children.

Dimensional profiling of psychopathology in children and adolescents based on the K-SADS-PL and an analysis of the construct validity of two ADHD symptom dimensions.

OBJECTIVES: The traditional view on psychiatric disorders as categorical and distinct is being challenged by perspectives emphasizing the relevance of dimensional and transdiagnostic assessment. However, most diagnostic instruments are based on a categorical view with a threshold-approach to disease classification. METHODS: We here describe algorithms for dimensionalizing the psychopathological ratings of the widely used diagnostic interview for children and adolescents, the Kiddie-Schedule for Affective Disorders and Schizophrenia - Present and Lifetime Version (K-SADS-PL). We further evaluate the criterion-related construct validity of the dimensionalized attention-deficit/hyperactivity disorder (ADHD) scales using Rasch models in a sample of 590 children (mean age 10.29 (.36), 49% girls). RESULTS: The algorithms generate scores of current symptom load, i.e., the sum of clinician-rated symptoms within each disorder assessed with the interview. We found support for counting symptoms of inattention and hyperactivity/impulsivity, respectively, but not for a single combined ADHD scale. CONCLUSIONS: The algorithms constitute an initial step in creating a framework for clinician-rated dimensional analyses of symptoms derived from the K-SADS-PL, but future studies are needed to further evaluate the construct validity of the remaining scales and the reliability and clinical utility of the method. We believe that our proposed algorithms offer a novel method of dimensional psychopathological assessment, which can be applied in multiple branches of child and adolescent psychiatry.

Integrating Medical Librarians in Evidence-Based Medical Practice in Africa: A Survey of Current Practices and Challenges.

Librarians' involvement in Evidence-Based Medical Practice (EBMP) has been widely reported from the Global North. The cross-sectional study designed a survey to investigate how African medical librarians integrate into EBMP. The respondents comprised medical librarians from 12 African countries. Findings revealed that African medical librarians are mostly involved in EBMP activities related to resource use, management, and evidence dissemination. The leading EBMP tools reportedly used or promoted by the librarians include UpToDate and Cochrane Library, while the leading challenges encountered in offering support for EBMP are related to skill deficiency, poor funding, and poor internet connectivity.

Identifying COVID-19 Vaccine Deserts and Ways to Reduce Them: A Digital Tool to Support Public Health Decision-Making.

A private-academic partnership built the Vaccine Equity Planner (VEP) to help decision-makers improve geographic access to COVID-19 vaccinations across the United States by identifying vaccine deserts and facilities that could fill those deserts. The VEP presented complex, updated data in an intuitive form during a rapidly changing pandemic situation. The persistence of vaccine deserts in every state as COVID-19 booster recommendations develop suggests that vaccine delivery can be improved. Underresourced public health systems benefit from tools providing real-time, accurate, actionable data. (Am J Public Health. 2023;113(4):363-367. https://doi.org/10.2105/AJPH.2022.307198).

Phase III randomized trial of second-line ixabepilone versus paclitaxel or doxorubicin in women with advanced endometrial cancer.

OBJECTIVE: The purpose of this multicenter, open label, randomized phase III study was to determine whether ixabepilone resulted in improved overall survival (OS) compared with commonly used single-agent chemotherapy (doxorubicin or paclitaxel) in women with locally advanced, recurrent, or metastatic endometrial cancer with at least one failed prior platinum-based chemotherapeutic regimen. METHODS: Patients were randomized 1:1 to ixabepilone (40mg/m(2)), or either paclitaxel (175mg/m(2)) or doxorubicin (60mg/m(2)), every 21days. Patients that had previously received an anthracycline were randomized to ixabepilone or paclitaxel; all other patients were randomized to ixabepilone or doxorubicin. An interim analysis of futility for OS was planned. RESULTS: At the time of database lock, 496 patients were randomized to receive ixabepilone (n=248) or control (n=248); nine patients in the control arm were not treated. The interim analysis of futility for OS (219 events) favored the control chemotherapy arm (hazard ratio=1.3 [95% confidence interval: 1.0-1.7], stratified log rank test P=0.0397), indicating that the study would not meet its primary objective. The study was discontinued based on the interim OS results. The frequency of adverse events was comparable between the treatment arms. CONCLUSIONS: The study did not meet its primary objective of improving OS in the ixabepilone arm compared to the control chemotherapy arm. A favorable risk/benefit ratio was not observed for ixabepilone versus control at the time of the interim analysis. The safety results were consistent with the known safety profiles of ixabepilone and control.

High-dose vitamin D3 supplementation in pregnancy and risk of neurodevelopmental disorders in the children at age 10: A randomized clinical trial.

BACKGROUND: Vitamin D deficiency in pregnancy may increase the risk of autism and attention deficit hyperactivity disorder (ADHD). OBJECTIVE: The objective of this study was to estimate the effect of vitamin D3 supplementation in pregnancy on risk of autism and ADHD. DESIGN: This randomized clinical trial was part of the COpenhagen Prospective Study on Neuro-PSYCHiatric Development (COPYCH) project nested within the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC2010) cohort comprising a population-based sample of 700 healthy mother-child pairs enrolled at week 24 of pregnancy. Maternal 25-hydroxy-vitamin D (25(OH)D) was measured at inclusion and 623 mothers were randomized 1:1 to either high-dose (2800 IU/d) or standard dose (400 IU/d) vitamin D3 until 1 wk postpartum (315 received high-dose, 308 standard dose). At age 10, diagnoses and symptom load of autism and ADHD, respectively, were established using the Kiddie-Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version. RESULTS: The psychopathologic evaluation was completed by 591 children aged 10 y, and 16 children (2.7%) were diagnosed with autism and 65 (11.0%) with ADHD. Hereof, 496 children participated in the vitamin D3 trial (246 received high-dose, 250 standard dose). Of these, 12 children (2.4%) were diagnosed with autism and 58 (11.7%) with ADHD. Higher maternal preintervention 25(OH)D levels were associated with a decreased risk of autism [odd ratio (OR) per 10 nmol/L: 0.76 (0.59,0.97); P = 0.034], lower autistic symptom load [ß per 10 nmol/L: -0.03 (-0.05,0.00); P = 0.024), and decreased risk of ADHD diagnosis (OR per 10 nmol/L: 0.88 (0.78,0.99); P = 0.033]. High-dose vitamin D3 supplementation was not associated with risk of autism or ADHD. CONCLUSIONS: Higher maternal preintervention 25(OH)D was associated with a decreased risk of autism, lower autistic symptom load, and decreased risk of ADHD diagnosis, but high-dose vitamin D3 supplementation in pregnancy had no effect on risk of autism and ADHD. This trial was registered at clinicaltrials.gov as NCT00856947.

A Western Dietary Pattern during Pregnancy is Associated with Neurodevelopmental Disorders in Childhood and Adolescence.

Despite the high prevalence of neurodevelopmental disorders, there is a notable gap in clinical studies exploring the impact of maternal diet during pregnancy on child neurodevelopment. This observational clinical study examined the association between pregnancy dietary patterns and neurodevelopmental disorders, as well as their symptoms, in a prospective cohort of 10-year-old children (n=508). Data-driven dietary patterns were derived from self-reported food frequency questionnaires. A Western dietary pattern in pregnancy (per SD change) was significantly associated with attention-deficit / hyperactivity disorder (ADHD) (OR 1.66 [1.21 - 2.27], p=0.002) and autism diagnosis (OR 2.22 [1.33 - 3.74], p=0.002) and associated symptoms (p<0.001). Findings for ADHD were validated in three large (n=59725, n=656, n=348), independent mother-child cohorts. Objective blood metabolome modelling at 24 weeks gestation identified 15 causally mediating metabolites which significantly improved ADHD prediction in external validation. Temporal analyses across five blood metabolome timepoints in two independent mother-child cohorts revealed that the association of Western dietary pattern metabolite scores with neurodevelopmental outcomes was consistently significant in early to mid-pregnancy, independent of later child timepoints. These findings underscore the importance of early intervention and provide robust evidence for targeted prenatal dietary interventions to prevent neurodevelopmental disorders in children.

COVID-19 lockdown, genetic ADHD susceptibility, and mental health in 10- year-old children.

Previous studies report that the COVID-19 lockdown had an impact on the mental health of the pediatric population. In this study, we harness the deep neuropsychiatric phenotyping of the population-based COPSAC2010 (n = 700) cohort at age 10 to study the impact of the COVID-19 lockdown on mental health outcomes with focus on the role of the genetic vulnerability to attention-deficit/hyperactivity disorder (ADHD), in the form of polygenic risk scores (PRS). A total of 593 children were examined between 2019 and 2021, resulting in two groups of different children, those evaluated before the lockdown (n = 230) and those evaluated after (n = 363). Children assessed after the lockdown presented higher odds of being diagnosed with ADHD and had significantly higher scores in most neuropsychiatric scales, particularly in subscales pertaining to behavior and attention problems. We observed a significant interaction between the lockdown and ADHD PRS on several neuropsychiatric dimensions, with a large post-lockdown increase in children with a high PRS, while there was little to no pre-post difference in children with low PRS. These results indicate mental health consequences of the lockdown in children and suggest that genetically susceptible individuals are more affected by such stressors in childhood.

Barriers and facilitators to use of a digital clinical decision support tool: a cohort study combining clickstream and survey data.

OBJECTIVES: This research aimed to understand the barriers and facilitators clinicians face in using a digital clinical decision support tool-UpToDate-around the globe. DESIGN: We used a mixed-methods cohort study design that enrolled 1681 clinicians (physicians, surgeons or physician assistants) who applied for free access to UpToDate through our established donation programme during a 9-week study enrolment period. Eligibility included working outside of the USA for a limited-resource public or non-profit health facility, serving vulnerable populations, having at least intermittent internet access, completing the application in English; and not being otherwise able to afford the subscription. INTERVENTION: After consenting to study participation, clinicians received a 1-year subscription to UpToDate. They completed a series of surveys over the year, and we collected clickstream data tracking their use of the tool. PRIMARY AND SECONDARY OUTCOME MEASURES: (1) The variation in use by demographic; (2) the prevalence of barriers and facilitators of use; and (3) the relationship between barriers, facilitators and use. RESULTS: Of 1681 study enrollees, 69% were men and 71% were between 25 and 35 years old, with the plurality practicing general medicine and the majority in sub-Saharan Africa or Southeast Asia. Of the 11 barriers we assessed, fitting the tool into the workflow was a statistically significant barrier, making clinicians 50% less likely to use it. Of the 10 facilitators we assessed, a supportive professional context and utility were significant drivers of use. CONCLUSIONS: There are several clear barriers and facilitators to promoting the use of digital clinical decision support tools in practice. We recommend tools like UpToDate be implemented with complementary services. These include generating a supportive professional context, helping clinicians realise the tools' use and working with health systems to better integrate digital, clinical decision support tools into workflows.

Segmenting Clinicians' Usage Patterns of a Digital Health Tool in Resource-Limited Settings: Clickstream Data Analysis and Survey Study.

BACKGROUND: Evidence-based digital health tools allow clinicians to keep up with the expanding medical literature and provide safer and more accurate care. Understanding users' online behavior in low-resource settings can inform programs that encourage the use of such tools. Our program collaborates with digital tool providers, including UpToDate, to facilitate free subscriptions for clinicians serving in low-resource settings globally. OBJECTIVE: We aimed to define segments of clinicians based on their usage patterns of UpToDate, describe the demographics of those segments, and relate the segments to self-reported professional climate measures. METHODS: We collected 12 months of clickstream data (a record of users' clicks within the tool) as well as repeated surveys. We calculated the total number of sessions, time spent online, type of activity (navigating, reading, or account management), calendar period of use, percentage of days active online, and minutes of use per active day. We defined behavioral segments based on the distributions of these statistics and related them to survey data. RESULTS: We enrolled 1681 clinicians from 75 countries over a 9-week period. We based the following five behavioral segments on the length and intensity of use: short-term, light users (420/1681, 25%); short-term, heavy users (252/1681, 15%); long-term, heavy users (403/1681, 24%); long-term, light users (370/1681, 22%); and never-users (252/1681, 15%). Users spent a median of 5 hours using the tool over the year. On days when users logged on, they spent a median of 4.4 minutes online and an average of 71% of their time reading medical content as opposed to navigating or managing their account. Over half (773/1432, 54%) of the users actively used the tool for 48 weeks or more during the 52-week study period. The distribution of segments varied by age, with lighter and less use among those aged 35 years or older compared to that among younger users. The speciality of medicine had the heaviest use, and emergency medicine had the lightest use. Segments varied strongly by geographic region. As for professional climate, most respondents (1429/1681, 85%) reported that clinicians in their area would view the use of a online tool positively, and compared to those who reported other views, these respondents were less likely to be never-users (286/1681, 17% vs 387/1681, 23%) and more likely to be long-term users (655/1681, 39% vs 370/1681, 22%). CONCLUSIONS: We believe that these behavioral segments can help inform the implementation of digital health tools, identify users who may need assistance, tailor training and messaging for users, and support research on digital health efforts. Methods for combining clickstream data with demographic and survey data have the potential to inform global health implementation. Our forthcoming analysis will use these methods to better elucidate what drives digital health tool use.

Effects of prenatal nutrient supplementation and early life exposures on neurodevelopment at age 10: a randomised controlled trial - the COPSYCH study protocol.

INTRODUCTION: Nutrient deficiency and immune and inflammatory disturbances in early life may compromise neurodevelopment and be implicated in the aetiology of psychiatric disorders. However, current evidence is limited by its predominantly observational nature. COpenhagen Prospective Study on Neuro-PSYCHiatric Development (COPSYCH) is a research alliance between Copenhagen Prospective Studies on Asthma in Childhood (COPSAC) and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research with the overall aim to investigate effects of prenatal and early life exposures on neurodevelopment at 10 years. COPSYCH will investigate the impact of prenatal n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) and high-dose vitamin D supplementation on neurodevelopment reflected by brain development, neurocognition and psychopathology. Moreover, the neurodevelopmental impact of early life exposures such as infections, low grade inflammation and the gut microbiome will be scrutinised. METHODS AND ANALYSIS: COPSYCH is based on the prospective and ongoing COPSAC2010 birth cohort of 700 mother-child pairs. Randomised controlled trials of supplementation with n-3 LCPUFA and/or high-dose vitamin D or placebo in the third trimester were embedded in a factorial 2×2 design (ClinicalTrials.gov: NCT01233297 and NCT00856947). This unique cohort provides deep phenotyping data from 14 previous clinical follow-up visits and exposure assessments since birth. The ongoing 10-year visit is a 2-day visit. Day 1 includes a comprehensive neurocognitive examination, and assessment of psychopathological dimensions, and assessment of categorical psychopathology. Day 2 includes acquisition of brain structural, diffusion and functional sequences using 3 Tesla MRI. Study outcomes are neurocognitive, psychopathological and MRI measures. ETHICS AND DISSEMINATION: This study has been approved by the Danish National Committee on Health Research Ethics and The Danish Data Protection Agency. The study is conducted in accordance with the guiding principles of the Declaration of Helsinki. Parents gave written informed consent before enrolment.

Utilization and uptake of the UpToDate clinical decision support tool at the Makerere University College of Health Sciences (MakCHS), Uganda.

BACKGROUND: The use of point-of-care, evidence-based tools is becoming increasingly popular. They can provide easy-touse, high-quality information which is regularly updated and has been shown to improve clinical outcomes. Integrating such tools into clinical practice is an important component of improving the quality of health care. However, because such tools are rarely used in resource-limited settings, there is limited research on uptake especially among medical students. OBJECTIVE: This paper explores the uptake of one such tool, Up-To-Date, when provided free of cost at a medical school in Africa. METHODS: In partnership with the Better Evidence at Ariadne Labs free access to UpToDate was granted through the MakCHS IP address. On-site librarians facilitated training sessions and spread awareness of the tool. Usage data was aggregated, based on log ins and content views, presented and analyzed using Excel tables and graphs. RESULTS: The data shows evidence of meaningful usage, with 43,043 log ins and 15,591 registrations between August 2019 and August 2020. The most common topics viewed were in obstetrics and gynecology, pediatrics, drug information, and infectious diseases. Access occurred mainly through the mobile phone app. CONCLUSION: Findings show usage by various user categories, but with inconsistent uptake and low usage. Librarians can draw upon these results to encourage institutions to support uptake of point-of-care tools in clinical practice.

COVID-19 Vaccine To Vaccination: Why Leaders Must Invest In Delivery Strategies Now.

Worldwide, leaders are implementing nonpharmaceutical interventions to slow transmission of the novel coronavirus while pursuing vaccines that confer immunity to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. In this article we describe lessons learned from past pandemics and vaccine campaigns about the path to successful vaccine delivery. The historical record suggests that to have a widely immunized population, leaders must invest in evidence-based vaccine delivery strategies that generate demand, allocate and distribute vaccines, and verify coverage. To generate demand, there must be an understanding of the roots of vaccine hesitancy, involvement of trusted sources of authority in advocacy for vaccination, and commitment to longitudinal engagement with communities. To allocate vaccines, qualified organizations and expert coalitions must be allowed to determine evidence-based vaccination approaches and generate the political will to ensure the cooperation of local and national governments. To distribute vaccines, the people and organizations with expertise in manufacturing, supply chains, and last-mile distribution must be positioned to direct efforts. To verify vaccine coverage, vaccination tracking systems that are portable, interoperable, and secure must be identified. Lessons of past pandemics suggest that nations should invest in evidence-informed strategies to ensure that coronavirus disease 2019 (COVID-19) vaccines protect individuals, suppress transmission, and minimize disruption to health services and livelihoods.

A Randomized, Double-Blind, Efficacy and Safety Study of PF-05280586 (a Rituximab Biosimilar) Compared with Rituximab Reference Product (MabThera®) in Subjects with Previously Untreated CD20-Positive, Low-Tumor-Burden Follicular Lymphoma (LTB-FL).

BACKGROUND: Biosimilars are highly similar to the licensed biologic ("reference product"), with no clinically meaningful differences in safety, purity, or potency between the two products. OBJECTIVE: This comparative 52-week clinical study evaluated the efficacy, safety, immunogenicity, pharmacokinetics (PK), and pharmacodynamics (PD) of PF-05280586 (Ruxience™ [a rituximab biosimilar]) versus rituximab reference product sourced from the EU (MabThera®; rituximab-EU). PATIENTS AND METHODS: Subjects with CD20-positive, low-tumor-burden follicular lymphoma (LTB-FL) and an Eastern Cooperative Oncology Group performance status 0-1 were randomized (1:1) to PF-05280586 or rituximab-EU (375 mg/m2 intravenously [once weekly for 4 weeks at days 1, 8, 15, and 22]), stratified using the Follicular Lymphoma International Prognostic Index 2 classification. The primary endpoint was overall response rate (ORR) at week 26 (percentage of subjects achieving complete response [CR] or partial response [PR]). Therapeutic equivalence was concluded if the two-sided 95% confidence interval (CI) for the difference in ORR between groups was within the prespecified margin (± 16%). Secondary endpoints included progression-free survival (PFS), CR rate, safety, immunogenicity, PK, and PD. RESULTS: A total of 394 subjects were randomized: PF-05280586 (n = 196) or rituximab-EU (n = 198). ORR at week 26 was 75.5% (PF-05280586) versus 70.7% (rituximab-EU), for a difference of 4.66%; 95% CI (- 4.16 to 13.47), which was entirely within the prespecified equivalence margin. Rates of CR were 29.3% (PF-05280586) versus 31.0% (rituximab-EU). Estimated 1-year PFS rates were 78.2% (95% CI 70.2-84.2) and 83.0% (95% CI 75.0-88.6) for PF-05280586 and rituximab-EU, respectively. Safety, immunogenicity, and mean serum concentrations were similar between groups. CONCLUSIONS: The efficacy, safety, immunogenicity, PK, and PD of PF-05280586 and rituximab-EU were similar up to week 52 in subjects with previously untreated CD20-positive LTB-FL. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02213263 and EudraCT (2014-000132-41).

Better evidence: prospective cohort study assessing the utility of an evidence-based clinical resource at the University of Rwanda.

OBJECTIVE: Evidence-based clinical resources (EBCRs) have the potential to improve diagnostic and therapeutic accuracy. The majority of US teaching medical institutions have incorporated them into clinical training. Many EBCRs are subscription based, and their cost is prohibitive for most clinicians and trainees in low-income and middle-income countries. We sought to determine the utility of EBCRs in an East African medical school. SETTING: The University of Rwanda (UR), a medical school located in East Africa. PARTICIPANTS: Medical students and faculty members at UR. INTERVENTIONS: We offered medical students and faculty at UR free access to UpToDate, a leading EBCR and conducted a cohort study to assess its uptake and usage. Students completed two surveys on their study habits and gave us permission to access their activity on UpToDate and their grades. RESULTS: Of the 980 medical students invited to enrol over 2 years, 547 did (56%). Of eligible final year students, 88% enrolled. At baseline, 92% of students reported ownership of an internet-capable device, and the majority indicated using free online resources frequently for medical education. Enrolled final year students viewed, on average, 1.24 topics per day and continued to use UpToDate frequently after graduation from medical school. Graduating class exam performance was better after introduction of UpToDate than in previous years. CONCLUSIONS: Removal of the cost barrier was sufficient to generate high uptake of a leading EBCR by senior medical students and habituate them to continued usage after graduation.

Will bevacizumab biosimilars impact the value of systemic therapy in gynecologic cancers?

OBJECTIVE: Bevacizumab is an important component in the treatment of various cancers, and despite guidelines recommending its use in both ovarian and cervical cancer, patient access to bevacizumab and other angiogenesis inhibitors is limited. Biosimilars are large, structurally complex molecules that are intended to be highly similar to, and treat the same condition(s) as, an existing licensed or approved (reference) biologic, with no clinically meaningful differences in purity, potency and safety. This article summarizes the role of bevacizumab in the treatment paradigm of ovarian and cervical cancer. We also discuss the potential role of biosimilars to bevacizumab, which may offer more affordable options in the future treatment of gynecologic cancers. METHODS: Literature searches of PubMed and ClinicalTrials.gov databases were conducted. Regulatory and individual pharmaceutical company web pages were also reviewed. Search terms included "biosimilar" and "bevacizumab," and these were used to identify information regarding biosimilar development, reporting results of biosimilar studies or biosimilars in development. RESULTS: At present, four bevacizumab biosimilar candidates are undergoing comparative clinical assessment, with the potential to increase access and offer efficiencies across healthcare systems. CONCLUSIONS: It is anticipated that biologics such as bevacizumab will continue to play a key role in the treatment of an array of gynecologic cancers. Biosimilars to bevacizumab are currently in development and have the potential to increase access to medicines in a variety of settings, including gynecologic cancers.

Biosimilars: Extrapolation for oncology.

A biosimilar is a biologic that is highly similar to a licensed biologic (the reference product) in terms of purity, safety and efficacy. If the reference product is licensed to treat multiple therapeutic indications, extrapolation of indications, i.e., approval of a biosimilar for use in an indication held by the reference product but not directly studied in a comparative clinical trial with the biosimilar, may be possible but has to be scientifically justified. Here, we describe the data required to establish biosimilarity and emphasize that indication extrapolation is based on scientific principles and known mechanism of action.

A clinician's guide to biosimilars in oncology.

Biological agents or "biologics" are widely used in oncology practice for cancer treatment and for the supportive management of treatment-related side effects. Unlike small-molecule generic drugs, exact copies of biologics are impossible to produce because these are large and highly complex molecules produced in living cells. The term "biosimilar" refers to a biological product that is highly similar to a licensed biological product (reference or originator product) with no clinically meaningful differences in terms of safety, purity, or potency. Biosimilars have the potential to provide savings to healthcare systems and to make important biological therapies widely accessible to a global population. As biosimilars for rituximab, trastuzumab, and bevacizumab are expected to reach the market in the near future, clinicians will soon be faced with decisions to consider biosimilars as alternatives to existing reference products. The aim of this article is to inform oncology practitioners about the biosimilar development and evaluation process, and to offer guidance on how to evaluate biosimilar data in order to make informed decisions when integrating these drugs into oncology practice. We will also review several biosimilars that are currently in development for cancer treatment.