Srinivas Teppala

Introduction: Pembrolizumab monotherapy improves survival in advanced non-small cell lung cancer (NSCLC) with programmed death ligand 1 (PD-L1) tumour proportion score (TPS) ≥ 50%. However, survival in randomised trials may not fully reflect outcomes in routine practice, with implications for economic evaluation. Aim: To evaluate the cost-effectiveness of pembrolizumab monotherapy compared with platinum-based chemotherapy from an Australian health-payer perspective, integrating both randomised controlled trial (RCT) and real-world evidence (RWE). Method: A semi-Markov model with three health states (progression-free, progressed disease, death) was developed over a 3-year horizon. Clinical inputs were derived from KEYNOTE-024 for the RCT scenario and from nationwide Australian real-world data for the RWE scenario, with chemotherapy outcomes retained from the pivotal trials in both scenarios. Direct medical costs (2024 AU$) and quality-adjusted life years (QALYs) were estimated. Incremental cost-effectiveness ratios (ICERs) were calculated, probabilistic and deterministic sensitivity analyses conducted. Results: Compared with chemotherapy, pembrolizumab monotherapy was associated with incremental costs of AU$87,399 (RCT-based) and AU$75,935 (RWE-based), and incremental QALY gains of 0.23 and 0.11, respectively. Corresponding ICERs were AU$385,561/QALY (RCT) and AU$705,729/QALY (RWE). At a AU$75,000/QALY willingness-to-pay (WTP) threshold, the probability of cost-effectiveness was < 1% in both scenarios. Differences in overall survival between trial and real-world cohorts likely contributed to the variation in ICERs. Conclusion: At current pricing and Australian WTP thresholds, pembrolizumab monotherapy is unlikely to be cost-effective, with RWE-informed scenarios yielding less favourable cost-effectiveness estimates than from trial data. These findings highlight that cost-effectiveness estimates may be sensitive to differences between trial-based and real-world effectiveness inputs.

1. Lung cancer remains the leading cause of cancer-related mortality worldwide1,2, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of all cases3. A large proportion of pati...

The purpose of this study was to estimate the consensus of Australian Health Professionals and/or Researchers (HP/Rs) and Consumers (patients/family/carers) (Cs) on international genetic testing recommendations. Modified Delphi Panel study with seven domains of interest. Fifty-five statements were devised for an online survey administered in REDCap. HP/Rs and Cs were recruited from professional networks and associations for participation in the study. Statements were rated using a Likert scale and analysed using descriptive statistics. Free text comments were allowed within each domain and analysed using thematic analysis. Thirty-six HP/Rs and 27 Cs participated. There was consensus on testing men with a family history of a high-risk hereditary gene; men with PCa and a family history of Hereditary Breast and Ovarian Cancer (HBOC) syndrome or Lynch syndrome; and men with metastatic PCa. There was consensus on testing BRCA2, BRCA1 and DNA MMR genes for men with metastatic PCa. Thematic analysis of HP/R comments revealed three main topics: the lack of information to make a decision, insufficient knowledge of genetic testing, and capacity to provide genetic testing and counselling. This is the first Australian study on genetic testing recommendations in PCa to inform who should be tested and how. Our study showed apparent deficits in knowledge and implementation, exacerbated by workforce issues around the provision of genetic counselling and testing. Future work should focus on evaluating these recommendations for implementation in Australian practice.

Background People living in regional Queensland, Australia, have less access to health care than their metropolitan neighbours; a gap that is wider if they are also of Aboriginal and Torres Strait Islander ethnicity. The Bariatric Surgery Initiative (BSI) aims to provide metabolic bariatric surgery as a public service accessible to all Queenslanders for patients with morbid obesity according to need, regardless of location or ethnicity. Methods We investigated the BSI’s progress in closing the metro-regional gap by comparing the distribution of referrals for surgery with the geographic and ethnic spread of obesity across Queensland in 2017–2019. Results Regional Queensland is home to 59.8% of Queensland’s individuals with obesity, whereas 40.2% live in metropolitan Brisbane. In contrast, 47.8% of referrals were from regional areas, with 52.2% received from Brisbane. We found that more patients from metropolitan than regional areas underwent metabolic bariatric surgery, probably due to a paucity of referrals from regional locations. Aboriginal and Torres Strait Islander peoples were able to access the service and all patients realised significant health benefits after surgery. Conclusions The BSI improved access to this service, and inequities in metro-regional access may depend on patient choice and healthcare provider awareness of the BSI. Trial registration This initiative was a quality improvement study focused on providing access to care rather than a clinical trial; as such it was not registered as a clinical trial.

Background: Olaparib targets the DNA repair pathways and has revolutionized the management of metastatic castration resistant prostate cancer (mCRPC). Treatment with the drug should be guided by genetic testing; however, published economic evaluations did not consider olaparib and genetic testing as codependent technologies. This study aims to assess the cost-effectiveness of BRCA germline testing to inform olaparib treatment in mCRPC. Methods: We conducted a cost-utility analysis of germline BRCA testing-guided olaparib treatment compared to standard care without testing from an Australian health payer perspective. The analysis applied a decision tree to indicate the germline testing or no testing strategy. A Markov multi-state transition approach was used for patients within each strategy. The model had a time horizon of 5 years. Costs and outcomes were discounted at an annual rate of 5 percent. Decision uncertainty was characterized using probabilistic and scenario analyses. Results: Compared to standard care, BRCA testing-guided olaparib treatment was associated with an incremental cost of AU$7,841 and a gain of 0.06 quality-adjusted life-years (QALYs). The incremental cost-effectiveness ratio (ICER) was AU$143,613 per QALY. The probability of BRCA testing-guided treatment being cost effective at a willingness-to-pay threshold of AU$100,000 per QALY was around 2 percent; however, the likelihood for cost-effectiveness increased to 66 percent if the price of olaparib was reduced by 30 percent. Conclusion: This is the first study to evaluate germline genetic testing and olaparib treatment as codependent technologies in mCRPC. Genetic testing-guided olaparib treatment may be cost-effective with significant discounts on olaparib pricing.

Background: Targeted germline testing is recommended for those with or at risk of breast, ovarian and colorectal cancer. The affordability of genetic sequencing has improved over the past decade, therefore the cost-effectiveness of testing for these cancers is worthy of reassessment. Objective: To systematically review economic evaluations on cost-effectiveness of germline testing in breast, ovarian or colorectal cancer. Methods: A search of PubMed and Embase databases for cost-effectiveness studies on germline testing in breast, ovarian or colorectal cancer, published between 1999 to May 2022. Synthesis of methodology, cost-effectiveness, and reporting (CHEERS checklist) was performed. Results: The incremental cost-effectiveness ratios (ICERs; in 2021-adjusted US$) for germline testing vs. the standard care option, in hereditary breast or ovarian cancer (HBOC) across target settings were as follows: 1) population-wide testing: 344-2.5 million/QALY 2) women with high-risk: dominant-78,118/QALY, 8,337-59,708/LYG 3) existing breast or ovarian cancer: 3,012-72,566/QALY, 39,835/LYG 4) metastatic breast cancer: 158,630/QALY. Likewise, ICERs of germline testing for colorectal cancer across settings were: 1) population-wide testing: 132,200/QALY, 1.1 million/LYG 2) people with high-risk: 32,322-76,750/QALY, dominant-353/LYG 3) patients with existing colorectal cancer: dominant – 54,122/QALY, 98,790-6.3 million/LYG. Key areas of underreporting were inclusion of a health economic analysis plan (100% of HBOC and colorectal studies), engagement of patients and stakeholders (95.4% of HBOC, 100% of colorectal studies) and measurement of outcomes (18.2% HBOC, 38.9% of colorectal studies). Conclusion: Germline testing for HBOC was likely to be cost-effective across most settings, except when used as a co-dependent technology with the PARP inhibitor, olaparib in metastatic breast cancer. In colorectal cancer studies, testing was cost-effective in those with high-risk, but inconclusive in other settings. Cost-effectiveness was sensitive to the prevalence of tested variants, cost of testing, uptake and benefits of prophylactic measures. Policy advice on germline testing should emphasize the importance of these factors in their recommendations.

Children with autism spectrum disorder (ASD) commonly present with comorbid language impairment, negatively impacting their learning and participation across settings. Addressing these needs requires a detailed understanding of their communication trajectories. In this study, we used the language environment and analysis (LENA) system to examine possible changes in children's (a) vocalizations and (b) ratio of speech to nonspeech vocalizations over a 10‐month period. Data for 23 children with ASD (17M, 6F; ages 32–67 months) were analyzed, including monthly 3‐hr in‐class recordings and standardized measures of language, cognition, and ASD characteristics. Using hierarchical generalized linear models, we found significant time‐trends for child vocalizations (P ≤ 0.001) and the vocalization ratio (P = 0.02), reflecting a waxing and waning pattern. Children with higher expressive language scores (Mullen scales of early learning, Vineland adaptive behavior scales – 2nd Ed.) and nonverbal cognition (Mullen scales of early learning), and fewer ASD characteristics (social communication questionnaire) demonstrated greater increases in the vocalization ratio over time (P values 0.04–0.01). Children with greater language and cognition difficulties were the most vocal, but produced a higher proportion of nonspeech vocalizations. The results demonstrate that significant fluctuations, as opposed to linear increases, may be observed in children with ASD receiving intervention, highlighting the value of assessment at multiple time‐points. In addition, the findings highlight the need to consider both the quantity (vocalization counts) and quality (ratio of speech to nonspeech vocalizations) when interpreting LENA data, with the latter appearing to provide a more robust measure of communication. Autism Research 2019, 12: 830–842. © 2019 International Society for Autism Research, Wiley Periodicals, Inc.Lay In this study, we examined possible changes in speech and nonspeech vocalizations in 23 children with autism attending a comprehensive early intervention program over a 10‐month period. Contrary to our expectation, we observed a waxing and waning pattern of change in children's vocalizations over time, rather than a steady increase. We also found evidence to suggest that looking at the quality of children's vocalizations (i.e., the ratio of speech to nonspeech vocalizations) provides a more accurate picture of children's development than simply looking at the quantity (i.e., how frequently they vocalize).

There is awareness of likelihood of abnormal spermatozoa in obese men; however, results from previous studies are inconclusive. Advances in computer-aided sperm analysis (CASA) enable precise evaluation of sperm quality and include assessment of several parameters. We studied a retrospective cohort of 1285 men with CASA data from our infertility clinic during 2016. Obesity (BMI ≥30) was associated with lower (mean ± SE) volume (−0.28 ± 0.12, p-value = .04), sperm count (48.36 ± 16.51, p-value = .002), concentration (−15.83 ± 5.40, p-value = .01), progressive motility (−4.45 ± 1.92, p-value = .001), total motility (−5.50 ± 2.12, p-value = .002), average curve velocity (μm/s) (−2.09 ± 0.85, p-value = .001), average path velocity (μm/s) (−1.59 ± 0.75, p-value = .006), and higher per cent head defects (0.92 ± 0.81, p-value = .02), thin heads (1.12 ± 0.39, p-value = .007) and pyriform heads (1.36 ± 0.65, p-value = .02). Obese men were also more likely to have (odds ratio, 95% CI) oligospermia (1.67, 1.15–2.41, p-value = .007) and asthenospermia (1.82, 1.20–2.77, p-value = .005). This is the first report of abnormal sperm parameters in obese men based on CASA. Clinicians may need to factor in paternal obesity prior to assisted reproduction.