The Availability of Reporting Channels, Tone at the Top, and Whistleblowing Intentions

SOX requires the establishment of anonymous whistleblowing channels for public companies, but private companies are free to implement the channel(s) of their choosing. Although anonymous channels have long been considered a “best practice”, the evidence on their efficacy is mixed, creating confusion as to how private companies should proceed. Additionally, most studies comparing non-anonymous and anonymous channels have used a within-participants design, where both channels are available, limiting their ability to determine the incremental effectiveness of different whistleblowing systems. We find that offering either an anonymous channel or dual channels improves reporting intentions, relative to a non-anonymous channel, but primarily when tone at the top is weak. When tone at the top is strong, reporting intentions are not statistically different across the three systems. We also find no evidence that dual channels improve whistleblowing intentions relative to an anonymous channel, regardless of the tone at the top.

Implication of backward contact tracing in the presence of overdispersed transmission in COVID-19 outbreaks

Introduction: Contact tracing has the potential to control outbreaks without the need for stringent physical distancing policies, e.g. civil lockdowns. Unlike forward contact tracing, backward contact tracing identifies the source of newly detected cases. This approach is particularly valuable when there is high individual-level variation in the number of secondary transmissions (overdispersion). Methods: By using a simple branching process model, we explored the potential of combining backward contact tracing with more conventional forward contact tracing for control of COVID-19. We estimated the typical size of clusters that can be reached by backward tracing and simulated the incremental effectiveness of combining backward tracing with conventional forward tracing. Results: Across ranges of parameter values consistent with dynamics of SARS-CoV-2, backward tracing is expected to identify a primary case generating 3-10 times more infections than a randomly chosen case, typically increasing the proportion of subsequent cases averted by a factor of 2-3. The estimated number of cases averted by backward tracing became greater with a higher degree of overdispersion. Conclusion: Backward contact tracing can be an effective tool for outbreak control, especially in the presence of overdispersion as is observed with SARS-CoV-2.

Implication of backward contact tracing in the presence of overdispersed transmission in COVID-19 outbreaks

Introduction: Contact tracing has the potential to control outbreaks without the need for stringent physical distancing policies, e.g. civil lockdowns. Unlike forward contact tracing, backward contact tracing identifies the source of newly detected cases. This approach is particularly valuable when there is high individual-level variation in the number of secondary transmissions (overdispersion). Methods: By using a simple branching process model, we explored the potential of combining backward contact tracing with more conventional forward contact tracing for control of COVID-19. We estimated the typical size of clusters that can be reached by backward tracing and simulated the incremental effectiveness of combining backward tracing with conventional forward tracing. Results: Across ranges of parameter values consistent with dynamics of SARS-CoV-2, backward tracing is expected to identify a primary case generating 3-10 times more infections than a randomly chosen case, typically increasing the proportion of subsequent cases averted by a factor of 2-3. The estimated number of cases averted by backward tracing became greater with a higher degree of overdispersion. Conclusion: Backward contact tracing can be an effective tool for outbreak control, especially in the presence of overdispersion as is observed with SARS-CoV-2.

Cost-Effectiveness of Once-Weekly Selinexor, Bortezomib, and Dexamethasone (SVd) Versus Twice-Weekly Bortezomib and Dexamethasone (Vd) in Relapsed or Refractory Multiple Myeloma

Introduction: The phase III BOSTON trial reported that once-weekly therapy with selinexor, bortezomib, and dexamethasone (SVd) significantly prolonged progression-free survival for patients with relapsed or refractory (R/R) multiple myeloma compared to twice-weekly treatment with bortezomib and dexamethasone alone (Vd). Although once-weekly SVd reduces the risk of disease progression as well as the cumulative exposure of patients to bortezomib and dexamethasone, selinexor is a costly drug-priced at nearly $22,000 per month-and is associated with significant toxicity. As a result, it is unclear whether SVd provides sufficient value in this clinical setting. In this study, we assess the cost-effectiveness of once-weekly SVd versus twice-weekly Vd in patients with R/R multiple myeloma. Methods: Our cost-effectiveness analysis was based on a Markov model. Simulated patients mirrored the cohort studied in the BOSTON trial; the median age of the population was 66 years, 57% were male and all had received 1-3 prior lines of therapy. Patients entered the model with R/R myeloma and received treatment with SVd or Vd; upon disease progression, all patients subsequently received identical lines of post-progression therapy. Our base-case model (Figure 1) followed SVd/Vd progression sequentially with daratumumab, carfilzomib, and dexamethasone (DKd), pomalidomide and dexamethasone (Pd), and best supportive care. We derived transition probabilities from large randomized trials using parametric survival modeling. The utility of each health state and the costs of treatment, adverse events, and terminal care were derived from literature and Medicare fee schedules. As data evaluating the quality of life with SVd vs Vd is not yet available, we assumed identical utility values for both treatment regimens. We calculated the incremental cost effectiveness ratio (ICER) from a US payer perspective, using a lifetime horizon, an annual discount rate of 3%, and a willingness-to-pay threshold of $150,000/quality-adjusted life year (QALY). One-way and probabilistic sensitivity analyses were conducted to evaluate uncertainty in our model. Results: In our base-case model, SVd was associated with an improvement of 0.37 QALYs compared to Vd alone (3.43 vs 3.06 QALYs, respectively). However, the incremental lifetime cost of SVd was $177,126 ($1,013,851 vs $836,725, respectively), leading to an ICER of $479,572/QALY. The monthly cost of selinexor would need to be decreased by approximately 51%, from $21,424 to $10,415, in order for SVd to be cost-effective compared to Vd alone in R/R patients. Our model was most sensitive to the hazard ratio of SVd relative to Vd; decreasing the HR from 0.70 to 0.53 decreased the ICER to $285,251/QALY, while increasing the HR to 0.93 increased the ICER to $1,738,546/QALY. Of note, all ICERs during one-way sensitivity analysis and >99% of ICERs during probabilistic sensitivity analysis remained above the willingness-to-pay threshold of $150,000 QALY. We also incorporated two scenario analyses; in the first, patients in the Vd arm received therapy with selinexor and dexamethasone (Sd) after progression from Pd, before receiving best supportive care. In this scenario, SVd was associated with an incremental cost of $112,445 ($1,013,851 vs $901,406), an incremental effectiveness of 0.24 QALYs (3.43 vs 3.19 QALYs), and an ICER of $464,557/QALY. In the second scenario analysis, we assumed that patients had received DKd prior to SVd/Vd; as a result, patients that progressed on SVd or Vd subsequently received Pd followed by best supportive care. Here, SVd was associated with an incremental cost of $222,864 ($418,526 vs $195,662), an incremental effectiveness of 0.49 QALYs (1.90 vs 1.41 QALYs), and an ICER of $456,080/QALY. Conclusions: Use of once-weekly SVd for patients with relapsed or refractory multiple myeloma is unlikely to be cost-effective under current pricing, compared to twice-weekly Vd. The price of selinexor would need to be decreased substantially in order to reduce the ICER of SVd to widely acceptable values. Disclosures Huntington: DTRM: Research Funding; Pharmacyclics: Honoraria; TG Therapeutics: Research Funding; Genentech: Consultancy; Celgene: Consultancy, Research Funding; Bayer: Consultancy, Honoraria; Astrazeneca: Honoraria; AbbVie: Consultancy; Novartis: Consultancy. Giri:Carevive Systems: Research Funding; Carevive Systems: Honoraria; Pack Health: Research Funding.

Implication of backward contact tracing in the presence of overdispersed transmission in COVID-19 outbreaks

Introduction: Contact tracing has the potential to control outbreaks without the need for stringent physical distancing policies, e.g. civil lockdowns. Unlike forward contact tracing, backward contact tracing identifies the source of newly detected cases. This approach is particularly valuable when there is high individual-level variation in the number of secondary transmissions (overdispersion). Methods: By using a simple branching process model, we explored the potential of combining backward contact tracing with more conventional forward contact tracing for control of COVID-19. We estimated the typical size of clusters that can be reached by backward tracing and simulated the incremental effectiveness of combining backward tracing with conventional forward tracing. Results: Across ranges of parameter values consistent with dynamics of SARS-CoV-2, backward tracing is expected to identify a primary case generating 3-10 times more infections than average, typically increasing the proportion of subsequent cases averted by a factor of 2-3. The estimated number of cases averted by backward tracing became greater with a higher degree of overdispersion. Conclusion: Backward contact tracing can be an effective tool for outbreak control, especially in the presence of overdispersion as was observed with SARS-CoV-2.

CAR-T therapy and historical trends in effectiveness and cost–effectiveness of oncology treatments

Aim: This study examines how chimeric antigen receptor T-cell (CAR-T) therapy’s incremental effectiveness and cost–effectiveness profile fits into the recent history of anticancer treatments. Materials & methods: We conducted graphical and multivariable analyses using data from the Cost–Effectiveness Analysis Registry of the Tufts Medical Center and the Institute for Clinical and Economic Review’s analysis of CAR-T therapies. We collected additional information including the US FDA approval years for pharmacologic innovations. Results: CAR-T provided 5.03 (95% CI: 3.88–6.18) more incremental quality-adjusted life-years than the average pharmaceutical intervention and 4.61 (95% CI: 1.67–7.56) more than the average nonpharmaceutical intervention, while retaining similar cost–effectiveness. There was evidence of worsening cost–effectiveness by approval year for pharmaceutical interventions. Limitations: Analysis is limited to anticancer treatments studied in cost–utility analyses, estimated to cover approximately 60% of FDA-approved antineoplastic agents. Conclusion: CAR-T therapy breaks a pattern of stagnant efficacy growth in pharmaceutical innovation and demonstrates significantly greater incremental effectiveness and similar cost–effectiveness to prior innovations.