title: A framework for Go/No-Go decisions in high-tech R&D

authors: Woollaston, Owen

abstract: New product development (NPD) failure rates range from 40% (Cooper, 2019) to 90% (Kim et al., 2016), so firms must allocate resources effectively, including abandoning failing projects if necessary. However, when to abandon is often unclear, so portfolio managers risk commitment escalation (Eliens et al., 2018) and overinvesting. This study explored the research question: How should firms evaluate whether to continue or abandon projects in high-tech R&D? A dual approach was taken: First, to gain foundational insights, an innovative AI-assisted literature review method was developed and used to create a novel R&D decision-making framework. Second, to test the key concepts of the framework and illustrate its application, an agent-based simulation (Sulis & Taveter, 2022) compared the performance of the framework against risk-based and ROI-based approaches in a 1000-project portfolio. The framework outperformed the other strategies in simulations and emphasised the importance of gatekeeper independence, negotiating clear criteria up front and using formal decision gates. The simulation results also suggested actionable guidance for practitioners: For a feasibility phase to add value, it should cost less than 30% of the project budget and significantly improve cost estimates.
Theoretical contribution: This study integrated key NPD decision theories from real options, behavioural decision-making, and portfolio management and developed a novel decision-making framework while exemplifying the use of AI to enable rapid, scalable research. It then demonstrated that decision gates outperform ROI- and risk-based approaches in simulation.
Practical contribution: For R&D portfolio managers, the study provides a structured decision-making approach and guidance for sizing feasibility studies. For researchers, it provides a methodology for accelerating and scaling literature reviews.

text: A framework for Go/No-Go decisions in high-tech R&D New product development (NPD) failure rates range from 40% (Cooper, 2019) to 90% (Kim et al., 2016), so firms must allocate resources effectively, including abandoning failing projects if necessary. However, when to abandon is often unclear, so portfolio managers risk commitment escalation (Eliens et al., 2018) and overinvesting. This study explored the research question: How should firms evaluate whether to continue or abandon projects in high-tech R&D? A dual approach was taken: First, to gain foundational insights, an innovative AI-assisted literature review method was developed and used to create a novel R&D decision-making framework. Second, to test the key concepts of the framework and illustrate its application, an agent-based simulation (Sulis & Taveter, 2022) compared the performance of the framework against risk-based and ROI-based approaches in a 1000-project portfolio. The framework outperformed the other strategies in simulations and emphasised the importance of gatekeeper independence, negotiating clear criteria up front and using formal decision gates. The simulation results also suggested actionable guidance for practitioners: For a feasibility phase to add value, it should cost less than 30% of the project budget and significantly improve cost estimates.
Theoretical contribution: This study integrated key NPD decision theories from real options, behavioural decision-making, and portfolio management and developed a novel decision-making framework while exemplifying the use of AI to enable rapid, scalable research. It then demonstrated that decision gates outperform ROI- and risk-based approaches in simulation.
Practical contribution: For R&D portfolio managers, the study provides a structured decision-making approach and guidance for sizing feasibility studies. For researchers, it provides a methodology for accelerating and scaling literature reviews.

year: 2024

title: Development of a qPCR method to measure mitochondrial and genomic DNA damage with application to chemotherapy-induced DNA damage and cryopreserved cells

authors: Evans, Stephen Owen

subjects: LORD-Q

abstract: DNA damage quantitation assays such as the comet assay have focused on the measurement of total nuclear damage per cell. The adoption of PCR-based techniques to quantify DNA damage has enabled sequence- and organelle-specific assessment of DNA lesions. Here we report on an adaptation of a qPCR technique to assess DNA damage in nuclear and mitochondrial targets relative to control. Novel aspects of this assay include application of the assay to the Rotor-Gene platform with optimized DNA polymerase/fluorophore/primer set combination in a touchdown PCR protocol. Assay validation was performed using ultraviolet C radiation in A549 and THP1 cancer cell lines. A comparison was made to the comet assay applied to peripheral blood mononuclear cells, and an estimation of the effects of cryopreservation on ultraviolet C-induced DNA damage was carried out. Finally, dose responses for DNA damage were measured in peripheral blood mononuclear cells following exposure to the cytotoxic agents bleomycin and cisplatin. We show reproducible experimental outputs across the tested conditions and concordance with published findings with respect to mitochondrial and nuclear genotoxic susceptibilities. The application of this DNA damage assay to a wide range of clinical and laboratory-derived samples is both feasible and resource-efficient.

text: Development of a qPCR method to measure mitochondrial and genomic DNA damage with application to chemotherapy-induced DNA damage and cryopreserved cells DNA damage quantitation assays such as the comet assay have focused on the measurement of total nuclear damage per cell. The adoption of PCR-based techniques to quantify DNA damage has enabled sequence- and organelle-specific assessment of DNA lesions. Here we report on an adaptation of a qPCR technique to assess DNA damage in nuclear and mitochondrial targets relative to control. Novel aspects of this assay include application of the assay to the Rotor-Gene platform with optimized DNA polymerase/fluorophore/primer set combination in a touchdown PCR protocol. Assay validation was performed using ultraviolet C radiation in A549 and THP1 cancer cell lines. A comparison was made to the comet assay applied to peripheral blood mononuclear cells, and an estimation of the effects of cryopreservation on ultraviolet C-induced DNA damage was carried out. Finally, dose responses for DNA damage were measured in peripheral blood mononuclear cells following exposure to the cytotoxic agents bleomycin and cisplatin. We show reproducible experimental outputs across the tested conditions and concordance with published findings with respect to mitochondrial and nuclear genotoxic susceptibilities. The application of this DNA damage assay to a wide range of clinical and laboratory-derived samples is both feasible and resource-efficient.

year: 2016

title: ‘Pakeha Bill’: William John McClear, a Pakeha who lived at Te Aroha

authors: Hart, Philip

abstract: Born in Ireland to a Scottish soldier named McAleer, McClear, as he would re-name himself, was uncertain of his age, his birthplace, and the spelling of his name – for, like his parents, he was illiterate. After his drunken father, who abandoned his wife and family, sold him to unknown Maori at an unknown date, he was educated in a Maori school and was unable to speak English until the early 1870s, when he was living with Ngati Rahiri at Omahu pa, at Te Aroha. When Pakeha visitors first met him in 1877, he was a popular resident there and known as Pakeha Bill (or Pakeha William).
Possiby involved in mining before the Te Aroha rush, he both invested in and mined in several claims there from 1880 onwards, and at the end of that decade was one of a small group of Waiorongomai miners who took up a claim at Thames. When not mining, he took whatever jobs were available, struggling financially, in part because of a fondness for drink. As, unlike other Pakeha Maori, there was no evidence of his forming a close relationship with any Maori women, he did not benefit from a Maori wife’s landholdings, and he died in poverty.

text: ‘Pakeha Bill’: William John McClear, a Pakeha who lived at Te Aroha Born in Ireland to a Scottish soldier named McAleer, McClear, as he would re-name himself, was uncertain of his age, his birthplace, and the spelling of his name – for, like his parents, he was illiterate. After his drunken father, who abandoned his wife and family, sold him to unknown Maori at an unknown date, he was educated in a Maori school and was unable to speak English until the early 1870s, when he was living with Ngati Rahiri at Omahu pa, at Te Aroha. When Pakeha visitors first met him in 1877, he was a popular resident there and known as Pakeha Bill (or Pakeha William).
Possiby involved in mining before the Te Aroha rush, he both invested in and mined in several claims there from 1880 onwards, and at the end of that decade was one of a small group of Waiorongomai miners who took up a claim at Thames. When not mining, he took whatever jobs were available, struggling financially, in part because of a fondness for drink. As, unlike other Pakeha Maori, there was no evidence of his forming a close relationship with any Maori women, he did not benefit from a Maori wife’s landholdings, and he died in poverty.

year: 2016