The Fragility of Scientific Rigour and Integrity in "Sped up Science": Research Misconduct, Bias, and Hype and in the COVID-19 Pandemic.

During the early years of the COVID-19 pandemic, preclinical and clinical research were sped up and scaled up in both the public and private sectors and in partnerships between them. This resulted in some extraordinary advances, but it also raised a range of issues regarding the ethics, rigour, and integrity of scientific research, academic publication, and public communication. Many of the failures of scientific rigour and integrity that occurred during the pandemic were exacerbated by the rush to generate, disseminate, and implement research findings, which not only created opportunities for unscrupulous actors but also compromised the methodological, peer review, and advisory processes that would usually identify sub-standard research and prevent compromised clinical or policy-level decisions. While it would be tempting to attribute these failures of science and its translation solely to the "unprecedented" circumstances of the COVID-19 pandemic, the reality is that they preceded the pandemic and will continue to arise once it is over. Existing strategies for promoting scientific rigour and integrity need to be made more rigorous, better integrated into research training and institutional cultures, and made more sophisticated. They might also need to be modified or supplemented with other strategies that are fit for purpose not only in public health emergencies but in any research that is sped-up and scaled up to address urgent unmet medical needs.

Dilemmas in the compassionate supply of investigational cancer drugs.

In Australia, patients who want to access medicines that are not yet approved have only two options: to enroll in a clinical trial if they are eligible, or obtain their medicine through 'compassionate supply', which is provided at the discretion of the manufacturer. In this article, we explore ethical issues associated with the provision of oncology medicines that are still in development, either prior to regulatory approval or government reimbursement.

No evidence or no alternative? Taking responsibility for off-label prescribing.

Recombinant activated factor VII (rFVIIa) is registered for patients with rare haematological disorders, but is used 'off-label' in many other situations, including intracranial haemorrhage, cardiac surgery, trauma, transplantation and prostatectomy. Lack of systematic evidence to support these off-label uses has not slowed the growth of off-label prescribing of rFVIIa. We use the case of rFVIIa to illustrate the issues raised by off-label prescribing, and the kind of impasse that can arise when views about evidence, expertise and clinical necessity are in conflict. We argue that clinicians, hospital drug committees and regulators all need to acknowledge the complexity of prescribing decisions, and ensure that decisions to prescribe off-label are sufficiently justified.

Eliciting views of Australian pharmaceutical industry employees on collaboration and the concept of Quality Use of Medicines.

BACKGROUND: Pharmaceutical industry involvement in biomedicine has produced major benefits but has also caused concern. At present, there is no consensus as to how medical and government organizations should relate to the pharmaceutical industry and this is partly due to the absence of systematic study of the various alternatives. In Australia industry cooperation has been elicited through the 'Quality Use of Medicines' (QUM) framework within the 'National Medicines Policy'. Little is known about the way employees of pharmaceutical companies respond to the QUM policy and strategies. AIMS: To examine the engagement of the Australian pharmaceutical industry with QUM with a view to assisting medical, government and consumer organizations who may wish to collaborate with industry. METHODS: We carried out a qualitative study using in-depth, semistructured interviews with industry employees, primarily from medical and regulatory affairs departments. RESULTS: Employees of pharmaceutical companies claim that collaboration is important, and that they are altruistic and committed to QUM. At the same time, there is little evidence from this study to support the notion that QUM has brought about structural changes to industry or is positioned as the central goal or framework in designing a company's operational strategies. Moreover, there is a significant degree of ambivalence towards governments and medical organizations. CONCLUSIONS: Employees within the pharmaceutical industry claim a commitment to collaboration and QUM. While these claims cannot be taken entirely at face value, there is potential for meaningful collaboration with industry.

The strengths and limitations of empirical bioethics.

The past two decades have been witness to an "empirical turn" in bioethics. Whereas once this field of study concerned itself purely with theoretical analysis of ethical issues emerging in the design and delivery of health care, increasingly bioethics has embraced a range of empirical research methods from the social sciences and humanities. The emergence of "empirical bioethics" has, however, been the subject of enormous debate, both in regard to its methods and its purpose. For the most part these criticisms fail to appreciate the assumptions that underpin empirical bioethics or misrepresent the claims that are made about its moral utility. This article provides a brief account of the assumptions, strengths and limitations of empirical bioethics.

Informed consent and medical ordeal: a qualitative study.

BACKGROUND: Informed consent is a mainstay of clinical practice, with both moral and legal forces. Material disclosure about extreme treatments, however, is unlikely to convey the full impact of the experience of treatment. Informed consent may be flawed under such circumstances. The aims of this study were to compare expressed satisfaction with pretreatment information to satisfaction after experiencing autologous stem cell transplantation for recurrent lymphoma. METHODS: A qualitative, narrative-based cohort study was conducted in a bone-marrow transplant unit of a teaching hospital at Westmead Hospital, Sydney, Australia. The cohort consisted of 10 transplant recipients and 9 of their nominated lay carers. The outcome measure was satisfaction expressed in narrative interviews at the time of transplantation and 3 months later. We used discourse-analytic techniques to examine the narratives. RESULTS: Both patients and carers expressed high satisfaction with the information given by individual clinicians and by speakers at a formal Information Day held before transplantation. At the first interview, neither patients nor carers commented much on the forthcoming ordeal of chemotherapy and bone marrow ablation, although all patients had undergone previous chemotherapy. At the second interview, the ordeal dominated the narratives and retrospective dissatisfaction with information was common. CONCLUSION: This study suggests that information about treatment theories and protocols can be satisfactorily communicated, but personal experience of suffering defies communication. This finding has serious implications for the practices involved in obtaining informed consent and for the very notion of informed consent.

Managing scientific uncertainty in health legislation.

Legislation and regulation of biomedical research is seldom a one-off process since biomedical science evolves rapidly, dynamically and often unpredictably. This paper discusses the challenges faced by regulators who need to produce legislation and policy in rapidly changing fields and outlines some practical suggestions for managing law reform and policy-making under these circumstances.

Consent in crisis: the need to reconceptualize consent to tissue banking research.

The issues surrounding consent to tissue banking research in Australia are complex and have created a forum of intense debate, thus providing a window of opportunity to critically appraise and challenge standard models of consent for research in general and for tissue banking research in particular. The usual practical difficulties associated with meeting the criteria for valid consent to research (including adequate information provision and voluntariness) are amplified in the case of tissue banking research. A number of models, based on widely accepted ethical principles, have been proposed to improve the process of obtaining consent to tissue banking research, all of which assume that the consent of individual tissue donors is needed to meet the criteria for valid consent. Feminist and communitarian theories use many of the same criteria for valid consent but interpret these criteria differently and de-emphasize the importance of individual autonomy as the central criterion for valid consent. An enriched model of consent incorporating feminist and communitarian ideas could satisfy the currently accepted criteria for valid consent while also furthering a broader range of community values.