Expediting treatments in the 21st century: orphan drugs and accelerated approvals.

Background: In response to activated patient communities' catalyzation, two significant efforts by the FDA to expedite treatments have now been in place for multiple decades. In 1983, the United States Congress passed the Orphan Drug Act to provide financial incentives for development of drugs for rare diseases. In 1992, partly in response to the HIV epidemic, the FDA implemented Accelerated Approval (AA) to expedite access to promising new therapies to treat serious conditions with unmet medical need based on surrogate marker efficacy while additional clinical data is confirmed.

MIT CAACB Risk Assessment Case Study: Assessing Virus Cross-Contamination Risk between Two Simultaneous Processes in an Open Biomanufacturing Facility.

Some members of MIT's Consortium on Adventitious Agent Contamination in Biomanufacturing (CAACB) previously published content on the "Quality Risk Management in the Context of Viral Contamination", which described tools, procedures, and methodologies for assessing and managing the risk of a potential virus contamination in cell culture processes. To address the growing industry interest in moving manufacturing toward open ballrooms with functionally closed systems and to demonstrate how the ideas of risk management can be leveraged to perform a risk assessment, CAACB conducted a case study exercise of these new manufacturing modalities. In the case study exercise, a cross-functional team composed of personnel from many of CAACB's industry membership collaboratively assessed the risks of viral cross-contamination between a human and non-human host cell system in an open manufacturing facility.

Patient-Centered Approach to Benefit-Risk Characterization Using Number Needed to Benefit and Number Needed to Harm: Advanced Non-Small-Cell Lung Cancer.

This work summarizes the benefit and risk of the results of clinical trials submitted to the US Food and Drug Administration of therapies for the treatment of non-small cell lung cancer (NSCLC) using number needed to benefit (NNB) and number needed to harm (NNH) metrics. NNB and NNH metrics have been reported as potentially being more patient centric and more intuitive to medical practitioners than more common metrics, such as the hazard ratio, and valuable to medical practitioners in complementing other metrics, such as the median time to event. This approach involved the characterization of efficacy and safety results in terms of NNB and NNH of 30 clinical trials in advanced NSCLC supporting US Food and Drug Administration approval decisions from 2003 to 2017.

Using a Benefit-Risk Analysis Approach to Capture Regulatory Decision Making: Renal Cell Carcinoma.

Drug regulators such as the US Food and Drug Administration (FDA) make decisions about drug approvals based on benefit-risk analysis. In this work, a quantitative benefit-risk analysis approach captures regulatory decision making about new drugs to treat renal cell carcinoma (RCC). Fifteen FDA decisions on RCC drugs based on clinical trials whose results were published from 2005 to 2018 were identified and analyzed.

Using a Benefit-Risk Analysis Approach to Capture Regulatory Decision Making: Melanoma.

Drug regulators seek to make decisions regarding drug approvals based on analysis of the relevant benefits and risks. In this work, 25 US Food and Drug Administration (FDA) decisions on melanoma drugs were identified and analyzed based on clinical trial results published between 1999 and 2017. In each case, the benefits and risks of the new drug in each clinical trial relative to a comparator (typically the control arm of the same clinical trial) were quantified.