Benefit/Risk Assessment Clause Samples
The Benefit/Risk Assessment clause defines the process by which the potential advantages and disadvantages of a particular action, product, or service are evaluated. In practice, this clause typically requires parties to systematically consider both the positive outcomes (such as increased efficiency or profit) and the potential risks (such as financial loss or safety concerns) before proceeding. Its core function is to ensure that decisions are made with a clear understanding of both the benefits and the risks involved, thereby promoting informed decision-making and helping to allocate responsibility for potential negative outcomes.
Benefit/Risk Assessment. Blockade of XPO1 has shown anti-SARS-CoV2 activity in vitro and anti-viral effects in animal models as well as in influenza models. Severe influenza is associated with a pro-inflammatory cytokine profile similar to severe COVID-19. Based on preclinical studies, inhibition of XPO1 is anticipated to confer both anti-SARS-CoV2 and anti-inflammatory activity at relatively low doses of selinexor to be used in this study. Higher doses of selinexor (160 mg per week) approved for use in the treatment of advanced RRMM are associated with dose-dependent and generally reversible nausea, fatigue, emesis, anorexia, low sodium and thrombocytopenia. The lower doses of selinexor used here (60 mg per week) are expected to achieve the relevant pharmacological concentrations. There are no known clinically significant drug-drug interactions with selinexor. The protocol allows concurrent use of other investigational anti-viral and/or anti-inflammatory agents. The highly selective and potent oral XPO1 inhibitors verdinexor and selinexor have no pharmacologically important discernable differences. XPO1 inhibitors have activity in models of sepsis/ARDS, inflammation, and influenza. In a recent study selinexor demonstrated potent activity against SARS-CoV2 (IC50= ~10 nM). The adverse event profile of low dose selinexor consists of low grade, reversible and treatable symptoms (Appendix 2). Therefore, we believe that the opportunity to confer both anti-viral and anti-inflammatory activity with a novel agent targeting a host protein warrants provides a positive risk /benefit assessment in the treatment of severe COVID-19.
Benefit/Risk Assessment. More detailed information about the known and potential benefits and potential risks of RIST4721 may be found in the IB.
Benefit/Risk Assessment. Broad antitumor activity has been observed with selinexor treatment in preclinical and clinical studies. The information about selinexor’s mechanism of action and its efficacy observed in the KCP-330-027 study (NCT04256707) in patients with advanced or metastatic colorectal cancer (CRC), indicates that selinexor 80 mg once weekly with pembrolizumab 400 mg IV once every six weeks has activity in RAS mutated CRC; however, further investigation is warranted to elucidate clinical benefit. Adverse events in the study were consistent with those reported previously for selinexor and pembrolizumab administered separately with no clear overlapping toxicities. AEs noted during the trial include hematological, fatigue, nausea/diarrhea, low sodium/potassium attributed as possible/definite to either selinexor or pembrolizumab or possible with both treatments. In addition, selinexor is currently being evaluated in combination with other agents (targeted therapies and chemo-/radiotherapy). As these clinical trials proceed, more data will become available to assess both the added efficacy and possible adverse events resulting from these combinations to better inform potential trials combining selinexor with immune checkpoint blockade. In ongoing clinical studies, the most common non-hematologic AEs reported as related to selinexor have been predominantly nausea, vomiting, diarrhea, fatigue, anorexia and weight loss, and these AEs were assessed as low-grade and manageable with dose modification or supportive care. Hyponatremia (typically asymptomatic), confused state and dizziness have also been reported. On the other hand, hematological AEs including thrombocytopenia, neutropenia and anemia, which can be higher grade, were reported primarily in patients with hematologic malignancies. Any potential overlapping toxicity, such as thrombocytopenia, will be monitored closely by careful physical examination and clinical laboratory testing on Day 1 and Day 15 of Cycle 1 and Cycle 2 with dose adjustments as per prespecified dose modifications (see Table 4). A summary of the clinical trials, antitumor responses observed, and anticipated adverse events (AEs) of selinexor are found in the Investigator’s Brochure. Pembrolizumab is approved for use in the treatment of patients with unresectable or metastatic MSI-H or dMMR CRC that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan as a result of an accelerated approval based upon the tumor response...
Benefit/Risk Assessment. Detailed information about the known and expected benefits, risks, and reasonably expected adverse events (AEs) of ALXN1840 may be found in the IB. Information about the known or potential risks and benefits are detailed in the sections following. Dose-dependent elevations in transaminases (ALT and AST) Generally mild to moderate in severity, asymptomatic and reversible with dose adjustments were reported, usually after 3-6 weeks of treatment. Results obtained from studies of ALXN1840 and ammonium tetrathiomolybdate in patients with WD; see the IB Regular monitoring of liver function tests. Dose modification or discontinuation (Section 6.6) Anemia Anemia has been observed in patients with WD, attributed to overtreatment and resultant Cu depletion, see the IB Monitoring complete blood count. Dose modification or discontinuation (Section 6.6) Low white blood cell count (leukopenia, bone marrow toxicity) Leukopenia and bone marrow toxicity (myelosuppression) have been observed in patients with WD, attributed to overtreatment and resultant Cu depletion. Results obtained from studies of ALXN1840 and ammonium tetrathiomolybdate in patients with WD; see the IB Monitoring of complete blood count. Dose modification or discontinuation (Section 6.6) Neurological dysfunction Neurological worsening may occur due to Cu mobilization. Peripheral neuropathy may be seen with over-decoppering; however, symptoms such as myelosuppression is typically seen earlier Neurologic dysfunction is not anticipated in HV population. Risks associated with the study design and procedures Participants will undergo repeated blood draws to measure the PK of the study intervention and metabolism. Blood draws may result in ecchymosis, redness and minor pain to the site. On rare occasion, infection or thrombophlebitis can occur Blood draws are optimized for PK. A cannula may be placed to minimize needle sticks; however, a catheter may not be left in place for longer than 72 hours, and should be flushed a minimum of every 8 hours Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; Cu = copper; IB = Investigator’s Brochure; PK = pharmacokinetics; WD = ▇▇▇▇▇▇ Disease.