Preferences for potential benefits and risks for gene therapy in the treatment of sickle cell disease.

Objective of this study is to quantify benefit-risk tradeoffs pertaining to potential gene therapies among adults and parents/caregivers of children with sickle cell disease (SCD). A discrete-choice experiment survey was developed in which respondents selected their preferred treatment alternatives in a series of experimentally controlled pairs of hypothetical gene therapies and a "no gene therapy" option. Gene therapy alternatives were defined based on the chance of eliminating SCD symptoms, expected increases in life expectancy they could offer, treatment-related risk of death, and potential increases in lifetime cancer risk. Respondents made selections based on their current disease severity and in the context of expectations of worsened disease. Three clinical sites and 1 patient organization recruited 174 adult patients and 109 parents of children with SCD to complete the survey. Adult and parent respondents were generally willing to choose gene therapies, but the adults required higher expected levels of efficacy (ie, higher chance of eliminating symptoms) than parents to choose gene therapies that conferred mortality risks of ≥10%. When adults and parents of children with less severe symptoms were asked to consider scenarios of higher levels of disease severity, the increased risk tolerance, and the lowest acceptable level of efficacy for gene therapies with mortality risks dropped by >50%. Baseline SCD symptoms are a major driver of gene therapy acceptability. Adults and parents of patients with milder symptoms may prefer other treatment options; however, an expectation of symptoms deterioration triggers strong reassessment of the acceptable benefit-risk balance of this novel technology.

Incorporating patient-preference evidence into regulatory decision making.

BACKGROUND: Patients have a unique role in deciding what treatments should be available for them and regulatory agencies should take their preferences into account when making treatment approval decisions. This is the first study designed to obtain quantitative patient-preference evidence to inform regulatory approval decisions by the Food and Drug Administration Center for Devices and Radiological Health. METHODS: Five-hundred and forty United States adults with body mass index (BMI) ≥ 30 kg/m(2) evaluated tradeoffs among effectiveness, safety, and other attributes of weight-loss devices in a scientific survey. Discrete-choice experiments were used to quantify the importance of safety, effectiveness, and other attributes of weight-loss devices to obese respondents. A tool based on these measures is being used to inform benefit-risk assessments for premarket approval of medical devices. RESULTS: Respondent choices yielded preference scores indicating their relative value for attributes of weight-loss devices in this study. We developed a tool to estimate the minimum weight loss acceptable by a patient to receive a device with a given risk profile and the maximum mortality risk tolerable in exchange for a given weight loss. For example, to accept a device with 0.01 % mortality risk, a risk tolerant patient will require about 10 % total body weight loss lasting 5 years. CONCLUSIONS: Patient preference evidence was used make regulatory decision making more patient-centered. In addition, we captured the heterogeneity of patient preferences allowing market approval of effective devices for risk tolerant patients. CDRH is using the study tool to define minimum clinical effectiveness to evaluate new weight-loss devices. The methods presented can be applied to a wide variety of medical products. This study supports the ongoing development of a guidance document on incorporating patient preferences into medical-device premarket approval decisions.

Decision analysis of retrievable inferior vena cava filters in patients without pulmonary embolism.

BACKGROUND: Retrievable filters are increasingly implanted for prophylaxis in patients without pulmonary embolism (PE) but who may be at transient risk. These devices are often not removed after the risk of PE has diminished. This study employs decision analysis to weigh the risks and benefits of retrievable filter use as a function of the filter's time in situ. METHODS: Medical literature on patients with inferior vena cava (IVC) filters and a transient risk of PE were reviewed. Weights reflecting relative severity were assigned to each adverse event. The risk score was defined as weight × occurrence rate and combines the frequency and severity for each type of adverse event. The value function in the decision model combines the following risks: (1) risk in situ; (2) risk of removal, and (3) relative risk without filters. A decreasing net risk score represents a net expected benefit, and an increasing net risk score indicates the expected harm outweighs the expected benefit. RESULTS: The net risk score reaches its minimum between day 29 and 54 postimplantation. This is consistent with an increasing net risk associated with continued use of retrievable IVC filters in patients with transient, reversible risk of PE. The results were insensitive to reasonable variations in the assessed weights and adverse event occurrence rates. CONCLUSIONS: For patients with retrievable IVC filters in whom the transient risk of PE has passed, quantitative decision analysis suggests the benefit/risk profile begins to favor filter removal between 29 and 54 days after implantation.