Inference and Decision Making for 21st-Century Drug Development and Approval

ABSTRACT

The cost and time of pharmaceutical drug development continue to grow at rates that many say are unsustainable. These trends have enormous impact on what treatments get to patients, when they get them and how they are used. The statistical framework for supporting decisions in regulated clinical development of new medicines has followed a traditional path of frequentist methodology. Trials using hypothesis tests of “no treatment effect” are done routinely, and the p-value < 0.05 is often the determinant of what constitutes a “successful” trial. Many drugs fail in clinical development, adding to the cost of new medicines, and some evidence points blame at the deficiencies of the frequentist paradigm. An unknown number effective medicines may have been abandoned because trials were declared “unsuccessful” due to a p-value exceeding 0.05. Recently, the Bayesian paradigm has shown utility in the clinical drug development process for its probability-based inference. We argue for a Bayesian approach that employs data from other trials as a “prior” for Phase 3 trials so that synthesized evidence across trials can be utilized to compute probability statements that are valuable for understanding the magnitude of treatment effect. Such a Bayesian paradigm provides a promising framework for improving statistical inference and regulatory decision making.     

Multi-valued strategy-proof social choice rules

In this paper we introduce a new definition of strategy-proofness for multi-valued social choice correspondences. We prove two Gibbard-Satterthwaite type results for strategy-proof social choice correspondences. These results show that allowing multiple outcomes as social choices will not necessarily lead to an escape from the Gibbard-Satterthwaite impossibility theorem. Received: 24 January 2001/Accepted: 19 March 2001     

Dementia Problem Behavior and the Production of Informal Caregiving Services

Informal caregivers of individuals with Alzheimer's disease spend a considerable amount of time providing care. In this paper, we use Grossman's health production and Becker's time allocation models to develop a model of informal care provision to elderly dementia patients. In our model, time inputs produce caregiving services, which provides utility to the caregiver, but reduces leisure. We assume that time is less productive of services on the margin as the disease progresses. In this framework, an increase in patients' disease severity does not necessarily increase informal caregiver time input. The cost of formal care establishes a reservation price for informal caregiving. When the costs of informal caregiving rise above this reservation level, the patient is institutionalized. We test empirically the effect of deterioration in the patients' condition, proxied by both disease severity and dementia problem behavior, on informal caregiving time. We find that dementia-related problem behaviors and functional limitations significantly increase inputs of informal caregiving time. Patients' problem behavior exerts a modifying effect on functional limitations, and patients' comorbidities have no effect on informal caregiving time.     

Generating random variates from D-distributions via substitution sampling

Laud et al. (1993) describe a method for random variate generation from D-distributions. In this paper an alternative method using substitution sampling is given. An algorithm for the random variate generation from SD-distributions is also given.     

THE IMPLICATIONS OF CHOOSING "NO RACE" ON THE SALIENCE OF HISPANIC IDENTITY: How Racial and Ethnic Backgrounds Intersect among Hispanic Adolescents

Using data from the National Longitudinal Study of Adolescent Health (Add Health), a nationally representative sample of youth from 7th to 12th grades, we examined how racial and ethnic identification overlap among Hispanic adolescents. We evaluated the relative proximity between race and ethnic identifiers among Hispanics. Empirical analyses suggest that the racial identification of other students at school has a significant impact on the odds of choosing particular racial identifiers. Both Hispanic and non-Hispanic schoolmates' racial identification is related to the racial identification of Hispanic adolescents. We also find evidence that both ethnicity and race are distinct stratifiers among Hispanics. Overall, our findings support the notion that Hispanic may be a more meaningful "racial" identity than black, white, or other, but we also find that racial identification and ethnic background are still important and meaningful dividers among Hispanic youth.