Trends in risks associated with new drug development: success rates for investigational drugs.

This study utilizes both public and private data sources to estimate clinical phase transition and clinical approval probabilities for drugs in the development pipelines of the 50 largest pharmaceutical firms (by sales). The study examined the development histories of these investigational compounds from the time point at which they first entered clinical testing (1993-2004) through June 2009. The clinical approval success rate in the United States was 16% for self-originated drugs (originating from the pharmaceutical company itself) during both the 1993-1998 and the 1999-2004 subperiods. For all compounds (including licensed-in and licensed-out drugs in addition to self-originated drugs), the clinical approval success rate for the entire study period was 19%. The estimated clinical approval success rates and phase transition probabilities differed significantly by therapeutic class. The estimated clinical approval success rate for self-originated compounds over the entire study period was 32% for large molecules and 13% for small molecules. The estimated transition probabilities were also higher for all clinical phases with respect to large molecules.

Enhancement of proxy appointment for older persons: physician counselling in the ambulatory setting.

OBJECTIVE: To determine the effectiveness of physician-initiated counselling on the rate of health care proxy appointment. DESIGN: Observational study of an intervention in a convenience sample. SETTING: A geriatric outpatient clinic in a tertiary care teaching hospital, New York, New York. PARTICIPANTS: A total of 687 patients enrolled in the geriatric clinic during the study period March 1991 through June 1993. INTERVENTION: Physician counselling about the New York State Health Care Proxy Law, distribution of educational materials and healthcare proxy forms, and reminders in 331 of 466 eligible patients. MEASUREMENTS: Rate of healthcare proxy appointment in eligible and counselled groups; predictors of appointment and non-appointment; time elapsed from counselling to appointment; reasons for non-appointment; characteristics of the proxy appointment process. RESULTS: A healthcare proxy was appointed for 31.5% of patients eligible for counselling and for 44% of patients who actually received the intervention, compared with a 2.3% proxy appointment rate at baseline. Eighty-one percent of the patients completing the proxy appointment process did so at or before their third clinic return visit after the counselling intervention. Of the counselled patients who did not appoint a proxy, 25% explicitly declined, and 75% had not come to a decision by the end of the study period. Proxy completion was associated with ethnicity, education, and more frequent clinic visits. Of those who appointed a proxy, 97% had good or fair comprehension of the procedure, 92% discussed the appointment with their designees, 63% appointed a daughter or son, and 80% discussed their wishes for care at the end of life with their proxy. CONCLUSIONS: Physician counselling of older outpatients is an effective means of increasing healthcare proxy appointments.

Substituted judgment: how accurate are proxy predictions?

Substituted judgment has been proposed as a method of promoting the autonomy of the mentally incapacitated patient, but little is known about the accuracy of surrogate decision makers in reflecting the true wishes of patients. In this study, surrogate decision makers' views (those of primary care providers and close family members) were compared with the decisions of currently competent chronically ill elderly patients, using a hypothetic cardiopulmonary resuscitation scenario under circumstances of current health and progressive dementia. Concordance between patients and their surrogates was evaluated by assessing percent agreement, kappa coefficient (for concordance beyond chance), and directionality of discrepant responses. Most patient respondents chose to be resuscitated in both scenarios. Although patients predicted that both their physicians (90%) and family members (87%) would accurately represent their wishes, neither family members nor physicians, in fact, were able to adequately predict patients' wishes in both scenarios (kappa less than or equal to 0.3 in all scenarios; percent agreement range, 59% to 88%). Few patients had ever discussed their resuscitation preferences with either their family member (16%) or their physician (7%). These results cast doubt on the usefulness of a strict substituted judgment standard as an approach to medical decision making for patients with diminished mental capacity.