Standard of care, institutional obligations, and distributive justice.

The problem of standard of care in clinical research concerns the level of treatment that investigators must provide to subjects in clinical trials. Commentators often formulate answers to this problem by appealing to two distinct types of obligations: professional obligations and natural duties. In this article, I investigate whether investigators also possess institutional obligations that are directly relevant to the problem of standard of care, that is, those obligations a person has because she occupies a particular institutional role. I examine two types of institutional contexts: (1) public research agencies - agencies or departments of states that fund or conduct clinical research in the public interest; and (2) private-for-profit corporations. I argue that investigators who are employed or have their research sponsored by the former have a distinctive institutional obligation to conduct their research in a way that is consistent with the state's duty of distributive justice to provide its citizens with access to basic health care, and its duty to aid citizens of lower income countries. By contrast, I argue that investigators who are employed or have their research sponsored by private-for-profit corporations do not possess this obligation nor any other institutional obligation that is directly relevant to the ethics of RCTs. My account of the institutional obligations of investigators aims to contribute to the development of a reasonable, distributive justice-based account of standard of care.

Policosanol safely down-regulates HMG-CoA reductase - potential as a component of the Esselstyn regimen.

Many of the wide-ranging health benefits conferred by statin therapy are mediated, not by reductions in LDL cholesterol, but rather by inhibition of isoprenylation reactions essential to the activation of Rho family GTPases; this may be the mechanism primarily responsible for the favorable impact of statins on risk for ischemic stroke, senile dementia, and fractures, as well as the anti-hypertensive and platelet-stabilizing actions of these drugs. Indeed, the extent of these benefits is such as to suggest that most adults would be wise to take statins; however, owing to the significant expense of statin therapy, as well as to the potential for dangerous side effects that mandates regular physician follow-up, this strategy appears impractical. However, policosanol, a mixture of long-chain aliphatic alcohols extractable from sugar cane wax, has shown cholesterol-lowering potency comparable to that of statins, and yet appears to be devoid of toxic risk. Recent evidence indicates that policosanol down-regulates cellular expression of HMG-CoA reductase, and thus has the potential to suppress isoprenylation reactions much like statins do. Consistent with this possibility, the results of certain clinical and animal studies demonstrate that policosanol has many effects analogous to those of statins that are not likely explained by reductions of LDL cholesterol. However, unlike statins, policosanol does not directly inhibit HMG-CoA reductase, and even in high concentrations it fails to down-regulate this enzyme by more than 50% - thus likely accounting for the safety of this nutraceutical. In light of the fact that policosanol is quite inexpensive and is becoming available as a non-prescription dietary supplement, it may represent a practical resource that could enable the general public to enjoy health benefits comparable to those conferred by statins. In a long-term clinical study enrolling patients with significant symptomatic coronary disease, Esselstyn has demonstrated that a low-fat, whole-food vegan diet, coupled with sufficient statin therapy to maintain serum cholesterol below 150 mg/dL, can stop the progression of coronary disease and virtually eliminate further risk for heart attack. A comparable regimen, in which policosanol is used in place of statins, may represent a practical strategy whereby nearly everyone willing to commit to health-protective eating can either prevent coronary disease, or prevent pre-existing coronary disease from progressing to a life-threatening event.

Cost effects of surfactant therapy for neonatal respiratory distress syndrome.

OBJECTIVE: To examine the cost effects of a single dose (5 ml/kg) of a protein-free synthetic surfactant (Exosurf) as therapy for neonatal respiratory distress syndrome, for both rescue and prophylactic therapy. RESEARCH DESIGN: Nonblinded, randomized clinical trials of both rescue and prophylactic therapy. Regression analyses were used to control for the independent effects of sex, multiple birth, delivery method, birth weight, and surfactant therapy. SETTING: The prophylactic trial was conducted at a university medical center only; the rescue trial also included a tertiary community hospital. PATIENTS: Prophylaxis was administered immediately after birth to 36 infants (38 control subjects) with birth weights between 700 and 1350 gm. Rescue therapy was administered at 4 to 24 hours of age to 53 infants (51 control subjects) with established respiratory distress syndrome and birth weights > or = 650 gm (no upper limit). Infants in the prophylactic trial were not eligible for the rescue trial. RESULTS: For the rescue trial, there was a $16,600 reduction in average hospital costs (p = 0.18), which was larger than the cost of the surfactant ($450 to $900), yielding a probable net savings. For the prophylactic trial, hospital costs were larger for treated infants versus control subjects who weighed less than about 1100 gm at birth and lower for treated infants versus control subjects who weighed more than 1100 gm at birth (p < 0.05). For the prophylactic sample, the result was an average cost per life saved of $71,500. CONCLUSIONS: Single-dose rescue surfactant therapy is probably a cost-effective therapy because it produced a lower mortality rate for the same (and probably lower) expenditure. Single-dose prophylactic therapy for smaller infants (< or = 1350 gm) appeared to yield a reduction in mortality rate for a small additional cost. The use of multiple-dose therapy in infants who do not respond to initial therapy may alter the effects described above to either increase or decrease the observed cost-effectiveness of surfactant therapy. Regardless, surfactant therapy will remain a cost-effective method of reducing mortality rates, relative to other commonly used health care interventions.

Surfactant replacement therapy in neonates less than 32 weeks gestation: effect on neonatal intensive care resource utilization.

The effect of synthetic surfactant (Exosurf) replacement on complications from hyaline membrane disease (HMD) in infants < 32 weeks gestation and their resource utilization within a neonatal intensive care unit was studied in 1991-92. A control group was selected from infants admitted to the same unit during the preceding 3 years when Exosurf was not available. The infants were controlled for gestation, weight and severity of HMD. Infants given Exosurf had a significant reduction in the incidence of pulmonary interstitial emphysema (PIE), and a marginal decrease in the incidence of pneumothorax. They required fewer days on the ventilator and consumed less of the scarce financial resources. There was no difference in the mortality rate among the two groups. The changes seen were more evident among those infants between 30 and 31 weeks gestation, compared to those < 28 weeks.