History of Orphan Drug Regulation-United States and Beyond.

The US Orphan Drug Act, passed in 1982, was the first orphan drug legislation in the world. It is a law based on economic incentives making it financially possible for pharmaceutical firms to develop products for small patient populations. Since passage, many additional countries have developed orphan drug programs and many pharmaceutical firms have developed around the orphan program. Today, more than 500 drugs for rare diseases have been developed in the United States.

Orphan drug product regulation--United States.

The legislative history of the United States Orphan Drug Act began with rare, unanimous approval by the United States Congress. The Act, mid consequently the Regulations, have evolved since then. The two-stage process of Orphan Drug designation and approval is outlined, as well as the incentives that are offered to commercial companies for their implementation. Orphan Drugs are likely to be over-represented among drugs used under "Treatment" INDs. For patent- and "drug-difference" reasons, the benefits under the Orphan Drug Act are especially valuable to those who develop biologics. By any measure, this legislation, which requires only voluntary participation, has been a success; because the human genome is likely to lead to more biologicals than orthodox drugs, this success is likely to continue into the future. But even so, the 18-year experience with Orphan Drugs in the United States has led to some 225 Orphan Product approvals that benefit many millions of patients.

School-based methylphenidate placebo protocols: methodological and practical issues.

Around 1990, psychologists and educators began to notice increasing use of methylphenidate by students. Diagnosis of attention-deficit/hyperactivity disorder by family physicians and pediatricians was most commonly based on brief behavioral descriptions by parents and, infrequently, by use of rating scales. At that time, the present researchers began to explore the development of a school-based, methodologically sound, and inexpensive method of assessing the efficacy of stimulant medications, which would ensure reasonable compliance by teachers, parents, and students in monitoring the effects of medications and placebos. This article focuses on the methodological issues involved in choosing instruments to monitor behavior, once a comprehensive evaluation has suggested trials on Ritalin. Case examples illustrate problems of teacher compliance in filling out measures, supplying adequate placebos, and obtaining physician cooperation, and with the practical issue of providing adequate data without overwhelming the time and resources of participants. Emerging school-based methodologies are discussed with recommendations for future efforts.

Evaluation of orphan products by the U.S. Food and Drug Administration.

Orphan drug products generally are used in treating or preventing rare diseases. The small number of patients available for study may create special problems in the evaluation of these products. This paper examines some of the special problems that are associated with the design and implementation of studies to evaluate the safety and efficacy of orphan drugs. The U.S. Food and Drug Administration (FDA) has not established special criteria for evaluating orphan drugs per se, but the FDA has been flexible in evaluating drug products that present special problems, especially when these products are for treatment of serious of life-threatening illnesses. The FDA and other U.S. governmental agencies also have taken steps to promote the development and availability of drugs for rare diseases, including making these products available to patients who are in need, even before the drugs have full FDA marketing approval.

The relative efficacy of vestibular-proprioceptive stimulation and the upright position in enhancing visual pursuit in neonates.

48 healthy neonates born to multiparae were randomly assigned to view a moving stimulus either in the horizontal or the upright position, with or without added vestibular stimulation and with or without pacifier sucking. The infant was shown a moving black line inside a strictly controlled visual environment provided by an apparatus which permitted horizontal and upright positioning and displacement of the infant. Visual tracking was recorded by a concealed TV camera positioned at a constant distance and angle from the infants' eyes in both positions. Quality of tracking during each of 4 trials was scored on a 7-point scale. Results indicate that vestibularproprioceptive stimulation provided to the infant either horizontally or semivertically significantly enhanced his visual tracking, whereas the upright position did not. Pacifier sucking also improved his performace.

Effects of waterbed flotation on premature infants: A pilot study.

Two types of waterbeds were developed to impart compensatory vestibular-proprioceptive stimulation to premature infants. Twenty-one infants ranging in gestational age from 27 to 34 weeks and birthweights from 1,050 to 1,920 gm were included in this pilot study. Assignment to experimental and control groups was made by random design. The experimental group consisted of ten infants who were placed on a gently oscillating waterbed before the sixth postnatal day, where they remained for seven days. Their clinical progress was compared with that of a control group of 11 similar babies. Waterbed flotation was found to be a safe procedure; there was no significant effects on the infants' vital signs, weight, or frequency of emesis. Highly significant differences were found in the incidence of apnea between the two groups, with infants on the oscillating waterbed having significantly fewer apneic spells. Infants placed on the waterbed during the first four postnatal days benefited more than those placed later. A non-oscillating waterbed was found clinically useful for very small prematures with severe skin problems, for infants recovering from abdominal surgery, and for infants receiving parenteral nutrition.