Therapeutic neglect

Purpose The Therapeutics for Rare and Neglected Diseases (TRND) program was established in 2009 to encourage and accelerate the pre-clinical development of therapeutics directed at rare and neglected diseases. These are diseases that are classified as effecting fewer than 20,000 people in the United States at a given time, and are also known as orphan... 

There are really only three possible routes (1) use the commercial market through the patent system to determine the rewards to the innovator, (2) base rewards to innovators on therapeutic benefits, and (3) do not bother measuring at all. Option (1) is the patent system, but this functions poorly for neglected diseases. Advanced Purchase Commitments use option (2) in a half-hearted way, as I describe below. A system of Transferable Intellectual Property Rights, described below, uses option (3). The key issue is that in the absence of meaningful measurement of health impacts, it is necessary to base rewards only on commercial success, and that is not consistent with a mission to improve the health of the poor. 

Investing in research on drugs for neglected diseases may offer immense therapeutic benefits. There appears to be willingness to invest quite considerable... 

Exercise is an essential yet neglected aspect of treatment for type 2 diabetes especially in its early stages where insulin resistance may predominate. Accumulation of at least 30 0 minutes of moderate physical activity on most days of the week is recommended. For type 1 diabetes the emphasis must be on adjusting the therapeutic regimen to allow safe sports participation to prevent precipitation of ketoacidosis or hypoglycaemia. Extra care is required in cases with known complications like proliferative retinopathy, nephropathy, foot ulcers and cardiac or peripheral vascular disease. 

Focus of the big pharma industries on developing we too blockbuster drugs in largely exploited therapeutic areas and neglect of acute diseases. 

Excipients are thus one of the three components that in combination produce the medicine that the patient will take. In therapeutic terms, the API is of primary importance because without it there is no treatment and no product. However, in terms of the development and manufacture of the product, all three components are equally important, and we neglect any one of them at our peril. The annals of formulation development in most companies, both large and small, are probably littered with examples where some aspect of one of these three components has been neglected in some way, with unfortunate consequences for the project. The interactions between excipients and the other two components (the API and the manufacturing process), and/or between two or more excipients, are fundamental to the transformation of an API into a medicinal product. 

An assumption concerning the number of compartments is, by nature, not required. For reliable results and precise parameter estimates, however, a relatively large number of data points per individual are required. Phase 1 studies of mAbs usually provide sufficient data for a noncompartmental analysis, but the assumption of linear pharmacokinetics is not valid for most mAbs. This prerequisite, however, was frequently neglected during the early years of therapeutic mAh development, and an overall estimate for CL, for example, was frequently reported in the literature. In dose-escalating studies, however, the concentration-time plots of the raw data clearly indicate that the slope of the terminal phase is not parallel for the different doses, but increases with increasing dose (Fig. 3.10). As a result, the listing of different clearance values for different doses can be found. For example, the clearance of trastuzumab was reported to be 88.3 mL/h for a 10-mg dose, 34.3 mL/h for a 50-mg dose, 25.0 mL/h for a 100-mg dose, 19.0 mL/h for a 250-mg dose, and 16.7 mL/h for a 300-mg dose. 

Several studies demonstrate the effectiveness of antiseptic therapy in AD it may be administered either as part of emollients or as wet wrap dressings (see Table 30.1). However, antiseptic therapy is only one part in the successful management of AD by reducing the risk factor S. aureus, other therapeutic strategies cannot be neglected. 

MAOIs should not be neglected as therapeutic agents for the treatment-resistant... 

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