Common characteristics of open source software development and applicability for drug discovery: a systematic review

Background

Innovation through an open source model has proven to be successful for software development. This success has led many to speculate if open source can be applied to other industries with similar success. We attempt to provide an understanding of open source software development characteristics for researchers, business leaders and government officials who may be interested in utilizing open source innovation in other contexts and with an emphasis on drug discovery.

Methods

A systematic review was performed by searching relevant, multidisciplinary databases to extract empirical research regarding the common characteristics and barriers of initiating and maintaining an open source software development project.

Results

Common characteristics to open source software development pertinent to open source drug discovery were extracted. The characteristics were then grouped into the areas of participant attraction, management of volunteers, control mechanisms, legal framework and physical constraints. Lastly, their applicability to drug discovery was examined.

Conclusions

We believe that the open source model is viable for drug discovery, although it is unlikely that it will exactly follow the form used in software development. Hybrids will likely develop that suit the unique characteristics of drug discovery. We suggest potential motivations for organizations to join an open source drug discovery project. We also examine specific differences between software and medicines, specifically how the need for laboratories and physical goods will impact the model as well as the effect of patents.     

HIV infection and bone disease: implications for an aging population

Now more than ever, the management of age-related problems, from cardiovascular morbidity to bone pathology, is increasingly relevant for HIV physicians. Low bone mineral density (BMD) and fractures are more common in HIV-infected patients. Although a multifactorial aetiology underlies this condition, increasing evidence suggests a role for antiretroviral therapy in low BMD, especially upon initiation. This review will detail the epidemiology, pathogenesis, diagnosis and management of osteoporosis and low BMD in HIV-infected patients, with particular emphasis on aging.     

Mentoring: implications for career development

Mentoring can be viewed as a set of behaviors applied toward a relationship that provides guidance and support in career development. This article reviews some of the current literature on mentoring and presents concepts that may benefit persons in the profession of dietetics. The process of mentoring provides mentors with career and psychosocial rewards, while protégés benefit from a wide variety of career and/or social opportunities made available through the relationship. Rewards for each member of the dyad appear dependent on the age and needs of each person. An alternative to mentoring, known as the patron system, has been proposed; that system places mentoring at the end point of a continuum which includes peer pals, guides, and sponsors. Networking, a crucial aspect of career development, broadens opportunities for prospective mentors or sponsors and protégés to meet and interact. Entry-level dietitians can benefit from mentor-protégé relationships which groom young professionals for leadership positions. The question to be answered is how such relationships can be supported in our various work settings. A model of the mentoring process in dietetics is proposed.     

Genetics and roadblocks of drug resistant tuberculosis

Considering the extensive evolutionary history of Mycobacterium tuberculosis, anti-Tuberculosis (TB) drug therapy exerts a recent selective pressure. However, in a microorganism devoid of horizontal gene transfer and with a strictly clonal populational structure such as M. tuberculosis the usual, but not sole, path to overcome drug susceptibility is through de novo mutations on a relatively strict set of genes. The possible allelic diversity that can be associated with drug resistance through several mechanisms such as target alteration or target overexpression, will dictate how these genes can become associated with drug resistance. The success demonstrated by this pathogenic microbe in this latter process and its ability to spread is currently one of the major obstacles to an effective TB elimination.This article reviews the action mechanism of the more important anti-TB drugs, including bedaquiline and delamanid, along with new findings on specific resistance mechanisms. With the development, validation and endorsement of new in vitro molecular tests for drug resistance, knowledge on these resistance mechanisms and microevolutionary dynamics leading to the emergence and fixation of drug resistance mutations within the host is highly important.Additionally, the fitness toll imposed by resistance development is also herein discussed together with known compensatory mechanisms. By elucidating the possible mechanisms that enable one strain to reacquire the original fitness levels, it will be theoretically possible to make more informed decisions and develop novel strategies that can force M. tuberculosis microevolutionary trajectory down through a path of decreasing fitness levels.     

Genetics research and third parties: implications for education in the health professions.

Research that seeks information about the families of participants raises several questions regarding policy and the education of health professionals, including curriculum planning. The limits of individualism in health care and research, the moral grounding of informed consent and privacy and the moral and legal obligations of professionals in respecting them, the scientific promise and ethical perils of "geneticization," and responsible conduct in research are all topics to be included in the education of health professionals.     

Trends in nursing home expenditures: implications for aging policy.

Nursing home care has become a major governmental responsibility. Public expenditures for nursing home care amounted to $7.3 billion in 1977. They represented 57.2 percent of the $12.8 billion nursing home bill nationally and 12 percent of public spending on all personal health care. Nursing home care absorbs more than one-third of all Medicaid expenditures. This paper explores expenditure patterns in recent years and discusses some of the factors that will influence these patterns in the future. First we analyze recent trends over the five-year period ending 1977. Then we project future utilization based on current age-specific use rates. Finally, we review recent studies on the potential cost of savings of noninstitutional alternatives to nursing home care.     

Racializing drug design: implications of pharmacogenomics for health disparities

Current practices of using "race" in pharmacogenomics research demands consideration of the ethical and social implications for understandings of group difference and for efforts to eliminate health disparities. This discussion focuses on an "infrastructure of racialization" created by current trajectories of research on genetic differences among racially identified groups, the use of race as a proxy for risk in clinical practice, and increasing interest in new market niches by the pharmaceutical industry. The confluence of these factors has resulted in the conflation of genes, disease, and race. I argue that public investment in pharmacogenomics requires careful consideration of current inequities in health status and social and ethical concerns over reifying race and issues of distributive justice.     

Cerebral reserve capacity: implications for alcohol and drug abuse.

Cerebral reserve capacity (or functional reserve) refers to the brain's ability to maintain function when confronted by degenerative processes. Functional reserve can be estimated by several associated measures, including premorbid brain size, premorbid IQ, and level of education attained. There is accumulating evidence that the magnitude of reserve capacity is important in determining the onset and progression of the clinical manifestations of neurodegenerative brain diseases. Normal aging also whittles away at this cerebral reserve, and there may be a consequent unmasking of morbid effects that was not clinically evident when this compensatory reserve was sufficient. We review the evidence supporting this model for a number of degenerative brain processes, including Alzheimer's disease, presenile dementia, HIV dementia, aging, and chronic (multiyear) substance abuse. The concept of cerebral functional reserve has important implications for alcohol and drug abuse morbidity. First, given the high genetic contribution to substance abuse, there is an increased likelihood that the parents of substance abusers were substance abusers themselves. Substance abuse during pregnancy can inhibit brain growth, resulting in reduced brain size and reduced reserve capacity (and therefore less ability to compensate for loss of function later in life). Second, substance abuse is often coupled with poverty, and both substance abuse and poverty are associated with some of the same conditions that reduce brain growth. Finally, we comment on the most important public health implication of the cerebral reserve capacity model (vis-à-vis addiction).     

Calorie restriction and aging: review of the literature and implications for studies in humans

Calorie restriction (CR) extends life span and retards age-related chronic diseases in a variety of species, including rats, mice, fish, flies, worms, and yeast. The mechanism or mechanisms through which this occurs are unclear. CR reduces metabolic rate and oxidative stress, improves insulin sensitivity, and alters neuroendocrine and sympathetic nervous system function in animals. Whether prolonged CR increases life span (or improves biomarkers of aging) in humans is unknown. In experiments of nature, humans have been subjected to periods of nonvolitional partial starvation. However, the diets in almost all of these cases have been of poor quality. The absence of adequate information on the effects of good-quality, calorie-restricted diets in nonobese humans reflects the difficulties involved in conducting long-term studies in an environment so conducive to overfeeding. Such studies in free-living persons also raise ethical and methodologic issues. Future studies in nonobese humans should focus on the effects of prolonged CR on metabolic rate, on neuroendocrine adaptations, on diverse biomarkers of aging, and on predictors of chronic age-related diseases.     

Reference drug programs: effectiveness and policy implications

In the current economic environment, health care systems are constantly struggling to contain rapidly rising costs. Drug costs are targeted by a wide variety of measures. Many jurisdictions have implemented reference drug programs (RDPs) or similar therapeutic substitution programs. This paper summarizes the mechanism and rationale of RDPs and presents evidence of their economic effectiveness and clinical safety. RDPs for pharmaceutical reimbursement are based on the assumption that drugs within specified medication groups are therapeutically equivalent and clinically interchangeable and that a common reimbursement level can thus be established. If the evidence documents that a higher price for a given drug does not buy greater effectiveness or reduced toxicity, then under RDP such extra costs are not covered. RDPs or therapeutic substitutions based on therapeutic equivalence are seen as logical extensions of generic substitution that is based on bioequivalence of drugs. If the goal is to achieve full drug coverage for as many patients as possible in the most efficient manner, then RDPs in combination with prior authorization programs are safer and more effective than simplistic fiscal drug policies, including fixed co-payments, co-insurances, or deductibles. RDPs will reduce spending in the less innovative but largest market, while fully covering all patients. Prior authorization will ensure that patients with a specified indication will benefit from the most innovative therapies with full coverage. In practice, however, not all patients and drugs will fit exactly into one of the two categories. Therefore, a process of medically indicated exemptions that will consider full coverage should accompany an RDP. In the current economic environment, health care systems are constantly struggling to contain rapidly rising costs. Drug costs are targeted by a wide variety of measures. Many jurisdictions have implemented reference drug programs, and others are considering them. This paper summarizes the mechanism and rationale of RDPs, presents evidence of their economic effectiveness and clinical safety, and concludes with some practical implications of implementing RDP policies.