Correspondence

Drug development output: what proportion for tropical diseases?

Cancer biomarkers represent a revolutionary advance toward personalised cancer treatment, promising therapies that are tailored to subgroups of patients sharing similar generic traits. Notwithstanding the optimism driving this development, biomarkers also present an array of social and ethical questions, as witnessed in sporadic debates across different literatures. This review article seeks to consolidate these debates in a mapping of the complex terrain of ethical and social aspects of cancer biomarker research. This mapping was undertaken from the vantage point offered by a working cancer biomarker research centre called the Centre for Cancer Biomarkers (CCBIO) in Norway, according to a dialectic move between the literature and discussions with researchers and practitioners in the laboratory. Starting in the lab, we found that, with the exception of some classical bioethical dilemmas, researchers regarded many issues relative to the ethos of the biomarker community; how the complexity and uncertainty characterising biomarker research influence their scientific norms of quality. Such challenges to the ethos of cancer research remain largely implicit, outside the scope of formal bioethical enquiry, yet form the basis for other social and ethical issues. Indeed, looking out from the lab we see how questions of complexity, uncertainty and quality contribute to debates around social and global justice; undermining policies for the prioritisation of care, framing the stratification of those patients worthy of treatment, and limiting global access to this highly sophisticated research. We go on to discuss biomarker research within the culturally-constructed ‘war on cancer’ and highlight an important tension between the expectations of ‘magic bullets’ and the complexity and uncertainty faced in the lab. We conclude by arguing, with researchers in the CCBIO, for greater reflexivity and humility in cancer biomarker research and policy.

There are several new treatments and vaccine technologies in clinical development for childhood malaria that have arrived in the clinical phase of evaluation during the past 5–10 years. This is a long-awaited change as until this time there had been little in the pipeline. As these products progress, evaluating them in the populations for whom they are being developed is becoming increasingly challenging. Many more capable trial sites are required and thousands of children and their parents need to be willing to take part in all the clinical trials that will be necessary if even a handful of these products make it through to obtaining a marketing approval license. Then, beyond licensure, these products will need to be assessed in more ‘real-life’ phase IV trials to establish whether they can truly impact the high level of mortality that malaria brings to the under-five population in Africa. Here we explore the issues that face both the trial sites and the product developers and present how this opportunity should be utilised to develop experienced African clinical researchers and facilities alongside getting these products through into public health use.

Synthesis of new Palladium(II) and Ruthenium(II) complexes of the type, [Pd(L)Cl₂] and [Ru(η⁴-C₈H₁₂)(L)Cl₂] {where, L = thiosemicarbazones derived from 5-nitrothiophene-2-carboxaldehyde and cycloalkylaminothiocarbonyl hydrazines} have been isolated by the reaction of [Pd(DMSO)₂Cl₂] and [Ru(η⁴-C₈H₁₂)(CH₃CN)₂Cl₂] with 5-nitrothiophene-2-carboxaldehyde thiosemicarbazones. The spectral data revealed that the thiosemicarbazones act as bidentate ligands, making use of thionic sulphur and the azomethine nitrogen atom for coordination to the central metal ion. Microdilution method was used for the assessment of antiamoebic activity of all the compounds against HK-9 strain of Entamoeba histolytica. Among all the thiosemicarbazones, 5-NT-4-BPTSCN (3) showed significant antiamoebic activity (IC₅₀ – 2.56 μM). Enhancement of antiamoebic activity resulted by introducing palladium and ruthenium metals in the thiosemicarbazone moiety. All the Pd(II) and Ru(II) complexes of 5-nitrothiophene-2-carboxaldehyde thiosemicarbazones were found more active then their respective ligands. The complexes 1a-4a, 1b and 3b showed antiamoebic activity.

Despite some improvements in the health status of the world during the last few decades, major obstacles remain. Improvements in health outcomes have not been shared equally among countries and poverty is clearly the main reason. Infectious diseases, which remain the major cause of death worldwide, are an incalculable source of human misery and economic loss. In fact, 25% of all deaths and 30% of the global burden of disease are attributed to infectious diseases. Unfortunately, more than 95% of these deaths, most of which are preventable, occur in the developing world, where poverty is widespread. The 3 major infectious disease killers in these countries are HIV/AIDS, tuberculosis, and malaria. The principles of social justice and health as a human right in the developing world have been advocated as the main justification for health assistance from rich to poor countries. Although we do not disagree with this, we argue that a strategy that emphasizes the shared benefit to rich and poor countries would facilitate this process. We propose that the accomplishment of these challenging tasks should be viewed from the perspective of game theory, where the interests of the parties (in this case rich and poor countries) overlap. As the world becomes increasingly integrated, economic development in resource-poor countries will increase the opportunities for richer countries to profit from investment in the developing world. Global health has political and international security implications for the developed world, as well. In view of the current health status of the developing world, we are not playing a game but facing a matter of life and death. “When health is absent, wisdom cannot reveal itself, art cannot becomes manifest, strength cannot fight, wealth becomes useless, and intelligence cannot be applied” Herophilus, 325 bce (Physician to Alexander the Great)

The purpose of this article is to address the relationship between health, poverty, and development in the context of game theory. We will focus on the link between economic inequalities and health outcomes, exclusively concentrating our analysis on the impact of infectious diseases. Subsequently, we will outline the game, the players, and the potential win-win outcomes that may potentially result.

The pharmaceutical industry is accountable on the one hand to its shareholders and on the other to the community at large. These two obligations can, in principle, be met. However, the industry has developed practices that do not consider society, including excessive or inappropriate pricing of drugs, an indifference to the needs and limitations of the developing world, an imbalance between true innovation and promotional activity, interference with clinical investigations, and efforts to mould medical thinking and priorities as a means to enlarge the market. In such respects, the pharmaceutical industry must now be called to order. The industry has shown itself to be sufficiently resilient to adapt to change if society insists on it. However, to influence multinational corporations effectively, the efforts of governments will have to be complemented by others, notably the many voluntary organisations that have shown they can effectively represent society's public-health interests.