Tough times ahead for big pharma?
Currently it’s the financial industry that is in trouble. Will the pharmaceutical industry be next? This could well be according to business analysts, in a recent report in the Financial Times.
The reasons for the bad prognosis are expiration of patents coinciding with shrinking pipelines and increasing competition from generics. Furthermore, the counterstrategy of mergers and acquisition isn’t seems to be working as expected.
Meanwhile, drug regulations are getting tighter. Alternative medicine, dietary supplements, and homeopathic medications are conquering the market while biotechnology and stem cell research are not delivering the promised blockbuster therapies everybody is hoping for.
In 2007, Roche outperformed for the first time its Swiss archival Novartis in earnings. However, even Roche delivered lower than expected results in the first quarter of 2008 due to decreasing demand for Tamiflu.
Other drug companies are expecting tough times as the patent of their blockblusters are about to expire. GSK’s Lamictal goes off patent this year and Pfizer’s Lipitor in 2010. Other best-selling drugs whose patents are due to expire are Johnson & Johnson’s Risperdal, Astra Zeneca’s Seroquel and GSK’s Avandia, according to FT.
Sunny treatment for diseases: updates on vitamin D deficiency and sufficiency
Sunshine is the major source of vitamin D, an essential vitamin synthesized by skin exposure to sunlight. So how can vitamin D deficiency be a global problem? Below is a review of recent research on the benefits of vitamin D and possible causes of its deficiency.
Vitamin D and Alzheimer’s disease [1]
A small retrospective study (n= 32) found strong links between low serum levels of vitamin D and low performance in cognitive tests in patients with Alzheimer’s disease. Supplementation with vitamin D improved test outcomes. The results suggest that optimal vitamin D levels are important in cognitive function in older adults.
Vitamin D and myopia [2]
Vitamin D deficiency is linked to myopia in the Asia-Pacific region. Results show that 90% of conscription-aged Singaporean males are myopic. This is a dramatic increase compared to the incidence of 20 to 30% about 40 years ago. In Australia on the other hand, the incidence went from 15% to 20-25% within the same time period.
Ethnicity may play a role because of the “genetic susceptibility to environmental risk factors associated with intensive education and urbanisation” among East Asians. However, myopia seems equally prevalent across all ethnic groups (including Malay and Chinese) in Singapore.
Furthermore, the prevalence of myopia was found to be 10 times more among Chinese-Singaporean children than Chinese children based in Sydney. The difference lies in the number of hours of exposure to the sun. The Australian children stayed outdoors 4 times longer than their Singaporean counterparts. Researchers hypothesize that exposure to sunlight encourages the release of dopamine, which in turn inhibit excessive eye growth that leads to myopia. In many Asian countries, sun exposure is actually avoided due to a cultural preference for lighter skin.
Vitamin D and multiple sclerosis [3]
Multiple sclerosis is strongly linked to genetics. However, there are strong geographical patterns in the incidence of multiple sclerosis that cannot be fully explained by genetics alone. It has been observed, for example, that multiple sclerosis is less prevalent in the tropics and subtropics than in higher latitudes. Environmental factors are involved in the epidemiology of this disease and one of these is vitamin D.
Vitamin D3and osteoporosis [4]
Vitamin D plays a major role in the prevention and management of osteoporosis. Vitamin D deficiency has been linked to osteopenia, osteoporosis and osteomalacia. Cholecalciferol or vitamin D3 enhances the absorption of calcium and phosphorous in the intestine.
Vitamin D and pregnancy [5]
Vitamin D during pregnancy can lead to craniotabes or softening of the skulls in newborn infants. This deficiency may persist one month after delivery especially among breastfed babies. This probably the reason behind prescription of vitamin D supplement to breastfed infants in many countries.
Vitamin D synthesis in the skin is influenced by “season, latitude, skin pigmentation, sunscreen use, clothing and aging” [4] as well as lifestyle and cultural preferences [2]. To prevent deficiency, appropriate exposure to sun should be encouraged. A daily supplement of 800 to 1000 IU of vitamin D3 may also help.
Sources:
- Przybelski RJ, Binkleya NC. Is vitamin D important for preserving cognition? A positive correlation of serum 25-hydroxyvitamin D concentration with cognitive function. Arch Biochem Biophys. 2007; 460(2):202-205
- Nowak R. Lifestyle causes myopia, not genes. New Scientist 2004.
- Ascherio A, Munger K. Epidemiology of Multiple Sclerosis: From Risk Factors to Prevention. Seminars in Neurology 2008; 28: 017-028.
- Holick MF. Optimal vitamin D status for the prevention and treatment of osteoporosis. Drugs and Aging, 2007; 24(12): 1017-29.
- Yorifuji J et al. Craniotabes in normal newborns; the earliest sign of subclinical vitamin D deficiency. Journal of Clinical Endocrinology & Metabolism February 12, 2008.
Neurological effects of traffic pollution
The link between air pollution and respiratory disorders is quite well known [1]. The association between air pollution and cardiovascular diseases has been reviewed in a previous post.
The latest research on air pollution looks into the neurological effects with following results:
Air pollution and brain function [2]
Exposure to diesel fumes triggers a stress response in the human brain. Researchers were able to demonstrate this using dilute diesel exhaust fumes (300 µg/m3) as model for ambient particulate matter exposure and monitoring brain activities by quantitative encephalogram (QEEG). In this double-blind randomized crossover study, those exposed to diesel exhaust showed a significant increase in the median power frequency of the QEEG after 30 minutes of exposure. This functional response in the brain continued to rise with longer exposure.
Air pollution and children`s IQ [3]
Children exposed to traffic-related pollution perform poorly in intelligence and memory tests compared those who breathe cleaner air. This prospective birth cohort study looked into children`s exposure to black carbon, a particulate matter component generated by traffic vehicles. Heavy exposure to black carbon translated to drops in averages scores in intelligence, vocabulary, memory and learning scales and indices. “Higher levels of black carbon predicted decreased cognitive function across assessments of verbal and nonverbal intelligence and memory constructs.”
It is speculated that “ultrafine” or “nanoparticles” found in the environment translocate to the brain and cause increased oxidative stress and brain inflammation.
Sources:
1 Andersen et al. Ambient Air Pollution Triggers Wheezing Symptoms in Infants. Thorax.Published Online First: 11 February 2008
2. Cruts et al. Exposure to diesel exhaust induces changes in EEG in human volunteers. Particle and Fibre Toxicology. Particle and Fibre Toxicology 2008, 5:4.
3. Franco Suglia et al. Association of black carbon with cognition among children in a prospective birth cohort study. American Journal of Epidemiology 2008 167(3):280-286.
The year that was: major events in 2007
Nature`s Daniel Cressey listed several events as among the most newsworthy in 2007. Some of these events are discussed below.
Biotechnology
November was a good month for biotechnology. American and Japanese researchers derived pleuripotent stem cells from human skin. American researchers also finally succeeded cloning primate embryos in the same month. Both events are major breakthroughs in stem cell research.
This year, two big names in genomics - James Watson and Craig Venter – had their full genome sequenced. In the meantime, American start ups are offering personalized genetic information service (see October post).
Climate Change
The Intergovernmental Panel on Climate Change (IPCC) was co-winner of the Nobel Prize for Peace. In the meantime, the Northwest Passage that connects Atlantic and Pacific Oceans was practical ice-free and passable – a record low in the arctic ice cover. If the IPCC reports and this ice shrinkage do not convince people of the reality of global change, nothing ever will.
Pharmaceutical scandals
China’s former head of food and drug regulatory agency was executed in July after having been convicted of corruption. In the USA, the Avandia scandal rages on. The USA FDA required an additional black box warning for the diabetes medication Avandia (rosiglitazone) labelling last year but Avandia`s troubles didn’t stop there. The latest involved a US senate inquiry and a leak by an NEJM reviewer.
Safety issues
The July earthquake in Japan caused a leak in a major nuclear reactor, reawakening concerns over nuclear energy safety in general.
Two incidences of major biosecurity lapses were reported this year. In the UK, a leaky pipe caused an outbreak of foot-and-mouth disease. In a bioweapons research lab at the Texas A&M University, researchers were exposed to biohazards.
Space technology
Japan and China launched moon probes in 2007 though there were doubts whether China’s claims of success were authentic. China also tested a space weapon by shooting at one of its defunct satellites, scattering potentially dangerous debris in space.
Wired magazine considered the following as the top 10 scientific breakthrough of 2007:
10. Transistors Get Way Smaller
9. Scientists Clone Rhesus Monkey to Produce Stem Cells
8. Planet Discovered That Could Harbor Life
7. Engineers Create Transparent Material as Strong as Steel
6. Soft Tissue from T. Rex Leg Bone Analyzed
5. Laboratory Mice Cured of Rett Syndrome
4. Enzymes Convert Any Blood Type to O
3. Mummified Dinosaur Excavated and Scanned
2. Chimpanzees Make Spears for Hunting
1. Researchers Turn Skin Cells to Stem Cells
References:
Cressey D. News 2007. Nature 450, 1134-1135 (2007)
Rowe A. Top 10 Scientific Breakthroughs of 2007. Wired 27 Dec 2007.
“Something is rotten in the state of…
…science” if I may borrow from and rephrase Shakespeare.
The highest ethical standards – we expect no less from men and women of science. Yet, recent events brought to light just how short they can fall from these expectations.
“Neither a borrower nor a lender be: For loan oft loses both itself and friend.”
Case # 1: Duplication and plagiarism.
Borrowing from the works of others and our own without proper citation is, in the scientific community, unethical behaviour of the highest magnitude. Using the software eTBLAST, bioinformatics searched through 62,213 Medline entries and found 0.04% cases of potential plagiarism and 1.35% cases of potential duplication [1, 2]. These citations are recorded on Déjà vu, a database of potentially duplicated and plagiarized scientific articles.
One of its first victims comes from no less than that icon of higher learning – Harvard itself. Two review papers, published about 1 year apart by different authors in 2 different journals have 55% similarity [3].
The countdown is running for other papers listed in the Déjà vu database as scrutiny continues. The journals are suddenly waking up to the fact that unethical behaviour in science is more rampant than previously thought. But isn’t it ironic that anti-plagiarism software - the very tool that academia is using to prevent plagiarism by students – is the one that would cast serious doubt on scientific credibility?
“To tell, or not to tell, — that is the question.”
Case #2: Breach of confidentiality.
A referee for the New England Journal of Medicine committed a major breach of confidentiality by leaking an unfavourable manuscript to a drug company [4]. I’m referring to the Avandia (rosiglitazone) issue (see 25 Nov 2007post) and how a referee faxed a copy of the manuscript [5] to the drug’s manufacturer GSK before it was officially published. The confidentiality of the peer review process is sacrosanct and breaching this confidentiality is a major scientific misconduct.
This reflects current concerns about conflicts of interest among authors, editors, and referees (who are most of the time, all one and the same) due to financial support from pharmaceutical companies. Another reason to call for non-industry-sponsored clinical research.
“There is nothing either good or bad, but thinking makes it so.” And getting caught.
References:
[1] Errami M et al. (2008). Déjà vu—A study of duplicate citations in Medline. Bioinformatics 24(2):243–249.
[2] Errami M & Garner H (2008). A tale of two citations. Nature 451:397-399.
[3] http://www.boston.com/news/health/blog/2008/01/a_harvard_rheum.html
[4] Vastag B (2008). Reviewer leaked Avandia study to drug firm. Nature 451:509.
[5] Nissen SE & Wolski KN (2007). NEJM 356:2457–2471.
Cluster of human avian flu cases in Pakistan
The recent H5N1 outbreak in Pakistan causes much concern because it is the largest cluster of human cases of the avian flu since 2006 in Indonesia. 8 suspected cases have so far been reported in the outbreak, 2 of which were fatal.
The World Health Organization, in cooperation with Pakistani health officials, is closely monitoring the area, as well as checking hospital and clinic registers for possible unreported retrospective cases. Cases clustered closely in a small geographical area are highly crucial in the epidemiological monitoring of avian flu because they may represent cases of the human-to-human transmission of the disease. To date, transmission has only been reported from animal-to-animal and from animal-to-human.
Nature News, 17 Dec 07
WHO news, 15 Dec 07
Photo credit
Inequality in global healthcare
Over 230 science journals from 37 countries simultaneously published articles last week (October 22, 2007) which focused on global poverty and development. This was possible through the initiative of the Council of Science Editors which organized the “global theme issue on Poverty and Human Development” to promote awareness of this topic, especially in developed countries [1].
Over 750 articles were published globally, including many scientific and medical research conducted in developing countries.
One of participating journals, the British Medical Journal (BMJ), particularly focused on reports on healthcare issues in different countries and the apparent disparity in health services between developed and developing countries [2].
Other topics touched upon are: “childbirth safety, HIV/AIDS, malaria treatment, food insufficiency and sexual behavior, environmental and nutritional interventions to improve child survival, physician brain drain from the developing world, and altered immunity and influenza’s impact on poor children.” [1].
Photo description: Cover of BMJ issue