Kelvin Teo
Photo courtesy of Salvodonica, Flickr
In recent years, Singapore lawmakers have sought to establish Singapore as a leading centre in the area of Biomedical Sciences through a slew of investments that saw the construction and subsequent staffing of research facilities. One of the key areas of research expertise that our authorities would like to develop is in the realm of drug discovery. To this end, the Experimental Therapeutics Centre (ETC) was established under the auspices of the Agency for Science, Technology and Research (A*STAR). How the process of drug discovery works is that the science of how the drugs work begins in the test-tube, and is then tested on animal models, and subsequently humans in clinical trials. If the drug was shown to be effective (the technical term for it is efficacious), it will be established as a therapy for the condition that it is intended to treat. Thus, the raison d’etre of ETC is to fuel the drug discovery process.
What are the obstacles to the development of drugs? The first obstacle is in the science of the entire process. Drugs that hold promise in the test tube, and even in animal models may not produce any therapeutic effect, or worse produce toxic effects in humans. The drug may fail in any step of the development process, which is why the price tag for an investment into the drug development process from discovery to clinical trials may run into the billions, if we factor in the costs of those that have failed. The other obstacle that is faced in the development of new drugs even if they pass all the hurdles of Research and Development (shown to be therapeutically effective in humans) is to demonstrate their superiority over the current drugs that they are seeking to replace, which are usually cheaper. The superiority has to be proven, especially if such a drug wants to make it to the list drugs that are subsidised (subsidised drugs will mean more patients will elect for the treatment and higher demand of course), an example of which is the Pharmaceutical Benefits Scheme (PBS) in Australia. In order for a new drug to make the PBS list, it not only has to be more effective than current treatments, but has to undergo direct costs considerations such as whether the new drug does improve the patient’s quality of life and whether the additional cost in funding the treatment is worth the benefit. The new drug also has to undergo indirect cost considerations such as the effect of the drug on the patients’ occupational status which includes his productivity and ability to contribute to the economy.
The third obstacle is the competition for talents. There are top research centres and institutions worldwide that attract the best of brains by virtue of a prestigious reputation, and naturally require prospective researchers to be competitive and highly qualified. Top research centres staffed by top brains would have a competitive advantage over those whom are not considered major players in Research and Development. With top research faculty, these top research centres are likely to be leaders in drug discovery research, and the reality is that the top centres will always be a magnet for top brains. All research centres including ours are in competition for research talents, and the competition we face with top research centres worldwide in the areas of drug development is stiff.
In terms of drug discovery research, we face stiff competition, and thus, the question is whether there is any other areas within the medical field in which we can have a competitive advantage. The answer is yes. For a fact, we are considered an immigrant society, with our forefathers hailing from India and China, whilst the Malay ethnic group was the original inhabitant of Singapore. Our forefathers would have handed down their knowledge of traditional medicines that their respective ethnic groups have used, and even in this day, surveys have shown that majority of us the descendants have used what our forefathers have taught us to treat ourselves whenever we are sick.
Thus, each major ethic group in Singapore would have its own brand of traditional medicine – traditional chinese medicine (TCM), traditional malay medicine (TMM) and traditional indian medicine (TIM). In addition, it is possible for an individual from one racial group to utilise the traditional medicine of another racial group, for instance, a chinese Singaporean may rely on traditional chinese medicine, but occasionally can try out the ayurvedic practices of traditional indian medicine.
Our medical world is conventionally dominated by allopathic medicine, or better known as western (or conventional) medicine. In the past, western medicine has casted a skeptical eye on traditional methods such as TCM or TIM. Emerging research has demonstrated the therapeutic potential of certain traditional medical methods. For instance, there is evidence from clinical studies that acupuncture is able to treat dysmenorhhoea or otherwise known as menstrual cramps in women. And there is some evidence that acupuncture can be used to treat pain. Research on animal models have also shown that a particular species of plant used in ayuvedic medicine has anti-allergy properties. Curcumin, which is used extensively in ayurvedic medicine was found to have potential anti-cancer properties in head and neck cancer.
Traditional medicines of this kind are not considered replacements for conventional therapies. And hence, the correct description for them is complementary medicine, where they are used in complementary with conventional medicine. Although there is evidence that certain traditional medical methods have therapeutic potential, one has to realise that the evidence for such methods usually do not lie on the highest echelons of the evidence-based medicine pyramid. The highest echelon on the evidence-based medicine pyramid is what is as systemic reviews of clinical trials, and what constitutes such is the review of evidence presented in the trials, and involves thorough scrutinisation of the way the trials are carried out. Hence, these reviews carry a lot of weight on evaluation and evidence of the effectiveness of a therapy. Randomised controlled trials, which provide evidence for the therapeutic effect on human patients occupies the next hierarchical level of the pyramid.
Systemic reviews of traditional medical methods have actually revealed shortcomings in the way the trials involving traditional medical approaches were carried out. Such trials usually involved small numbers of patients. The issue with a small patient sample is that it may not be representative of the population at large. Which means, we cannot really say that just because a particular therapy works for a small group patients will mean it may work for the population at large. The other issue is the design of controls for experiments, especially for acupuncture, where there is difficulties in design of a control or placebo group, specifically with regards to what kind of ‘treatment’ the control group will receive. There is also the issue of the different formulations of herbal remedies – a particular research centre investigating the use of one particular formulation of herb may differ from another type of formulation that is used by another centre, thereby adding to the difficulties in interpreting results across the board from a variety of different centres.
Thus, the pertinent question is how Singapore can establish itself as a niche in complementary medicine research? The competitive advantage lies in Singapore’s multi-racial society comprising chinese, malays, indians and those falling outside the three ethnic groups. According to an editorial published in the Annals of the Academy of Medicine, 76% of 399 respondents in a household survey had used complementary medicine over a period of 12 months. Among the racial groups, 84% of chinese use complementary medicine, as compared to 69% malays and 69% of indians respectively. TCM (88%) was found to be the most widely used, followed by traditional Malay (Jamu) medicine (8%) and traditional Indian (Ayuverdic) Medicine (3%).
Thus, how can we achieve a niche in complementary medicine research? Basically, we can envision a goal of being a research centre of excellence in the role of complementary medicine and its combination with western medicine in order to produce favourable health outcomes, especially in a population like ours where majority are users of complementary medicine. For consistency of research, at the health policy level, formulations of complementary medicine, especially herbal concoctions must be standardised. And efforts should be directed at encouraging general practitioners, family doctors or our hospitals to engage with families on the topic of complementary medicine. This will include encouraging patients to give a detailed history of their usage of complementary medicine, and following up with them at regular intervals. The level of research into the influence of complementary medicine on health outcomes must be rigorous and consistent, and as far as possible, the shortcomings plaguing traditional medicine research as pointed out in the systemic reviews should be avoided. Research could be improved by having more patient participation, and better experimental design such as having better control groups to compare the patients.
Singapore has set itself the goal of being a biomedical hub with resources devoted to the establishment of research institutions similar to those from leading nations in biosciences research. The field of drug discovery research is indeed lucrative, and it isn’t surprising that our authorities have identified it as an area of interest. There are obstacles though, not only unique to Singapore but which also affect other similar centres elsewhere who are involved in such a research. Thus, another potential area in which Singapore can establish a niche expertise in is research into complementary medicine, and how it interacts with conventional medicine and the impact on health outcomes. It is interesting that Health Minister Mr Khaw Boon Wan’s speech for Budget 2011 was on a similar frequency as the thrust of this article.
Khaw asked two rhetorical questions:
The reality of the situation is that now the Chinese researchers are using conventional methods of evidence-based medicine to test the effectiveness of TCM, and this includes animal models all the way to clinical studies, even to the extent of publishing in western medical journals. Khaw also broached on the possibility of establishing Singapore as an information centre for adverse (unpleasant) effects of TCM. It is definitely within our means to achieve the vision articulated by Khaw, not even for TCM but for other forms of traditional medicine practised by the main ethnic groups in Singapore. And we can achieve more than just being an information centre for the adverse effects of traditional medicines. Given our population-base and the tendency to resort to usage of traditional medicines and combined with a rigourous approach of research, we can carve out a niche in complementary medicine research, including how the latter interacts with conventional medicine, and be at the forefront of it.
it is a slanted way of looking at TCM,ayuverdic and jamu medicine as complementary and western medicine as the main course.
afterall, the proof of the pudding is in the eating, as they are all proven to work from various clinical practices over the years, why still relegate them to second class status, if not to protect the status of western medicine and its doctors.
Cy, it will probably take time for traditional medicines to achieve main course status for the following reasons…
1) In order to succeed conventional/western medicines, it has got to go through the same scientific rigour as that of western medicine, and I am referring to pre-clinical and clinical trials, which are what the Chinese in PRC are doing right now.
2) There is a need for standardisation of traditional medical practices including drug concoctions. If one centre uses one formulation and the others use other formulations, it is hard to make conclusions about the effectiveness of the method. And thus from the medical regulatory viewpoint, it is a valid concern.
3) This point is the consequence of the first two points, there is a need to apply a high level of scientific rigour in the approach to Traditional Medicines..Currently, what you mention about traditional medicines working, those published papers only looked at a small patient sample. This differs from western drugs where there is a need to enrol a large patient sample representative of the population. One patient sample doesn’t provide a convincing level of evidence that the medicine can work for the whole population.
4) I don’t view the complementary label as something permanent. As I mentioned in the article, some Ayurvedic medicines have potential anti-cancer potential. And why is it considered complementary is because of my first three points – no clinical information in the scientific rigourous sense that those work. Thus, if certain traditional medicines like the one above has anti-cancer properties, complementary is a safe term to use to describe them is because it could be safer to say these treatment may help augment cancer treatment, in the absence of information from research that they actually cure and should be the main course. It is something to akin about how we judge people, when someone shows you his CV and has high GPA, you would probably think he is hardworking, but you would hesitate to conclude he is really hardworking. But after working with him, would you have a good evidence of whether he is hardworking.
Good ideas in general. The challenge here is the will to do things and the culture of larger scale scientific inquiry here (exam smart, smart but very little inclination to pursue long odds – the kind of mentality required to be successful at research). At least one major pharmaceutical tried in the 1990′s -2000′s to evaluate natural products. Maybe their approach wasn’t right but it wasn’t for lack of trying.
Research funding agencies here don’t have a suitable mentality to follow up on your suggestions (fixated on short term returns of investments). They don’t appreciate that the western pharmaceutical industry was built from years of effort in chemistry and tinkering. Tinkering is not encouraged here.
When conventional Western medicine seeks out new drugs from an herb, it attempts to isolate and extract the so-called active ingredient. It has been found that this can result in serious side effects during usage.
From personal experience I found that the use of even dietary supplements like garlic extract, Quercetin or Bromelian extracts found in fruits like pineapple results in some troubling side effects like bleeding otherwise completely not experienced when taking the actual herb or fruit.
As one doctor who uses alternative medicine advises on the Internet: “Some danger might exist in taking herbal extracts because they do not contain the whole spectrum that Mother Nature provides in the actual herb.”
Conventional medicine is not just about controlled research but also about the pharmaceutical companies wanting to patent and control the distribution of their drugs. Hence even though they know that many natural herbs are efficacious, they cannot go the way of the traditional herbal medicine given that it can never patent a herb.
The biomedical research that the Singapore government has spent $100′s of millions if not $billions is just a pet project of some politicians who continue to think they are good in business. How can it succeed given that it has to the go the expensive Western pharma way and secondly there is no way it can compete with research institutions in the West which are decades ahead?
The writer correctly pointed out: ” … the price tag for an investment into the drug development process from discovery to clinical trials may run into the billions (of dollars)”.
As an industry is this sustainable in the long run? The answer may well explain why drug industry has seen much consolidation over the last 2 decades.
Western medicine may be the main course now but more importantly for society is the question of how to make healthcare more efficient and sustainable cost-wise. This has become a universal issue for developed and developing nations.
Complementary Medicine has always been part and parcel of Singapore and other Asian societies. But that is not enough. What they need to go for is Integrative Medicine where Western medicine is practised side-by-side with alternative medicine. I guess that this is what China and India are doing.
Doctors should be trained in both but such a suggestion is going to raise hackles from the Western medical community given that every school of thought has its own share of bigotry.
Still, I would add that Western medicine is so trusted nowadays that even when you consult a TCM physician for so much as an intestinal complaint, you might be asked if you have gone for a check by a Western doctor even. Such is the aura surrounding Western medicine.