Richard Laing ~ Full interview

Medical officer at the World Health Organisation and author of the Priority Medicines for Europe and the World report

1.  What are in your view the current developments in the field of health?

The key developments are the emergence of chronic diseases in most developing countries of the world becoming the dominant burden of disease. And we are in the transition for some countries, but for many countries they have gone beyond their transition. So infectious diseases are now less significant and chronic diseases, particularly cardiovascular diseases, diabetes and respiratory related diseases, are of dominant importance as far as that goes. So that is the first point to pay attention to.

The second one is the growth of global funding agencies like the World bank, the Global Fund PEPFAR and the Clinton Foundation particularly in terms of HIV, TB and malaria they are willing to put up very large funds of money to ensure that poor people in poor countries have access to essential medicines for HIV, TB and malaria. That is a very large change. We never had such an amount of money available for pharmaceutical expenditures in that way.

The third area I think which is frequently forgotten is the decline in innovation that we have seen from the big pharmaceutical companies. The number of new clinical entities been registered by the pharmaceutical industry has declined very dramatically since the late 80s and early 90s. And the significance of that is that it means that we do not have the number of medicines coming online that we need to have available for poor people. So, when we say: which of the essential medicines are on patent, then the reality is that there are very few, and the number is decreasing. It is very hard to say with the exception of antivirals which are the medicines that really should be on the essential list of drugs if they were available for cheaper prices. It is very hard to make a case that any truly essential medicine are not on the essential drug list for reasons of costs.

I think those are three related issues that people need to pay attention to as far as this discussion is concerned.

2.  The first and third development can be seen as a problem. But the second development is quiet good, right?

Yes. It is a good development so far it is focussed on particular diseases with a high political profile. And in many circumstances these may not be the diseases that a country should focus on. For a country like India although it has 5 million AIDS patients or 3 million depending which survey you respond to, they have tens or hundreds of times more patients of cardiovascular diseases or smoking related diseases or with diabetes. And so in terms of the burden of diseases the displacement that has happened. We have what we call Millennium Goals that almost entirely neglected chronic diseases, particular mental health diseases and diseases related to other chronic diseases. So, there may well be a feeling that the world is doing a lot for developing countries, and clearly they´re spending a lot but are they spending it to the areas of the greatest need? This is a question that easily can be asked for all of the regions of the world except Africa. I think for most of Africa focusing on aids, TB and malaria is appropriate. But applying the same approach to South America or to Asia is far more problematic.

3.  And what kind of solutions do you see for these three issues?

I think for the changing burden of disease putting an emphasise on prevention and to try to prevent the emerging of cardiovascular disease and to some extent diabetes is very important I think. Trying to shift the funding is often not something that can be done on a global level. It is something we need to shift at the country and regional level. We have to shift the attention of countries and regions to the importance of chronic diseases and the treatment of those diseases.

4.  And the decline of innovation at the pharmaceutical companies, is there something we can do about that?

Well, I think that the work the TI Pharma is doing in the Netherlands has a lot of promise and it is investing in the higher risk research areas. I think what has happened is that the pharmaceutical industry has become very risk averse and part of the reason for that are the regulatory requirements of the regulators that pushed them down this direction. But what I think we see with the TI Pharma is the willingness to invest in the science that is far more risky and far less likely to achieve outcomes. That it is in these investments in these high risk technical areas that we will see major innovations happening. I think that the regulatory barrier to innovation is a problem and I think that the reason for that is a lack of attention to the pharmaco-vigilance for post marketing evaluation of medicines. But safety cannot be guaranteed trough clinical trials and through phase II and III trials. And we really need regulating agencies that need to grasp that concept and require, under all circumstances, conditional release that all medicines should be considered unsafe for at least 3 to 5 years after release.

I argue for a publically funded post marketing surveillance system where all exposures and adverse events for these new medicines would be tracked. So, in developed countries wherever they are prescribing or clinical databases these should be linked for these new medicines. And in developing countries where new anti malarias or new AIDS medicines or new combination therapies are released we need to set up sentinel surveillance systems so that when people are exposed to these medicines clinical events that they face should be reported.

If we have that then there could be clearly in the companies interest to release medicines where they are unsure about the safety of the medicines but they would be aware that the medicines would be actively tracked. So that we wouldn’t have a Viox disaster or something like that. The problem we have is that the FDA has been leading the way of trying to assure that the medicines are safe for registration and then ignoring the medicines after registration. The EMEA has a much better approach of trying to promote pharmacovigilance and post marketing surveillance. And this is clearly to the benefit of pharmaceutical industry if there is public funding for this process. It makes no sense to have every single pharmaceutical company setting up his own unique post marketing surveillance system where they use common sources of information.

5.  Do you know how pharmaceutical companies think of this system?

Well, the pharmaceutical companies at the moment are required to do the extensive phase II and phase III clinical trials that are very expensive and take a long time. Now they are concerned to be asked to spend a lot more on unique phase IV post marketing surveillance. So they are resistant to it. The argument that I have made to regulators and particular EMEA which got a lot of acceptance is to reduce the requirements for phase II and phase III. Put public funding into phase IV and allow companies to release products on the market earlier, but allow products that are clearly labelled as ‘not yet proven safe’ which in fact all new medicines are when they first come to the market.

6.  Do you think that biotechnology can play a role in these issues and solutions we just discussed?

I am very sceptical of biotechnology, because of the costs of manufacturing biotech products. If the cost of manufacturing a product is directly related to molecular weight of the product: the larger the product, the more expensive and difficult is to manufacture, the less likely it is that you have generic companies that entering the market of that. I think for diagnostic biotech products are far more likely to be successful by using biotech products to identify genes or metabolic defects. I think that is an area where they have real promise. I think for therapeutic agents the costs of manufacture is very high, even for the richest countries in this world.

7.  Can you tell a little bit more about the role of biotechnology for diagnostics?

When you´re looking at particular diseases where there is range of responses up until now people have tended to look to these responses and say ‘Oh, that is the normal variation.’ But it is very likely that you have the range of type 1, type 2 diabetics where all hyperglycemics are required. But what you also find is that those type 2 diabetics end up needing insulin. So, diseases may well progress in different ways but they may well be different forms of diabetics or different forms of asthma and need different treatments rather then treating all the diseases the same.

8.  Are there any other applications of biotechnology in the field of health that may be helpful?

I think biotechnology and agriculture is of incredible promise for nutrient and food supplies in all sorts of different environments. But that is a very different and indirect approach. In health I remain sceptical. Another point is that the more specialised the treatment is the more expensive the unit cost is. We have seen this with orphan diseases. The cost to develop the medicine for 5 thousand patients is the same as the costs of developing a medicine for 5 million people. Spreading the costs over a few patients will drive up the costs for developing the medicine.

9.  What do you think about the pharma crops?

I am a very strong supporter. We´ve always had plant breeding and forms of biotech in plant breeding at the plant level. For instance many of the tea plants of the world all come from a single original crop.

10.  Can you name some necessary conditions for successful solutions of the issues we just discussed?

A more flexible, regulatory environment, particularly with an investment in the public post marketing surveillance for the safety of the products. Because it is totally unrealistic to think that clinical tests can provide adequate safety information. And people can live in an unsafe world as long as they know. But as long as regulators or companies spread messages that all the new medicines are safe, we should address this. I am in favour of using the existing molecules and to fixed dose combinations, for example the poly pill, combination of four different medicines useful for patients that had a heart attack, is a very sensible innovation that should be pursued and followed up.

10.  Do you think that biotechnological solutions should be placed higher or lower on the agenda?

For therapeutics I think they should be placed lower. The research is expensive and the likelihood of success is low. At the diagnostic side I am much more open to use biotechnology for improvements and treatment monitoring.

11.  What in your view are the differences between developing and developed countries?

It is easy to lump developing and developed countries to a single package. But the reality is that developing countries are very varied. China and India are developing very fast, but are still considered developing countries. What we see in these countries is a middle class very fast emerging with populations in excess to the whole of Europe. And they are suffering from chronic diseases and are facing all the mentioned problems. So within developing countries there are as many health problems as in developed countries.

12.  In the field of health biotechnology, are there any issues that will lead to debate?

In developing countries very little. The mass hysteria about gene technology and agriculture is much more likely to be significant than biotechnology in the health field. The rich people in developing countries will call for access to the products of biotechnology, but the inherent costs of those will mean that only the ultimate elite with a special health insurance can have this access. Five or ten years ago I was much more positive about biotechnology. But now I am very sceptical. And if it´s not going to make a difference, it´s not going to create a debate.

13.  What will the field of health look like in 20 years time?

In Asian countries, Latin America and South Africa the chronic and infectious diseases will be handled quite well. The Haiti’s will remain poor, but we have seen dramatic developments in Caribbean countries. I think the biggest health problem in the world in 20 years time remains Africa. The population in Africa will remain about 10% of the world population so is relatively low. But in terms of mortality and early death Africa will remain the area of greatest concern. A successful vaccine against malaria may dramatically transform of Africa, but vaccinations for TB or AIDS I do not think will be successful in twenty years.

The chronic diseases will likely to be treated with the same medicines in 20 years time as we do now. You don´t develop resistance to these medicines as you do to antibiotics.

14.  Do you have any thing to add?

I think it is important to understand that innovation is not just product innovation. We need innovation in supply systems, in patient information, in public information and in regulatory systems. All these could have a profound effect on the treatment of people with common diseases. We should not only look at the innovation beyond the product focus, but also beyond the health system and the product, how do they relate? And if we look at biotech we should do this in relation to the health system.