Thursday, April 28, 2016

CERN Gives a Quantum Push to Open Science

In the biggest push towards Open Science so far, CERN launched its Open Data Portal with 300 terabyte dump of experimental data from real collision events of the Large Hadron Collider (LHC) openly available to all.
Through its Open Data Portal CERN has made available the experimental data in analysable form from the collision data of the first LHC run in 2010. Not just the data, CERN has made available the analytical tools too. The open source software to read and analyse the data together with the corresponding documentation in open access accompanies the data. CERN says that this data is meant for students and citizen scientists and expects that ‘these data will be of high value for the research community, and also be used for education purposes’.
Remember, we are dealing with data at the frontiers of complex scientific research. In an article CERN cautions that the complexity of this data from real collision events should not be underplayed. Those who access the data will have to put in time and effort to understand the data, the learning tools and the techniques to interpret the data.

Sharing of Real Experimental Data
Sharing of real experimental data has always been a highly debated issue. When should the data be shared? How will the credit be attributed to the data? How will access be regulated or should it be regulated at all? These questions had dampened the enthusiasm of well-meaning scientists and institutions that wanted to share data. To all these questions that troubled researchers for long, CERN has given an illustration of how experimental data can be shared, archived and preserved for long.
The Open Data Portal assigns digital object identifiers (DOIs) to the data sets and code, making them citable objects in the normal scientific communications, and offers the data openly for anyone to download since they are published under a Creative Commons license.
Another area of concern among researchers in sharing raw data was how to cite the data. LHC has addressed this concern with a clear data access policy for those who access the data. This contains its publication policy for those who analyse and publish papers by accessing the data. It requires a suitable acknowledgement and disclaimer to be included (in this case LHCb experimental data): 
“acknowledgement that the data was collected by LHCb, and disclaimer that no responsibility for the results is taken by the collaboration.
A suitable disclaimer is: This paper is based on data obtained by the LHCb experiment, but is analyzed independently, and has not been reviewed by the LHCb collaboration.”
This is second of such initiatives this year. Earlier this year, scientists from the Laser Interferometer Gravitational-Wave Observatory (LIGO) released data from the first confirmed measurement of gravitational waves and even included source code documenting the analysis step-by-step.

Pioneering Open Science
The LHC experiments at CERN are what one considers to be at the frontiers of research. It is heartening to see CERN adopting Open Science as a matter of conviction. Here is an excerpt from an article On the Road to Open Science written by Tim Smith who leads the collaboration and information services at CERN.
Science is predicated on the concept that the hypotheses that we propose to explain the phenomena that we observe can be tested through repeatable experiment. We should share sufficient details of our observations and conclusions for independent scrutiny, reproduction and verification. In this data-intensive age we have somewhat fallen short of this ideal since we have continued to “share” through publication processes which had no place for data, certainly not large volumes of it, nor the code that was needed to interpret it. Hence Open Science is striving to rebalance the processes and reintroduce data and code as first-class research objects to be shared, scrutinized and reused.

Even for Schools
The CERN Open Data Portal also provides real experiment data (event datasets from the ALICE,ATLASCMS and LHCb collaborations) specifically prepared for educational purposes for even high school students. These resources are accompanied by visualisation tools. Apparently over ten thousand high-school students are accessing, using and learning from this data every year. This data is meant for the international masterclasses in particle physics. For educational purposes the complex primary data has to be processed in a manner understandable as simple applications. CERN has developed many such applications and made them available online. In addition, it has invited, those who would like to build similar applications.

A Great Opportunity for India
This is indeed a golden opportunity for researchers and students in India. Indian researchers have been major collaborators in the CERN experiment. But these have been from specialised institutes. India has, at the same time, a large number of institutions teaching and doing research in physics and mathematics, with teachers and students of excellent calibre, but bogged down by outdated syllabus. They have now the ability to access and work on the live data from one of the most complex of the experiments ever carried out in physics. The teachers in these institutions who want to break away from the traditional mould has now tools that can excite brilliant minds to understand how complex problems in physics are addressed. School teachers have an excellent opportunity to ignite the interest of students in Physics.
Physics is seeing exciting times in leading Open Science movement. Indian researchers in physics and in other science disciplines should take an active part in this Open Science movement.

Sunday, April 3, 2016

Outcome Switching

Make my Trials!

A hot topic that is now being discussed in the scientific research is 'outcome switching'.  In layman’s language outcome switching means the authors of a study did not report something they set about to find they set out initially but included additional outcome without disclosing the result of the original findings, with no explanation for the change. The field is so new that there is no Wikipedia entry on this, yet!

The most discussed case in outcome switching is that of a clinical trial named ‘Study 329’. That study was sponsored by GlaxoSmithKline (GSK) on antidepressant paroxetine with tradename Paxil. The result that was published in 2001, claimed the demonstrated that the drug was well tolerated and effective as an antidepressant for kids. This way in which the result of this study has been published demonstrates what outcome switching is about. 
Study 329 of GSK set out to monitor the efficacy of Paxil as an antidepressant on eight specific parameters. On all these parameters the research showed that it had no significant impact; the drug was no better than the placebo sugar pill. The researchers then came up with additional 19 new measures. Just 4 of the 19 new parameters showed result. In the paper that was published the researchers presented the results on these four only without discussing the other components as if the study was set out to measure the impact of these four parameters only. So even though the pre-decided parameters showed negative outcomes these were not discussed in the publication and few additional parameters that suited the study got reported.

The above is not a rare incident. The Economist reported about a study published in BMC Medicine in 2015 which found that 31% of the clinical trials did not stick to their original parameters. The problem is beginning to receive academic attention. University of Oxford, has launched the COMPareProject. The  project aims to systematically check every trial published in the top five medical journals - the New England Journal of Medicine, the Journal of the American Medical Association, The Lancet, the Annals of Internal Medicine and British Medical Journal (BMJ). The finding so far are revealing. COMPare team has so far studied 67 trials (information in their site as on 3rd April). They found 9 trials conducted as per original protocol questions. In other cases, they found that 300 outcomes were not reported and 357 new outcomes were added.
GSK’s study 329 was initiated in 1992 and got completed in 1998. 

Fortunately, there has been changes in the regulatory processes after this. All trials have to be registered before they begin and the specified outcomes have to be published on website or similar national sites.

The website, retractionwatch carries an interview with Ben Goldcare the project leader of COMPare. He explains that not all changes in the outcomes of clinical trials are for nefarious reasons. What is of concern according to him is that when every time outcomes are switched, that creates a culture of permissiveness that lets other people do the same to tweak the trial’s conclusions.

The motivation for outcome switching can be many. Could it be mere survivorship bias? Survivorship bias is the logical error of concentrating on the people or things that "survived" some process and inadvertently overlooking those that did not because of their lack of visibility. This can lead to false conclusions in several different ways. But in clinical trials this can be very costly. But the evidence above weighs otherwise.

But the price may have been paid by patients. GSK's Paxil has been prescribed to millions of children and young adults. By early 2000s its sale was nearly US$ 2 billion a year!

You may read more about it in the Vox article or in the aptly titled article in The Economist - For My Next Trick

Wednesday, March 23, 2016

The (Unfinished) Conquest of Tuberculosis

World TB Day Thoughts, 2016

One more world TB day.

March 24, 1882 was when Dr Robert Koch announced at the University of Berlin's Institute of Hygiene that he had discovered the cause of tuberculosis (TB), the TB bacillus. In the second half of 19th century, TB was causing the death of one out of every seven people in the US and Europe. Koch's discovery opened the way to diagnosing TB and led to effective treatment. TB, dubbed as the ‘white plague’, declined substantially in the United States and Europe that by second half of 20th century sanatoriums were closed and routine screening was abandoned. The discovery of antibiotics led to such optimism that in 1964, S A Waksman wrote the book The Conquest of Tuberculosis.
Sadly, TB still rages in most part of the world, killing one person every 25 seconds. In India, two persons die every three minutes, even today. For most of the world, the conquest of TB is still a dream.
Experts are unanimous about the need of new TB drugs and diagnostics. So where do we stand now?
There has been some progress. Many challenges remain if we have to conquer the disease. 

The Good News

There has been progress in the drug discovery and development for TB. There are two drugs in advanced stages: Bedaquilin (Janssen Pharmaceuticals) and Delamanid (Otsuka Pharmaceuticals). The pipeline of TB drugs also looks promising with about 117 new candidates being reported by G Finder in its Survey as of October 2015.
On the diagnostic front, Xpert of Cephid is an excellent tool to detect drug resistance and where it is deployed, physicians are happy. DNA based diagnostics like Line Probe Assay are available.

The Challenging News

While the progress is significant, the sad news is that these are not translating to reduce the mortality in those parts of the world where it is most wanted, that too among the most vulnerable, poor in the tropics.
The reasons are known. Sadly, solutions are often found wanting.
The difficulty with TB is the absence of an attractive market. That acts as a disincentive. Most of the drugs in the pipeline has received support of public or philanthropic funds at some time, without which they would not have reached the stage where they are now. Some for profit companies have invested their funds as well. Pfizer and Astra Zeneca had developed a drug each. Both closed down their internal programs and have licensed the drugs out for development.
Added to this is the lack of effective diagnostics. Even after a century and a quarter of Koch’s discovery, most hospitals still use the method of sputum smear microscopy discovered by Robert Koch in 1882, to detect TB. It is a good test. But not capable of detecting drug resistance (DR). Thus people with DR get treated on the normal course leading to further complications.
Some of the following issues have already been discussed in this blog earlier
  1. Both Janssen (for Bedaquilin) and Otsuka (for Delamanid) are seeking marketing approval in limited number of countries and not in all TB affected countries
  2. The above drugs have affordability concerns.
  3. The diagnostic tools are not widely available and where available it has raised affordability question.
  4.  Trials of TB are complex and time consuming. Yet, no urgency is shown by any of the agencies to get trials of the available drugs done at the earliest.
  5. The new diagnostics have affordability concerns. 

The Missing Million

It is reported that the Joint Monitoring Mission of the RNTCP has admited that in the last two years, more than a million people living with TB in the country have gone undiagnosed or unreported. This fact has been known and has been called the missing million. Addressing this missing million is a huge challenge.
India has recently approved the use of Bedaquiline for MDR TB treatment. It has been hailed as a wonder drug for TB. While there is no doubt about the efficacy of this new drug, the tags like wonder drug could only help to bring in complacency back into the system. Take a note at the caution that WHO has added in its guidelines for the use of Bedaquiline:
Bedaquiline has been reported to disturb the function of the heart and liver in particular. Interactions with other drugs, especially lopinavir and efavirenz (used in the treatment of HIV), ketoconazole, as well as other drugs used in the treatment of MDR-TB (eg moxifloxacin, clofazimine) may be expected. More deaths were reported among patients taking bedaquiline during the studies carried out to investigate the drug, although it is not clear whether this was due to the drug. For all these reasons, it is important that patients are closely monitored and that adverse events are systematically reported (“active pharmacovigilance”), particularly those that are serious and life-threatening…

There is no room for complacency. TB needs new drugs. 

The Development Bottleneck

Globally, it is sad to note that even in the background of the robust pipeline that has been built up over the past two decades has seen little progress in the drug development front. There are 117 new compounds on the pipeline. The public funds have promoted research but not development, it is now time to shift our focus from discovery to development front. If concerted efforts are made several new drugs can be got to the market in a decade’s time. But that requires determination and concerted action which, unfortunately, is absent as of now.

The IP Bottleneck
It is difficult to believe that patents do play a role in limiting the development of new TB drugs. But even that is happening. The reason is that all drugs in pipeline are under patents. So no one other than the patentee/licensee could develop the drugs. And it is left to the will of the patentee/licensee to develop at their pace for the markets which they want.
The need of new TB drugs is global, a clear and present requirement. Therefore, is it inappropriate to leave it to some companies to develop and market the drugs in markets of its choice and leave the patients in other countries to their fate.
If we really have to conquer TB, the world has to give a real push at the development front. The business as usual approach of leaving everything to the market has not worked and will not work in future too. Someone will have to take the yoke on her shoulders and get the drugs through the development phase through a real push.

Needed : A New Innovation Policy in Market Failure Cases
 The post-industrial society has an IP based innovation policy as the primary mechanism to foster innovation, which is driven by markets. This is clearly not working for neglected diseases. In market failure situations like TB, the world does not know how to innovate affordable products accessible to all. We need to innovate the way we innovate in market failure cases.

Monday, February 15, 2016

Ending TB Epidemic – An Unreachable Milestone in Sustainable Development Goals?

Is it possible to end the epidemic of TB in the next 14 years as contemplated in the Sustainable Development Goals? Simple answer is a straight no!
The world is justifiably happy that the Millennium Development Goals (MDG)on TB of arresting and reversing the TB mortality trend has been achieved.  TB mortality has fallen 47% since 1990. This reduction by half is a significant achievement made possible by the enthusiastic implementation of DOTS and WHO and national governments deserve credit.
The Goal 3 of the Sustainable Development Goals (SDG) calls to end the epidemics of AIDS, tuberculosis, malaria and neglected tropical diseases by 2030 and combat hepatitis, water-borne diseases and other communicable diseases.
Achieving SDG targets will require management of the complex drug resistance (DR) problem in TB, particularly in high incidence countries like India.  
Why is it tough
The Global Tuberculosis Report 2015, reported 6 million cases of TB globally in 2014. It is estimated that around 3,00,000 had multi drug- resistant (MDR TB) while only 1,23,000 were detected. 1,90,000 people died of MDR TB. Globally, only 50% of MDR cases get successfully treated. More than half of the global DR TB cases are in India, China and Russian Federation.
As per WHO estimates, the cost per patient treated for drug-susceptible TB in 2014 ranged from US$ 100−500 in most countries. This is mostly met by public health system through DOTS, supported by Global Fund. The cost per patient treated for MDRTB was typically US$ 5000-10,000. The MDR TB costs almost 10 times and does impact national TB budgets significantly. If the large number of undetected MDR TB cases come up for treatment, even at the current costs there will be a significant burden on national TB control budgets. There are limitations on the reach of public facilities and many patients avail private care which is paid out of pocket. That is why there are serious concerns about the cost of new TB drugs.
Experts are unanimous that new drugs are needed to manage drug resistance.
Happily, there are new drugs are on the horizon. FDA has approved Janssen Pharmaceutical’s Bedaquiline (tradename Sirturo), based on Phase IIb results. Its Phase III trials are ongoing. Similarly, Otsuka Pharmaceutical’s Delamanid has also been approved by EMA based on Phase IIb results; its Phase III trials are still ongoing. TB Alliance is testing PA 824 in combination with other drugs. There are other candidates like, Sutezolid, a drug developed by Pfizer, now licensed to Sequella and AZD 5840 of Astra Zenecca.
Yet, there are serious concerns of affordability and accessibility of the new drugs. This is due to the particular nature of TB. TB has earned the sobriquet ‘poor man’s disease’, and is prevalent in the less fortunate neighborhoods in the tropics.
The Cost of the New Drugs
Janssen has priced the Sirturo (Bedaquiline) at $ 30,000 in US for the course of treatment. Delamanid of Otsuka is marketed in EU under the tradename Deltyba in Europe and is priced at around US $ 30,000 (Delamanid costs £1,045.83 in UK and €1,500 in Germany, for a course).
The new standard of price seems to be USD 30,000. Janssen is offering the drug at a discounted price of $ 3000 in middle income countries and $ 900 in low income countries.
Even with the discounted price of $ 3000, if we add this price to the WHO’s lower estimate of the current cost of $ 5000, a course of MDR TB treatment with the addition of new drugs could cost around $ 8000. So the MDR TB regimen is likely to cost around Rs 5,00,000 or more in India.
This likely cost of MDR TB regimen would be beyond the means of a large number of TB patients. A comparison could be with the Income Tax payment threshold amount in India. India has a threshold limit of Rs 2,00,000 (~$3000) above which all are required to pay income tax and file returns. As per news reports, only 35 million tax payers (3.5 crore) have income above this limite and pay Income tax, which is just 3% of Indian population. Even in this bracket, the majority of the tax payers fall in the category of Rs 2,50,000 to Rs 5,00,000 bracket
As per the last census, the average household size in India is 4.8. Most of these households may have only one breadwinner. That adds to the financial strains of healthcare. The healthcare costs in India is largely borne by the patients with about 70% out of pocket expense (as compared to less than 30% in developed world). With most of the affected population being poor, the way the new drugs are being priced, MDR TB treatment will be priced out of reach of most of the affected population in the most affected countries.
Affordability is only one part. There is also a more serious concern of access to the new drugs.
Accessibility Issues
Both Bedaquiline and Sirturo are available only to patients in US and Europe, that too in limited numbers. It is reported that by March 2015, only around 1000 patients have received Bedaquiline. The results of the Phase III trials approved in 2013 is yet awaited; an indication of the length and complexity of TB clinical trials. Even if the trials are successful, Janssen has registered the drug only in 21 countries. Otsuka has moved for registration only in Europe, Japan and South Korea. WHO has issued guidelines on the use of Bedaquiline and Delamanid, but the limited access keeps the drugs away from the patients in a large number of countries.  
There is little progress in the case of Sutezolid, which remained dormant in the hands of Pfizer for a long time before Sequalla got the license. Sequalla has not yet announced any plans for trials in the developing world.
On their own the pharmaceutical companies are not interested in venturing into the developing world, as markets TB drugs are not attractive enough.
Affordable Diagnostics
DR TB cannot be tackled detecting it at the earliest. This requires better diagnostics tools that detect resistance which enables the physicians to prescribe the right therapy. The new diagnostics like Xpert are expensive and require frequent purchase of costly cartridges. What is required is an affordable high quality diagnostic tool.  
Concerted Steps Needed
The above background points to the need of concerted action by health policy makers to get new drugs for TB to the patients in the high burden countries. There has to be a global effort to push the clinical trials of all drugs in pipeline in the developing world where the disease is predominant. Conduct of clinical trials will require access to funds and facilities to conduct complex TB trials. The regulatory authorities in high burden countries will have to be equipped to take up registration of new TB drugs on priority. WHO and global civil society and patient groups will have to push for such measures. Unless such steps are taken WHO’s issuance of guidelines for Bedaquiline and Delamanid would only be of academic interest and useless for a majority of the afflicted. A promising candidate which is progressing in trials is PA 824 of TB Alliance which is undergoing trials in combination with other drugs. In line with its mandate TB Alliance is likely to make the drug affordable and accessible.
No such new initiatives are visible, at least in India which harbours one fourth of global TB burden. We seem to be content with the slow progress of DOTS. 
At the rate, we are going, the SDG goals are unlikely to be met, as the deadline is just 14 years away. Without globally coordinated measures to make affordable new drugs available we will still be grappling with the TB epidemic in 2030 and, Goal 3 of SDG will remain elusive for most nations.
The twinning of hope and the despair on the TB drug-discovery horizon reminds one of Charles Dickens:
It was the best of times, it was the worst of times, it was the age of wisdom, it was the age of foolishness, it was the epoch of belief, it was the epoch of incredulity, it was the season of Light, it was the season of Darkness, it was the spring of hope, it was the winter of despair, we had everything before us, we had nothing before us, we were all going direct to Heaven, we were all going direct the other way - in short, the period was so far like the present period…

Sunday, August 30, 2015

Why are Indian R&D Centers Closing Down?

Are the top tier private R&D organisations in India closing down their operations? Just look at the following data compiled by Biospectrum in its August 2015 issue 
  • In January 2014, AstraZeneca announced the shutting down of its drug R&D unit, dedicated for neglected diseases, one of its kind, located in Bangalore.  
  • In August 2014, Indian healthcare giant Piramal announced its decision to shut its Mumbai R&D unit.
  • In 2015 Pfizer's Thane plant is shutting down its operations.
  • Sandoz is shutting down its Turbhe R&D site in Maharashtra
  • Merck has announced shutting down of its Bangalore Genei facility, recently.
Those who are familiar with the South Indian way of speaking English would have heard this expression – "what is happening, I say?!" (in typical south Indian fashion, ‘say’ pronounced with an elongation). That’s the question that comes to one’s mind as R&D centers shut down one by one. 
To set the record straight, Pfizer’s Thane plant was a manufacturing facility. Same is the case with Sandoz Thurbe plant which was manufacturing APIs. Others are all R&D units. This does not digress from the fact of R&D closures - Biospectrum has brought out an important issue. 
It is tempting to see these closing downs as random business operation and go on with business as usual. The numbers are far too many to lose sight of its significance. The R&D units that are being shut down are in pharmaceutical sector, a key driver of innovation. In pharmaceutical sector, it is R&D which determines the standing in the pecking order. As I discuss below, it might have repercussions in other areas. 
Way back in 2004, noted columnist Swaminathan S. Anklesaria Aiyar (Swaminomics), in his column in The Times of India, titled ‘R&D: India’s New Star Industry’, had pointed out the emergence of R&D industry in India. During the license permit raj there was no incentive to do R&D, he argued. The competition brought in by economic liberalisation in the 1990s made R&D is an essential tool to compete and survive. He warned the Americans who complain about call centers that they had not seen anything yet, as biggest American companies were setting up R&D centers in India; citing examples of setting up of R&D centers by General Electric, Microsoft, IBM, Cisco, Intel, General Motors, Astra Zeneca, Motorola , Texas Instruments. He predicted an R&D revolution in India and hoped with many other Indians for blooming of Indian R&D.
A decade later, it looks like Swaminomics has had to eat his words. Instead of bloom, we are witnessing a withering; we are witnessing a slow retreat by those who set up their R&D centers. And at the same time, some of Indian R&D companies are going abroad to set up their research facilities. Glenmark has set up an R&D center in Switzerland. This is a reason for worry about anyone who is interested in R&D and innovation in India.
In India, prior to the wave of MNC R&D centers cited above by Swaminathan S. Anklesaria Aiyar, R&D was done mainly in the public sector laboratories. The traditional Indian public policy approach on R&D was to create a golden handshake of public sector laboratories and private enterprises. Public sector labs were established to support R&D in the industry. In 1944, the then Government released ₹10 million (US$150,966) to set up National Physical Laboratory, National Chemical Laboratory and National Metallurgical Laboratory (NML). The stated objective was to develop industry in pre-independent India, and also to incentivize private firms to support industrial research. It worked; the objective was met. The Tata Trust promised to donate ₹1.17 million (US$18,000) to NML.  The government in its turn located NML at Jamshedpur, where Tata Steel is located. For many decades, and even now, NML provide world class R&D support to Tata Steel located at Jamshedpur. Two other laboratories Central Mining Research Institute(CMRI)  and Central Fuel Research Institute (CFRI), were set up to provide basic research, R & D back up, advisory services and help in technology upgradation and adaptation to coal and mineral based industries to reach the targeted production with high standards of safety, economy and cleaner environment. These two labs were later merged to create Central Institute of Mining and Fuel Research (CSIR-CIMFR). CSIR’s chemical laboratories have been the backbone of India’s generic industry and it has been acknowledged widely
The setting up of private sector R&D by MNC majors as pointed out by Swaminathan Ankaleseria Ayer was a qualitative shift, which acknowledged the research capability available in the country which could give competitive advantage to MNCs, globally. He wrote: “The biggest American companies are now setting up R&D centres in India. They are not coming for cheap labour in sweatshops. They are coming for India’s brains.” Indian education system had produced quality human resources who could produce world class R&D for MNCs. From a public sector dominated R&D, India was moving to private sector R&D, which, it was hoped would drive innovation and growth. This shift is getting reversed with dangerous portents. 
Those who are familiar with R&D and innovation knows very well that both innovation and R&D thrives within the surrounding ecosystem. The early movers into R&D centers have therefore taken extra pains to set up the ecosystem around them. For example, the Astra Zeneca research center at Bangalore created a drug discovery ecosystem around it. It was benefited by the scientific innovation ecosystem created by the Indian Institute of Science. This ecosystem enabled creation of Contract Research Organisations who do contract R&D for global majors. Shutting down of the research centers decimates the ecosystem that got developed. Repeated shutting down as Biospectrum has pointed out might irreversibly damage the ecosystem built up assiduously, with great effort.
How challenging is it to set up a new R&D center in India? If experience of some passionate ex scientists of Astra Zeneca is anything to go by, it is an uphill task, choked by bureaucratic stranglehold. Dr R K Shandil, Dr Sridhar Narayanan were with Astra Zeneca facility which was shut down. Passionate about discovering new drugs for neglected diseases, they founded a Foundation for Neglected Diseases Research, along with P Gopal Krishnan, a Chartered Accountant. After almost a year of its setting up, they are still running from pillar to post to get the approvals required to set up an R&D unit, a drug research facility for tropical infectious diseases which predominantly affect India. Will we ever learn to make it easy for people to do business, even if our Prime Minister himself wants it? Luckily scientists are optimists and they are still at it. But when decisions are taken on business considerations by MNCs, luck plays very limited role.
The Prime Minister of India gives considerable importance to developing manufacturing facilities in India which will create jobs, through his 'Make in India' campaign. Make in India requires extensive R&D. The shutting down of R&D centers does not augur well for the make in India campaign. Policy makers need to realise this.
The much acclaimed human resources (‘brain power’ and research capability) still exists in the country. Indian minds are driving innovation in many parts of the world. Then, why are these R&D centers are shutting down? The reasons have to be systemic, and goes far beyond the availability of skilled human resources. These reasons are definitely large enough to obfuscate the human resource and cost advantage that India enjoys. Our policy makers need to find the real reasons and take quick corrective measures.

Thursday, August 13, 2015

The Economist Decries Patent System

The Economist, one of the most reputed journals, has raised a red flag on the patent system, with a cover story titled ‘Set Innovation Free: Time to Fix the Patent System’ in its August 8th to 14th, 2015 issue. Its Editorial titled ‘Innovation: Time to Fix Patents’ states: "Today’s patent regime operates in the name of progress. Instead it sets innovation back. Time to fix it."

The issue carries an Editorial (called leader in The Economist parlance) and a detailed 3 page article titled ‘Intellectual Property: A Question of Utility’. The main arguments put forward against the patent system is summarized below:

i.                    Evidence show that stronger patent system do not necessarily promote innovation. In a surprising twist to the narrative, more akin to the lingua of a civil society organization, The Economist goes back to the history and recall that the industrial revolution that led to steam ships to the railroads did not have patents as we know today.  It also recall that it argued against patents in the 19th century.

ii.                  The policy premise supporting patents is they serve public good. It provides an incentive to innovate and publish the new idea, in return of a material gain. Publication of new ideas spread the technological advancement as one innovation builds on another. The Economist argues that the evidence to support this claim is weak. Patent documents are carefully written by experts to obscure how it works even from the experts in the field. Instead of spreading knowledge, the current patent system has created a parasitic ecology of trolls and defensive patent holders, who aim to block innovation to grab a share of the spoils than to promote innovation.

iii.                A growing body of research including a 2004 study by the National Academy of Sciences led to the conclusion that the society as a whole might be better off with no patents, with a few exceptions, such as medicines.

iv.               The patent system is expensive and increases costs on the consumers. The cost of challenging a patent thorough legal process is high.

v.                 The cost of innovation that never takes place because of the flawed patent system is incalculable.

vi.               The article rely extensively on a book ‘The Case Against Patents’ by two economists Michele Boldrin and David Levine, compiling the research done so far, arguing that patents are neither good at rewarding innovation nor help in real spread of technology. After analyzing 23 studies carried out in the 20th century on the patent system, they found “weak or no evidence that strengthening of patent regimes increases innovation”.  All it does is to get more patents filed, which is not the same thing as innovation. The main arguments of the book are summarized in the article as below:

a.     Evidence suggest that 19th century countries that lacked patent systems were no less innovative than those which had them.

b.     An exception to the general finding only goes to prove the rule proposed that patents per se do not promote innovation. The exception is the case of Taiwan’s 1986 patent reforms. After the reforms that strengthened Taiwan’s patent system, the R&D spending in the country went up and more American patents were granted to Taiwanese nationals. The article argues that this evidence show only that the countries with weaker patent protection can divert investment and R&D spending to their territories by strengthening it. It does not demonstrate any increase in worldwide R&D spending or innovation.  

c.      Expansion of patent system do not bring about more innovation as evidenced from US experience. In 1970, US extended patent protection to sexually reproducing plants. Studies on wheat showed that this measure did not lead to greater research spending or increase in yield. Even after extending patent protection to all biotech products in the 1980’s, the productivity of agriculture in US rose only at the same rate as before.

d.     The rate of innovation show little relation to patents. In industries from chemicals to computer software, waves of innovation began with lots of participants. Patents started to get filed only years later, once the spurt of innovation die down the incumbents in the maturing industry seek to exclude new entrants as well as to protect themselves from their rivals law suits. The real cause of patents is competition and is only a result of innovation and not the cause of it. The patent system is good for incumbents for fending off competition and not in public interest of promoting innovation.

e.     The system may be offering benefits to some start-ups with little access to capital but having new ideas but not s in mature industries like aerospace and car making. In such industries, the patent on technologies is only one of the component of creating a world beating innovative product. The article cites the cases of market leadership of BMW and Boeing which Chinese companies are unable to crack.

f.       In some sectors like the pharmaceuticals, the argument for continuation of patent is strong due to high initial cost. Here also, evidence do not stand up to the claim of patents fostering innovation. Till 1967 German companies could only have process patents. But they produced more innovation than the British ones which enjoyed product patents.

vii.            The Economist argues for a top to bottom reexamination of whether patents and other forms of intellectual property protection do their job and whether they deserve to exist.  It notes that outright abolition proposals may create issues in terms of ethics of property rights. It points out that no property rights are absolute, citing examples of demolishing houses to make way for roads, taking money through taxation, and putting controls on land use. In these cases a balance is struck between claim of the individual and that of the society.  It says that with ideas, the argument that the government should force the owners is strong.

viii.           The Economist put the argument of free riding upside down.  Free riding problem on ideas is the strongest argument for providing property rights, because the imitator can reproduce the idea, once created, without investment. It says sharing will lead to extra innovation. Ideas overlap and innovations depend on earlier advances, for example, there will be no Iphone without touchscreen. The signs are that innovation today is less about entirely novel breakthroughs but more about clever combinations and extension of existing ideas. Therefore free riding has value in fostering innovation. Open source software including the Android operating system are clear examples.

Suggestions for Reforming Patent System:

The Economist cautions the reformists that they should be aware of their own limitations.  As innovation is complex. At the same breath it points out that the current regime is susceptible to lobbying and plea of special interests.   A ‘clear and rough and ready patent system is better than a complex and an elegant one. In government as in invention, simplicity is strength (Highly desirable but easier said than done as anyone involved in policy making knows. Anyone other than Economist saying this would have been dragged down and beaten up).

The Economist gives the following suggestion for reform:

i.                    The patents should come with a “use it or lose it” rule, so that they expire if the invention is not brought to market.

ii.                  Patents should be easier to challenge without the expense of a full blown court case.

iii.                The burden of proof for overturning a patent in a court should be lowered.

iv.               The requirement that ideas should be non-obvious should be strengthened. Economists states that Apple should not be granted patents for rectangular tablets with rounded corners and nor Twitter the patent on ‘pull to refresh’.

v.                 Governments should gradually reduce the term of patent protection. 20 year is a long term for patent. In fast moving industries, governments should gradually bring down the length of patent. The Economist argues that even the pharmaceutical firms could live with shorter patents if the regulatory regime gives faster approvals.

vi.               Experiments with other forms of financing innovation should could be run alongside the patent system. It beseeches the defenders of the Patent system to do so in their own backyard.


What the Economist did not say:

One is disappointed that a critique as comprehensive as what The Economist has done has left out one of the main challenge in driving innovation for large populations. Patents drive innovation only in those areas where market forces are active. It fails to drive innovation in market failure situations. Take the example of neglected tropical infectious diseases which affect vast segments of population in the tropics. These tropical infectious diseases are called neglected because the pharmaceutical industry which drives innovation does not see profits in them. It is a clear example of incalculable cost of innovation that never takes place due to the patent system. The patent system is inequitable in itself. Some suggestions proposed by The Economist, like different modes of financing innovation could address this. There are working examples of product development partnerships in neglected diseases like TB Alliance and MMV, DnDi, Gavi and many others which goes on to show that an alternative system of financing innovation exist in areas where patents do not work.

Compulsory License

The Economist argues that property rights are not absolute. The state can place restrictions on property rights in public interest. There are extensive arguments about wide sharing of ideas and governments have recognized the limits on the patent system. Yet, it shy away from mentioning about the TRIPS recognized too of compulsory license in public interest. To be fair, there is an indirect reference to compulsory license while discussing the US Federal Trade Commission’s recommendation to President Franklin Roosevelt to replace patent system with compulsory licensing.

How can any article which discusses the thereat to innovation posed by the patent system and list out some outlandish (and some not so outlandish) solutions not even discuss this tool available in the existing law? 


The Economist has not said anything really new or path breaking. What has been listed are well known issues and the solutions are also known ones.  

The difference is only this – The Economist, the champion, mouthpiece and lead advocate of free market capitalism is saying this. One can only hope that the world sits up and notice.

Saturday, August 1, 2015

The Curious Copyright Case of Happy Birthday Song

You might find it hard to believe, the ubiquitous Happy Birthday song which we sing in all birthdays is claimed to be under copyright protection, which earns Warner Music a licensing royalty of about $2 Million per year.

A dispute that is ongoing in a New York Court is unraveling its interesting story.

The claim of original creation of "Happy Birthday" song is with two sisters from Kentucky, US, Mildred Jane Hill and Patty Smith Hill who were Kindergarten teachers. Mildred, born in 1859, was a concert pianist and composer. They composed a song of greeting for the children and Mildred came up with the melody (which we now know as the tune of "Happy Birthday") for teachers to use in welcoming students to the class each day:
Good morning to you,
Good morning to you,
Good morning, dear children,
Good morning to all.

During the 19th century, birthday celebrations as we know it today were not so popular. To quote from Prof Brauneis’ essay (aptly titled 'Copyright and the World's Most Popular Song'):
According to scholar Elizabeth Pleck, birthday parties did not become common even among wealthy Americans until the late 1830s; modern birthday cakes emerged after 1850; and peer-culture birthday parties, involving children of the same age as the child whose birthday was being celebrated, emerged between 1870 and 1920, after American urban public schools became age-graded.
The history of how “Good morning to you” song turned into “Happy Birthday to you” is unclear and that adds o the intrigue of the ongoing copyright dispute. No one knows who wrote the words to "Happy Birthday to You" and put them to Mildred Hill's melody, or when it happened. The lyrics to "Happy Birthday to You" began appearing in conjunction with the "Good Morning to All". One of the earliest known book to include that combination of lyrics and melody is The Beginners' Book of Songs, published by the Cable Company in 1912.

A Broadway musical called Thousand Cheers used Happy Birthday version of Good Morning to you without the Good Morning to you part. The Hill sisters sued the producers for copyright infringement of their song claiming $250, at that time. This lawsuit was apparently settled. It was the Thousand Cheer show which was immensely popular which made the song a household ritual in all birthday parties. Time reports that the song and the practice of organizing birthday parties emerged around the same time, in the beginning of 20th century – ‘the song and the occasion to sing it came up together’. “Happy Birthday to You” became the standard birthday song in the period between 1915 and 1935. A statement of the American Society of Composers, Authors and Publishers (ASCAP) in 1999 claimed that “Happy Birthday to You” was the most popular song of the twentieth century.

In 1935, a music publisher Clayton F. Summy Company, published "Happy Birthday (to You)" with the authorization of Jessica Hill in 1935 and filed copyright registrations for several versions of the song. This company which owns the copyright changed hands and is currently owned by Warner Music Group which collects about $ 2 Million in royalties per year. 

The song could claim to still remain in copyright domain due to peculiarities of the US copyright law. Under the laws in effect at the time of publication copyright would have expired after one 28-year term and a renewal of similar length, falling into public domain by 1991. However, the Copyright Act of 1976 extended the term of copyright protection to 75 years from date of publication, and the Copyright Term Extension Act of 1998 added another 20 years, so under current law the copyright protection of "Happy Birthday to You" will remain intact until at least 2030.

In June 2013, a film company working on a documentary about "Happy Birthday to You" filed a class action lawsuit to invalidate Warner Musics claim to copyright ownership of the song. It is this case that is making news. The New York Times reported that Lawyers for a filmmaker in New York said they had discovered “smoking-gun” evidence that the song “Happy Birthday to You” should no longer be subject to copyright restrictions. The court filing argues that copyright law at the time required the work to exhibit a copyright notice to claim copyright protection. This was not found in a 1922 publication without which the work was “interjected irrevocably into the public domain”. The following image has been produced in the court to substantiate this claim as reported by Techdirt.  

The actions of Warner Music, it is claimed, was to deliberately suppress the above evidence. We have to wait to hear what the court has to say on this matter. 

So do you have to worry if you sing Happy Birthday song in India? 
No, not at all. The song is in public domain in India due to an interesting provision of copyright law.  Though Copyright enjoys international protection, the duration of copyright, comes under the national treatment principle. In India, the copyright term is till 60 years from the year of publication. The Happy Birthday song which was published in 1912 is clearly outside copyright domain in India. 

However, in the United States Warner Music asserts copyright and till a court invalidates this claim of copyright ownership, the song "Happy Birthday to You" remains in a copyright-protected state! But as per the evidence that are being placed before the court, the US$ 2 Million that Warner Music earns seems to be without legal basis.

This is a clear case of Copyright overreach. It is such behavior that puts the entire system to disrepute in the eyes of the law abiding common-folk.