Challenging times for the Indian clinical research industry: Coping with adversity.

One is tempted to think that tighter controls and stringency of law will result in weeding out situations that result in human or material harm. When cases of deaths in clinical trials and compensation came to the front pages of news papers, similar sentiments were expressed by the polity and the media. An entirely new regime was put in place rapidly to correct all ills ailing the conduct of clinical trials in India.Will this suffice to protect the rights, safety and well being of Indian clinical trial participants? Will there be no coercion, exploitation or malpractice as has been suggested in some quarters? The question to ask is, do more laws or increasing the stringency produce more compliance. Let’s look at the case of building laws in India. One might argue that it doesn't compare to clinical trials where human life is involved. However, a closer look at construction and building requirements will make us realize their effect on human life and more importantly the environment.

A recent media report compared building bye laws and approval requirements between India, Hong Kong and Singapore.In Hong Kong there are 6 approvals required and these take on an average 2 months and 7 days. Singapore has 11 approval requirements which take 26 days on an average. In contrast in India 34 approvals are to be put in place for a housing project. These take 6 months and 16 days on an average.

So, are our big cities like Delhi, Mumbai and Bangalore any better than Singapore or Hong Kong? Is the construction more robust, are there no mishaps and is our environment better than these countries that have lesser approvals or less cumbersome processes.

The Clinical trial environment is a much regulated one. The industry has a universal preamble- to safeguard the rights, safety and well being of human participants. Every trial should have a sound scientific basis. The benefits should outweigh the risks for any research. No study procedure should be conducted unless an informed consent is given by the participant on their own free will. Every law and guideline governing the industry has these tenets enshrined in bold. Every stake holder swears by these requirements. In India there are at least 3 guidelines, ICH GCP (international), ICMR and Indian GCP that serve as a road map that must be followed. Compliance to these is mandated in the Indian Drug and Cosmetics act, specially the Schedule Y. Over and above if the trial is for registration in other GCP regions then Indian stakeholders have to be compliant to these regions legal requirements as well. (Eg. 21CFR of the US FDA or Directives of the EMA).  These laws also make it mandatory for periodic review of the conduct of trials by independent quality control and assurance personnel. Every step, person, task and stakeholder in clinical trials is required by law to comply. There are standard operating procedures that set the boundaries in which clinical trials have to be conducted. In an already regulated environment, merely bringing in more bureaucratic controls will not help mitigate the risks highlighted by various NGO’s or the press.

We have road safety laws. Everyone knows how important it is to use helmets while riding two wheeler s  We have red lights, pedestrian crossings, subways, over bridges and fines for over speeding. Yet everyday there are reports of road traffic accidents or pedestrians being overrun. One might argue that these are a result of lack of application of laws, corruption or lenient fines. These are the same arguments that are being used to tighten controls in clinical trials.

Will modifying cars that do not allow speed over 10 km per hour or disallowing people from walking reduce accidents. In other words you cannot have regulations that strike at the very basis of processes. To travel you need vehicles that can drive at different speeds, people will need to walk to different points. Similarly clinical research has scientific basics that cannot be interfered with by regulations. An example of this dangerous trend is seen in the recently implemented rules. If there is no benefit from an investigational product the participant has to be compensated. While framing this rule, some one just forgot that one of the major purposes of conducting a trial is to see if an investigational product produces any effect. It is like asking people not to walk and stay indoors.

Why have clinical trials in India at all? India survived without them till 2005. There was no dearth of medicines. Is the ‘Innovation’ tag enough to support the continuance of trials in India.  To understand this one has to look at why clinical research is needed. No medical management today is even near perfection. There are various safety issues with even simplest of drugs like paracetamol or aspirin. In many diseases even after seeing the best doctors and having the best management, patients continue to suffer. It is this suffering or unmet need that clinical research hopes to fill one day- the need for better and safer medicines. Some will argue that why subject Indians to the un-certainties of research, when owing to its market size, pharma companies will eventually come around to sell their products. This is unethical. The populations that benefit from research should share the burdens of research as well. 

Moreover medicine is progressing towards biological, gene based therapies and personalized medicines. If India doesn't participate we will never know if a particular medicine behaves abnormally in Indians. It may be too late when the medicine has been used by millions after coming directly to the Indian market, without scientifically sound clinical trials.

There is enough data (again obtained from research) to show that participants in clinical trials benefit by merely being part of the study. These benefits are especially in terms of greater information on the disease and its management resulting in better self care. The Investigators who conduct these studies interact with their global counterparts; get a better feel of international guidelines & recommendations on disease management. This translates into better clinical practices even for the routine non study patients.

Then there are the economics of the matter. Even though the bio-services space may be much smaller than other industries like IT or banking it still is one of the only remaining growth stories in the Indian economy. Market estimates put a 12-15% growth rate for bio-services. This is in comparison to the single digit growths being recorded by most industries in India. According to recent estimates the bio-services industry generated revenues around US $ 750 million in 2011-12, despite suffering a 20-30% decrease in growth from previous years owing to the uncertainties in the regulatory environment. World over there is a movement by governments to foster innovation and science. Biotechnology, and pharmaceuticals are important for humans as they help us achieve health.  Future economies of countries will depend on ownership's and participation in these innovations. Putting in place regulations that drive the innovators away will harm India in the long run.

What remains to be seen is how the bio-services industry copes with this adversity. Many industries have faced similar predicaments and come out with better coordination and measures. Take the recent case of the tourism industry that was hit by the series of rapes that happened in 2012-13. The sequence of events started with the brutal Delhi gang rape in Dec 2012. Then in early 2013 there were reports of tourists being raped. According to press reports, Associated Chambers of Commerce & Industry of India estimated a 25 % fall in tourist inflow into India. The female tourist flow was severely affected.The industry reacted by trying to bring in a sense of assurance that they would take greater security measures. There were whole floors devoted to female travelers who were coming to India alone, all female staff to manage hotel check-ins and housekeeping of floors. Greater regulation and checking of the travel services availed by female tourists were some of the measures that the industry undertook.

Another case to look at is the BPO industry and its reaction to cases of credit card fraud. At the height of the BPO boom, Indian firms were hit my numerous scandals involving fraud and theft of sensitive data, especially involving bank or credit card details. The Indian Information Technology Act, 2000 was considered inadequate. Indian laws did not treat this as a criminal offence, even if the data theft was proved. There were even cases where foreign media houses ran sting operations and then published these sensationalizing the issue.

Similar media exposure has happened for clinical trials in India. Some of these have been widely publicized the world over. These have then been used to paint the entire clinical research field in India as being the black sheep. Rather than fostering a healthy debate, all this misguided media exposure has led to, ad hoc mechanisms being put in place without any careful thought to implementation. How can an already overburdened regulator cope with more paper work and regulations to apply? The government has to seriously look at the infrastructure required to sustain the new processes not only in terms of numbers but also in terms of experienced people manning the posts.

The BPO industry responded to this onslaught by self regulation and taking measures to clean its own house with the help of industry body NASSCOM.

How the CRO and pharmaceutical industry finds its way out of this mess still remains to be seen. Will the industry survive this deadly blow to its credentials?

What will really help is self regulation & discipline. Not that this does not exist at present in clinical trials. As stated earlier, clinical trials are conducted in one of the most regulated systems existing. Greater diligence and coordination between stakeholders is required. Efforts have to be made to share information and devise mechanisms to prevent the rights, safety and well being of participants from being violated. The industry has to be upright in providing compensation where it is due and required on a case to case basis.

The greatest measure has to be in the form of sensitization of the general public, media, political class and bureaucracy of the finer nuances of clinical research. This will require greater interaction, public debates and campaigns. The public has to be assured that the human participant’s rights will be safeguarded. This has to be put in practice not only in words but in actions.

The regulator and the government have to be informed about the dangers of some of the rules put in place. Many of these could be counterproductive and in-fact may introduce malpractices in public. Any cancer patient who is sick could be enrolled in a study with a hidden motive of availing the benefit of the compensation clauses being put in place without adequate safety measures.

The industry will also have to work with the regulator to work out the implementation of some of the new requirements and help them assess the impact. The Indian regulator mandated on 08 Feb 2013 the registration of ethics committees (ECs') in India. Only registered ECs’ can review and approve protocols. This is a very important and good move to weed out non committed players from the field. The regulator moved swiftly to invite applications (by 25 Mar 2013). It earnestly started examination of all applications from ECs’ throughout India. The first list of approved EC’s was released on 1 April 2013. This shows the seriousness and pro-activeness of the regulator.  However a look at the list of approved ECs’ shows that at least in the initial approvals, only institutional ECs’ are being approved. What happens to Independent ECs’ is not clear at the moment? Currently there will be a significant proportion of independent ECs’ that are providing oversight to sites in already running protocols. What happens if an amendment has to be moved in one of these studies involving independent ECs’? There are many experienced investigators that work with Independent ECs’, will their experience be lost as they can no longer participate due to the lack of an institutional EC? Moreover what happens to those independent ECs’ that have a vast experience and robust system in place? Will we lose out on their expertise? The industry will have to approach the regulator to work out a mechanism for these scenarios. The industry could look at an accreditation system for independent ECs’. They can then approach the regulator to register the accredited ECs’. This will both place an independent safeguard and provide an assurance of standards.  One such accreditation could be the Association of Accreditation of Human Research Protection Programs (AAHRPP).

It will not be easy. All stakeholders will have to come together. They will have to ignore their silos and work hand in hand to change the negative perception and ensure greater discipline and self regulation. The threats will come from within the ranks.

Inspiration should be taken from a group in Mumbai called ‘Responsible road users club’. Members of this group brave all the taunts and honks from outside and within to steadfastly follow road safety rules, even when their own friends and family push them to break red lights.

Such single minded doggedness will be required by each member and stakeholder of the clinical research fraternity if the industry is to recover from the black hole it finds itself hurtling towards.

Note: The views expressed represent the personal opinion of the author.