Cushioning the fall

Cushioning the fall

Clinical trial insurance can help cushion the risk associated with drug trials. But is there adequate awareness of these products? Usha Sharma reviews the situation

India is emerging as a final destination for global clinical trials (CTs), due to availability of vast pool of patients and also well trained medical professionals and good infrastructure. Most US and European nations are outsourcing CTs activities to India. The companies like sanofi-aventis, Glenmark, GlaxoSmithKline (GSK), Roche, Dr Reddy’s Laboratories, Ranbaxy, Pfizer, Bristol-Myers and Merck are the leading players conducting CTs in India.

According to the Associated Chambers of Commerce and Industry, CT business is likely to grow to $1 billion by 2010. Global consultancy McKinsey & Co estimates that by 2010, global pharmaceutical majors would spend around $1-1.5 billion for trials in India. Industry experts estimate that by 2012 nearly five percent of global trials will be done in India.

As the number of trials and the complexity has grown dramatically, there is an increasing demand for appropriate risk management measures like Clinical Trial Liability Insurance. Regulatory authorities are also tightening controls on ethical standards adopted and CTs processes. Inspite of recent high profile tragedies, there is inadequate awareness coverage in terms of most companies purchasing low limits of liability and inadequate data to process claims. “(Human) Clinical Trial Insurance (HCTI) process helps pharma companies as a tool to manage their clinical trial /bioequivalence (CT/BE) related risk, which is required for regulatory/ ethics committee compliance purposes. In fact it is compulsory in many countries,” says Alok Agarwal, Director, ICICI Lombard General Insurance Company.

Most of the time, these policies are written for a period of one year and incase of spill-over there is a provision for retroactive coverage during renewal. Giving more details, Alok Agarwal says, “There could be coverage for multiple trials under a single policy. The policy is usually written on ‘named trial’ basis, ie. the insured has to declare information related to the trial before inception. The pricing depends upon various parameters like the nature of the molecule, phase of study/trial, number of patients/subject, limit of indemnity, loss record etc”.

Why HCTI?

“At present very few insurance companies write such policies as it is a highly specialised product, which demands sound product knowledge and intricate underwriting”

– Alok Agarwal Director

ICICI Lombard General Insurance Company

“Most ECs insist on the presence of an insurance certificate. The problem is that many members do
not understand the fine print of the HCTI and hence accept the certificate at face value”

– Dr Renuka Kulkarni-Munshi Associate Professor and In-charge Department of Clinical Pharmacology TN Medical College and BYL Nair Ch Hospital

Mumbai Central

HCTI basically works as a shield for any organisation against any claims which can arise during a particular test or protocol. It also indemnifies the insured against all claims. HCTI can be purchased by the organisation that is responsible for compensating or indemnifying the volunteer, which in the majority of cases is the sponsor pharma company or the Clinical Research Organisation (CRO) for conducting the trial. Apart from the sponsor and CRO, HCTI policy protects the interests of the medical investigator and ethics committee (EC). Most policies are taken by sponsors or pharma companies but recently, industry observers note that CROs in India have started showing an interest in buying such policies. The therapeutic areas that have attracted major claims are Central Nervous System (CNS) and cardiovascular system.

Dr Renuka Kulkarni-Munshi, Associate Professor and In-charge, Department of Clinical Pharmacology, TN Medical College and BYL Nair Ch Hospital, Mumbai, highlights the HCTI needs for HCTI in India saying, “HCTI gives an assurance that the volunteer/patient will be taken care off, in case something goes wrong in a CT. It ensures that the sponsor has taken the responsibility of taking care of the trial subject for any trial related injury, legal costs and expenses incurred by the insured in connection with the defence or settlement arising out of the claim and or agreed compensation paid by the insured to the research subject on death, disability etc. All corporate sponsors including those marketing allopathic drugs, herbal drugs and vaccines, government agencies and investigators who conduct academic studies should apply for HCTI.”

HCTI players

Insurance players in the Indian market offering HCTI products falle into two categories: private companies and Public Sector Units (PSUs). Private insurers include ICICI Lombard, HDFC Ergo, Bajaj Allianz, Cholamandalam, Reliance and Future Generali Among PSUs Oriental Insurance, United India Insurance, New India Assurance and National Insurance Company service this segment. Global players include the Australian QBE Insurance Group, Ace Group, Canadian insurance provider Chubb Insurance. Munich Re Group, Allianz Insurance, HDI-Gerling Life Insurance Group, Zurich Financial Services and British insurance provider company Lloyd’s of London. Internationally the insurers who can act globally are HDI/Gerling, Allianz, ACE, QBE, Chubb, Zurich and Lloyds. All the issued policies by the private insurers are usually re-insured by The General Insurance Council (GIC). There are a number of other insurers who also have a capability are mainly Navigators Group, CNA Insurance, Newline Insurance Company (Lloyds) but these do not profess to have a network which will cover 156 countries.

Country Global status of laws on HCTI
US It is not mandatory by law for sponsors and institutions to provide either free medical care or compensation for research related injuries to trial participants, apart from general tort law principles that apply to everyone.
Europe Many European countries mandate the provision of clinical trials insurance, through which subjects are often covered regardless of fault. Countries such as France, Germany and Spain, have compulsory insurance laws with variations in the specifics and minimum coverage required.
UK The Association of the British Pharmaceutical Industry guidelines on compensation for trial related injuries also recommend that subjects suffering from research related injuries be compensated on a ‘no fault’.
South Africa, Australia and New Zealand The Uk guidelines have been also adopted by South Africa, Australia and New Zealand. Unfortunately, these guidelines clearly state that there is ‘no legal commitment’ to pay compensation for research related injuries thus not adequately protecting research participants.

Legal framework

As per the Indian Council of Medical Research (ICMR) Ethical Guidelines / Good Clinical Practice (GCP) framework, it is obligatory for the pharma company, sponsor or the institution conducting trials to compensate research subjects for serious adverse reactions, disability or death. India has not seen many claims under HCTI even in the high risk segments, like cardiovascular, medical devices, neuro molecules etc. But claims in this segment are highly unpredictable. Kulkarni-Munshi, highlights the situation, says “The issue to be addressed today is awareness among sponsors and investigators about the need for insuring trial subjects.”

“At present very few insurance companies write such policies as it is a highly specialised product, which demands sound product knowledge and intricate underwriting. We receive proposals from both domestic and global players. In fact, these days there is a surge in queries from global players who conduct trials in India,” Alok Agarwal reveals.

Way to work

“The EC needs to satisfy themselves that the trial is well
organised, safe and also appropriates the measures which are in place to compensate anyone who suffers bodily harm whilst participating in the trial. In the majority of cases insurance is used to satisfy that compliance”

– Mohit Agarwal Senior Vice President FINPRO

Marsh India Insurance Brokers

“The role of EC depends on the role assigned to the EC by local statutes”

– Dr S M Sapatnekar

Director and Dean

Clinical Research Education and Management Academy

“The limit of CTI liability depends on many parameters
such as disease under studies are ongoing, phase of the CTs; turnover of the company, local and international presence, types of clients, number of test and protocols”

– Binoy Gardi
Co-Group Managing Director and Co-Founder Veeda

Mohit Agarwal, Senior Vice President, FINPRO, Marsh India Insurance Brokers explains the process of HCTI application. “The applicant needs to send a proposal form covering some related queries related to the regulatory approvals, limits etc, trial protocol and patient consent form (unsigned). Based on this information, brokers prepare a market submission and send it across to the insurers. The insurers then send across their premium quote based on how they perceive the risk, “ he says. “The broker then prepares the quote comparisons highlighting the premium and other terms offered by other insurers. The applicant can decide with which insurer to bind the policy and the policy gets bound on payment of premium.”

Due to the complexity of the product to be insured the parameters are very specific. Expanding on these parameters, Binoy Gardi, Co-Group Managing Director and Co-Founder Veeda Clinical Research says, “The limit of HCTI liability depends on many parameters such as disease under study, phase of the clinical trial; turnover of the company, local and international presence, type of client, number of tests and protocols. It also depends on the number of participants in the trial, in the duration, risk associated factors and study medication details such as anti-cancer drugs, which have a higher risk.”

EC as a watchdog

The role of ECs is pivotal to the HCTI procedure as EC members have to approve the trial protocol and have to be satisfied that the sponsor is complying with legislation or regulations so permitting the trial to commence. The consent letter or form does specify all the risks involved because as per international norms of HCTI as well as regulatory compliance required in various geographies, it is compulsory to insure volunteers on CTs against all physical, mental and internal occurrences from the trial. The consent form mainly informs the participating research subject of the possible adverse reaction that have been reported so far. It also states that the adverse reactions of the particular subject may be more severe or may not even have been reported before and thus he or she has full right to receive the medical expenses incurred due to physical injury, temporary or permanent impairment or compensation for disability and death.

ICMR has been active in CT domain and ICMR guidelines of 2006 inter alia states that: ‘Each research (study) should include an in-built mechanism for compensation for the human participants either through insurance cover or any other appropriate means to cover all foreseeable and unforeseeable risks by providing for remedial action and comprehensive aftercare, including treatment during and after the research or experiment. With respect to any effect that the conduct of research or experimentation may have on the human participant and to ensure that immediate recompense and rehabilitative measures are taken in respect of all affected, if and when necessary.’

Dr S M Sapatnekar, Director and Dean, Clinical Research Education and Management Academy says that, “The role of EC depends on the role assigned to the EC by local statutes. Recently, Indian Society of Clinical Research (ISCR) an independent scientific organisation has offered detailed recommendations to ICMR with regards to insurance of subjects.”

Mohit Agarwal emphasises the EC’s core responsibilities, “The EC needs to satisfy themselves that the trial is well organised, safe and also appropriates the measures which are in place to compensate anyone who suffers bodily harm whilst participating in the trial. In the majority of cases insurance is used to satisfy that compliance.”

Alok Agarwal explains that, “Because there’s surge in CRO business as its growing exponentially and it set to become a billion dollar sector within next few years, during recent times the awareness among pharma industry players has amplified. In developed markets like US and EU the policy is compulsory for sponsors or CROs. Most ECs have made it mandatory for sponsors or CROs to produce proof of insurance covers before granting their approval.”

Mohit Agarwal further explains that, “The insurance provider company’s collective footprints get stretched by the fact that in most of the world you need to issue local documentation in local language which is a challenge. Currently, we (operate in) 156 countries and these insurers would need to work with partners in many of the emerging locations. Also in Europe the insurers like to issue Freedom of Services policies as permitted by EU insurance and competition law. However, this approach would require acceptance by local EC which can be negotiable and open to interpretation and acceptance.”

Kulkarni-Munshi, points out that, “Most ECs now-a-days insist on the presence of an insurance certificate. The problem is that many members do not understand the fine print of the HCTI and hence accept the certificate at face value. So ECs should be trained to be familiar with and understand the necessary details such as whether the insurance coverage is commensurate with the risk involved in the study that need to be looked at in a HCTI prior to giving approval to a trial.”

HCTI coverage and claims depends on which stage of the trial is to be insured. Alok Agarwal states that, “Phase I has highest severity but low frequency whereas phase III may be low in severity but high frequency since at this stage a drug is administered to about 100 subjects. As of now around 60 percent of total Indian trials are at phase III. The claims management process involves a medico-legal person (from insurer side) who recommends compensation and then accordingly an offer is made to the plaintiff.”

No of (%) Stakeholders with positive replies

Question

Investigator
(30/140)

EC member
(23/96)

Sponsor/CRO
(27/37)

General awareness of the requirements as per Indian laws and guidelines regarding provision of clinical-trials insurance and/or compensation for injuries during clinical trial 16 (53) 17 (74) 24 (89)
Whether the institution/organisation has a policy for managing compensation issues 12 (40) 7 (30) 27 (100)
Whether the institution/organisation has mechanisms for grievance redressal of a research subject? 11 (37) 14 (61) 14 (52)
Number of instances where compensation been provided? 1 (3) 2 (9) 4 (15)
Do you agree that the subject should be compensated for the loss of time/wages due to injury? 6 (20) 4 (17) 13 (48)
Does your institution make provisions in the trial budget for research related injury claim 6 (20) 20 (74)
Does your ethics committee expect a deposit in advance from the sponsor to manage research related injuries prior to granting permission for a clinical trial? 4 (13) 4 (17) 2 (8)
Does the sponsor have to bear the entire financial responsibility of the compensation claim? 30 (100) 3 (13) 27 (100)
Does your organisation enter into a contract with an insurance agency regarding the finances for research related injury claims? 5 (17) 4 (17) 20 (74)
Is it required for the subject to pay first and then be compensated after providing proof of such a payment? 20 (67) 11 (48) 11 (41)
Is legal advice sought prior to accepting compensation claims? 11 (37) 6 (26) 25 (93)
Source: Review of policies for injuries to research participants in India U M Thatte, R Kulkarni-Munshi and S A KalekarJ. Med. Ethics 2009;35;133-139

doi:10.1136/jme.2008.025155

Indian Scenario

Unfortunately, a recent study conducted to assess policies available in case of research related injuries, showed that India has a long way to go before participants on drug trials can rest assured that they will be taken care of should they be the encounter adverse effects. The study was done by Dr UM Thatte Associate Professor, Department of Clinical Pharmacology, TNMC & BYL Nair Hospital, Renuka Kulkarni-Munshi and Samidha A Kalekar, Senior Research Fellow. Results of the study, are summarised in Table 2. According to the study report, in India, there are no uniform policies and investigators are largely unaware of their responsibilities. Therefore, there is an urgent need to draft national guidelines regarding compensation for research injuries of research participants and highlight the responsibilities of each stakeholder. The potential research injuries should be categorised based on risk assessment, severity and seriousness of the injury. Further, it would be necessary to have arbitration committees to determine the extent of compensation.

Presently, most big pharma companies provide insurance coverage for CTs and there are cases where when the EC insists, smaller players also do. “The main issues that need to be addressed are trials that are done mainly by small pharma companies and CROs, herbal pharma industry and government agencies that do not provide for insurance coverage. The reasons vary from lack of awareness to cost cutting measures,” Kulkarni-Munshi stresses.

However, Mohit Agarwal avers, “In my opinion one of the major challenges facing insurance is a need to consider cover for completed trials. CTs policies are written on a ‘claims made’ wording certainly in the majority of the world as far and once the trial is completed there is a requirement for ‘run-off’ cover. I think the understanding of this exposure is not often understood by those who purchase insurance.”

HCTI policies may also soon become controversial as the scale of insurance coverage varies across countries. Commenting on this, Kulkarni-Munshi says, “Other issues that we have noted in the study are the fact that insurance coverage provided to Indian participants is lesser than that provided to trials conducted in the USA or other European countries. Also, the insurance document per is so complex and in technical legal language that it is difficult to make ‘head or tail’ of it so most investigators don’t even bother to read the document. Only if ECs and investigators insist will sponsors ensure that HCTI is provided for all types of studies. Training should also be offered to understand the nuances of how the coverage is determined so that each player (EC, investigator and sponsor) can confirm that adequate provisions are being made.

On the HCTI front, Kulkarni-Munshi urges that HCTI providers need to make the process of calculating and obtaining insurance more open, easy to understand, how risk is calculated per occurrence etc and accessible. Also presently, most of the underwriting for the HCTI is done abroad and then changes are made for the Indian situation. She opines that HCTI providers therefore need to be trained so that they can work independently and answer queries confidently.”

So while the HCTI market potential is huge, it is currently constrained by low awareness levels. To unlock this potential, as well as protect corporate stakeholders and most importantly the trial participants, there is an urgent need for training and awareness workshops for all those involved in clinical research, including research participants. Insurance companies too need to be aware of issues from a patient’s perspective.

u.sharma@expressindia.com