Insurance best practices for human clinical trials

February 05, 2018

Clinical Trials are Everything But Riskless!

On January 15th, 2016, we learnt that a dramatic event had just occurred involving a Phase I clinical trial in France: the death of a participant. This trial was involving a stage of first administration to humans of the Bial medicinal product "BIA 10-2474". It was conducted only in France (at the Biotrial research site in Rennes) and involved healthy volunteers, men and women aged between 18 and 55 years.

The protocol was split into three parts :

• 1st part: administration of single ascending doses (SAD). No serious adverse event was brought to the knowledge of French health authorities during this first part of the trial.
• 2nd part: interaction with food.
• 3rd part: administration of multiple ascending doses (MAD). No serious adverse events were brought to the knowledge of ANSM from cohort 1 up to the end of cohort 4. Serious adverse events occurred after the 5th (and last) cohort was given the tested drug.

Less than ten days after the start of treatment of the fifth cohort, the trial was suspended as six healthy volunteers were hospitalised out of the eight volunteers’ cohort (out of which two received a placebo). One of them went into a coma and died a few days later; four others suffered serious neurologic troubles.

When writing this article (December, 2017), the liability of all parties involved is still undetermined and investigations are ongoing.

In 2006, the TeGenero clinical trial in London also made a lot of noise in the life sciences industry when six healthy volunteers suffered serious reactions within minutes of dosing, leaving them in intensive care with multiple organ failures (an incident described by some as the biggest setback for medical testing since thalidomide).

In the case of TeGenero, the situation ended in bankruptcy; their insurance coverage of two million English pounds was insufficient to meet the required amount for compensation of the victims. But the consequences can also go beyond insolvency and the relinquishment of the clinical trials: it can result in irreparable damage to the reputation of the organisation and the entire industry, which is already facing challenges to attract more participants to clinical trials.

Even if human clinical trial accidents rarely happen, they can engender serious bodily injuries that could lead to death. This is why most of the countries have enforced requirements (following Good Clinical Practices – ICH-E6) to protect volunteers participating in clinical trials. One of the recurrent requirements is that the sponsor shall buy an appropriate insurance policy in case volunteers – suffer bodily injuries during the trial; "clinical trial insurance".

To Be Well Insured or Not To Be!

Some readers could think that once you have said that insurance is a requirement for running human clinical trials in most of the countries, you have closed the discussion. Actually not! as being insured means everything and nothing!

Local requirements are very different depending on the country where the sponsor runs a clinical trial. A single policy being unable to meet the requirement of a multi-country trial, each country involved in a trial has to be covered with a specific insurance. That is why finding the appropriate insurance is a nightmare for most of the sponsors. Let us show you how insurance requirements can be different from one country to another.

> Mandatory vs Optional Insurance
First of all, clinical trial insurance is not mandatory in all countries (even if highly recommended). In Belgium, for example, it is mandatory to contract clinical trial insurance. The insurance certificate is requested prior to submitting protocol to ethics committee. Whereas in the USA, the insurance is not a pre-requirement and therefore no authorities will ask you to prove that the sponsor is covered for the clinical trial.

> Local vs Foreign Insurance
Imagine you are a Californian sponsor ready to launch a Phase II trial in the US, Singapore, Germany and Brazil. You may think that the US insurance policy you are about to buy will also protect you against claims arising out of patients’ enrolment in the three other countries… But that is not the case!

Your US insurance policy, if correctly designed, can protect you for the Singapore part of the trial as the Republic of Singapore allows insurance of Singaporean risks from a foreign country. In our insurance jargon, we used to say that non-admitted insurance is allowed for clinical trials in Singapore. This means that an insurance company which is not registered in the country is allowed to provide insurance solutions.

Brazil is the opposite, as non-admitted insurance is strictly prohibited so the Californian sponsor shall find a local insurance solution to protect its liability.

The last example is Germany. In this European country (as in most European countries), non-admitted insurance is also prohibited but a solution coming from a country which is part of the European Economic Area (EEA) is allowed thanks to the “European Freedom of Services” rules.

> Liability vs Accident Insurance
Keep focusing on Germany. In this country, human clinical trials’ insurance solutions shall be accident insurances. This is a kind of insurance which directly protects the volunteers without any consideration of which party (sponsor, investigator, CRO) could be liable.
In some other countries, even in the European Union, required insurance is a liability insurance with insurance policy wordings and rules that are completely different from those applying to accident insurance.

> Insurance Limits
This is another topic which cultivates differences between local requirements. Some countries only require the sponsor to purchase ‘an insurance’, while others also require minimum coverages.

In the UK, for example, a five million GBP limit (per protocol) will be necessary for sponsors running a “first in man” drug trial. Now going to Australia, in the State of New South Wales, the liability insurance policy shall have a limit that cannot be lower than twenty million AUD!

> Extending Reporting Period
This is one of the liability insurance characteristics which is the least known, although it is one of the most interesting.

The Extending Reporting Period (ERP) definition is “a designated time period after a policy has expired during which a claim may be made and coverage triggered as if the claim had been made during the policy period”. And why could this characteristic be so interesting? Let us explain it using the following example:

In Italy, and depending on the tested product, the ERP shall not be less than three years, and even more if a drug is tested on children; the ERP will go on till 10 years after the child’s majority. This means that the insurance policy purchased by a sponsor for a trial including children who are five years old will have to cover claims for bodily injuries that could occur till children are 28 years old… that is to say, 23 years after children have been included in the trial.

Let us look at the same protocol (with children) in the US: there is no requirement for ERP in clinical trials insurance policies. So if a child suffers from bodily injuries a few months after the end of the policy, there will be no more insurance cover to protect the sponsor against claims.
Therefore, the ERP is very protective for both patients and sponsors, and we can only recommend making sure that the insurance cover you get includes at least one or two years’ ERP.

There are lot of other insurance differences hidden in country requirements! That is why it is so important for sponsors to use both skilled insurance brokers and reliable insurance companies.

Insurance Company and/or Insurance Broker?

When launching a human clinical trial, the choice of the insurance companies that will be used is very important, because in case of serious adverse events during or after the trial, they must be a partner that will assist you and indemnify properly.
We used to say that an insurance company is reliable for at least four reasons :

• first, it has skilled underwriters who understand the protocol and associated risks,
• then, it issues policy wording which complies with countries’ local requirements,
• it has efficient and skilled claims resources,
• and last, but not least, it is strong enough (from a financial point of view) to pay claims.

Why should you use a skilled insurance broker if you have already identified reliable insurance companies?

Let’s summarise what we call a skilled insurance broker :

• It has experience in both insurance and life sciences risk management. Do not think that a former PhD who decided to sell insurance policies will automatically be a skilled broker. He might be able to speak about recombinant proteins for hours but not able to manage ERP issues!
• It has a large clinical trials portfolio, not only in its own country but on the five continents.
• It has already experienced claims management in the field of clinical trials insurance.
• It has people who understand/speak a minimum of English as most of the documents/meetings in the fields of clinical trials are in English.
• It has reliable and available process as clinical trials insurance requires changes, sometimes a few hours before an ethics committee submission.

Back to our question: ‘why use a skilled insurance broker?’

We would start with the easiest part of the answer: because only skilled insurance brokers are able to identify the reliable insurance companies which will cover your clinical trials. And that is not a joke! We know best-in-class insurance companies which still issue non-admitted insurance policies in countries where it is strictly forbidden.

As the economic goal of insurance companies is to sell insurance premiums without paying too many claims, they may sometimes forget to suggest good solutions, such as a proper ERP, for example. The skilled broker will automatically request this “post-trial” cover. It is a real insurance advisor for sponsors.

Also, in order to get competitive insurance premiums, it is better to negotiate with several insurance companies because company A could be competitive for a trial in South Africa and very expensive for the same trial in Argentina. So, for each country (but for countries where there is no choice), it is necessary to request quotes from different insurance companies. And what about our skilled insurance broker? He/she will be able to negotiate with several insurance companies and to really compare quotes so the sponsor will be sure to make the best choice.

Before and during the trial, the skilled insurance broker is also able to assist sponsors in their discussion with CROs or investigation sites as in contracts between these entities there is always a chapter on indemnification and/or liabilities and/or insurances.

The last part of our answer concerns claims management. Serious adverse events (SAEs), such as those which happened during the TeGenero (2006) or the Bial (2016) trials, are very uncommon. But there are also each year some SAEs, less serious and/or less highlighted by the media, which need to be accurately managed. For this, your skilled insurance broker will be the “orchestrator” and the permanent link between the sponsor and insurance companies.

Other Items Sponsors Should Check

• The sponsor shall be named on insurance documents (certificate and policy).
• Check your insurance limits and ERP are in accordance with the CRO/sites agreements. Also, be sure liabilities are clearly described in these agreements.
• The patient information sheet (PIS) is a key document in case a claim is made by a participant! Make sure that it is written in a comprehensive language (for a non-scientist) and that it describes properly the procedures and the risks incurred (adverse effects).

The choice of clinical study insurance is not trivial, and an error could lead to serious consequences for the sponsor. Regardless of the responsible party, as long as insurance is properly in place, the insurance process can be triggered to defend the insured parties involved, even sometimes before liability is established. The best practice is certainly to get help from professionals to better negotiate covers and premiums. There are a few insurance brokers which specialise in clinical studies. Due to their knowledge of the local requirements as well as the insurance market, they are the ideal partners for any sponsor concerned with risk management issues!

Sandrine Bresard
Co-founder and CEO of i4CT – Insurance for Clinical Trials – a French insurance broker providing worldwide solutions for human clinical trials insurance. After being involved on various international projects, she now makes sure i4CT benefits from the highest level of service and technology with its unique online clinical trial insurance solution: www.i4CT.com

Frédéric Nouaille
Co-founder and Chairman of i4CT. He held several positions before, including complex risks and liability underwriter. Frédéric is also currently CEO of Audit&RiskSolutions and is regularly invited to speak during international meetings concerning life sciences insurance issues.

Published on February 5th, 2018 in the Journal for Clinical Studies - Volume 10 Issue 1:
https://issuu.com/mark123/docs/jcs-jan18-web/26/

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