Clinical Trial Data Transfer In The Aftermath Of No Deal Brexit

Quick Refresher: As established by the EU GDPR when it first took effect in May 2018, any company that handles the data of any EU citizens – whether or not that company is based in the EU – must adhere to stringent GDPR regulations regarding data privacy and protection.  Data can include anything from name, email address, medical information or biospecimens. But now that the UK is withdrawing from the EU and no longer covered by the GDPR as an EU Member State, what does that mean for data privacy and the flow of clinical study data, such as adverse events reports, samples and central lab data?

What Happens to Data Protection Services and Appointment of UK Entities as Sponsor Representatives under GDPR?

Amidst the many uncertainties raised by a hard Brexit, questions exist as to what steps US sponsors should take to ensure their study data continues to move across borders without interruption – in particular, whether the current data representative services agreements with their CROs will be, well, moot or functional after Brexit. We at CA have noticed that many of the CROs party to our client’s data representative services agreements (agreements by which one engages a CRO to perform a sponsor’s EU data controller obligations and appoints the CRO to be its EU DPR under the GDPR) enter into them using their UK entities. Questions about the validity of these agreements will not be definitively answered until after the UK strikes a deal with the EU, or, alternatively, the UK crashes out of the EU with no deal. For now, the sponsor can only attempt to prepare and plan for any possible Brexit outcome as the future is unknown.  It is clear that no US sponsor study data can be processed in the EU without a validly appointed data protection representative (again, this appointment is a longstanding EU and now a GDPR requirement for US sponsors with no EU presence), but it is not clear whether or not the remaining EU member states will accept or recognize the appointment of a UK CRO.

Remember, the UK will still need to comply with GDPR, even though it’s no longer a member state of the EU due to GDPR’s extraterritorial reach. However, in the absence of a Brexit deal, the UK will become a “third country” and will be tasked with proving to the EU that its data protection laws (the UK Data Protection Act, more below) are “adequate”, or compliant with GDPR standards to allow for seamless data transfers to the UK from the EU.

A best practice for companies would be to carefully track the impact of Brexit on processing data of EU citizens in the next 50 or so days. The UK Information Commissioner’s office has published some helpful information. If it seems like the company’s data flows might be negatively impacted by a no-deal Brexit or the UK’s status as a third country with no adequacy rating, then the company should consider implementing contract-based mechanisms that would help mitigate any interruptions in data sharing. In some instances – but not all – certain contractual clauses could be drafted to allow data transfers from the EU to the UK. The EU model contact clauses, which can be used to amend existing agreements to ensure adequate, can be found on the European Commission website.

How does the UK Data Protection Act Differ from the EU GDPR?

The EU GDPR expressly allowed/encouraged the member states to pass local data protection legislation that augmented and worked in tandem with GDPR standards. Germany and the UK were two of the member states that had their local legislation at the ready and right away, the UK Data Protection Act of 2018 was passed. The UK DPA of 2018 Chapter 2 expressly adopts all GDPR definitions and supplements it, and Chapter 3 applies to certain types of “…personal data to which the GDPR does not apply (see Section 21), and makes provision for a regime broadly equivalent to the GDPR for such processing.”

Is the UK ready to amend its legislation to allow uninterrupted transfer of personal data after March 29, 2019?

Yes. The UK government has an existing Department for Digital, Culture, Media and Sport (we have nothing like this in the US, but we should!) and they have a legislative amendment ready to go. It seems as if the UK domestic law will preserve GDPR standards, by amending the UK DPA of 2018 so that “obligations and rights that organisations and data subjects have become familiar with will stay the same”.  It also appears likely that the UK will deem all EU Member States and EEA countries as “adequate” – a rating meaning that the territory employs an appropriate or “adequate” level of data protection safeguards – with the hope that the data flows between the UK and the EU and EEA countries will continue with minimal disruption.

The new legislation is called the “EU (Withdrawal) Act of 2018 (EUWA) and it will retain the GDPR in UK law and make changes necessary to ensure that the UK obtains the “adequacy decisions” its businesses and its government (law enforcement and security agencies need to transfer data too) will need to continue to function after March 29, 2018. EUWA is not final but the technical notice it filed in September 2018 was encouraging in that it anticipates “no deal” and therefore could actually be functioning on Day 1. See, “Data Protection if there’s no Brexit deal”.

Contracts Associates is prepared to help your company successfully navigate the possibility of a no deal Brexit. Our team of attorneys will work to help your company uphold its legal duties and obligations to EU sites and vendors by drafting new contract template terms as needed. We encourage you to contact our office with any questions at 781-598-8000 or by emailing our CEO, Colleen Sproul, at cms@contractsassociates.com

 

No Successor Yet Named For Head of UK Medicines Agency

As the deadline date for the UK withdrawal from the EU rapidly approaches, no successor has yet been named to take the place of the head of the UK Medicines and Healthcare Regulatory Agency (MHRA).

Late last fall, Dr. Ian Hudson announced that he will resign his position as CEO of the MHRA. Dr. Hudson has served as CEO of the watchdog agency since 2013 with much of his current role including serving as the UK delegate to the Committee on Human Medicinal Products (CHMP) at the European Medicines Agency (EMA). Indeed, Dr. Hudson has been the Vice-Chairman of CHMP since October 2012.

Dr. Hudson does not appear to be leaving for a particular employment alternative, rather, he stated, “I feel the time is right for a new person to guide the agency and our work through its next phase, following the UK’s departure from the European Union next year.” The resignation will take effect in September 2019, about six months after the UK leaves the EU.

With only two months to go before the March 29, 2019 Brexit date, there remains no deal in sight. According to its long-term Brexit plan, MHRA is moving forward with preparing for the possibility of a hard Brexit.

MHRA Post-Brexit

If the UK exits the EU without a deal which includes provisions for a relationship with the European Medicines Agency, the MHRA will lose access to all EU regulatory networks and will serve as a standalone drug regulator – handling all responsibilities that are currently overseen by the EMA, such as drug approvals, general oversight of medicines, and clinical trials. The MHRA has released some proposed arrangements for regulation in the case of a no-deal scenario.

The resignation of Dr. Hudson and the search for a successor to guide the agency adds a yet another layer of uncertainty as to the future of the MHRA in the aftermath of Brexit.

As the March 2019 UK withdrawal date approaches, we at Contracts Associates will continue to provide updates on our blog in relation to the impact of Brexit on existing appointments of UK entities as EU legal representatives as well as recommended revisions to UK informed consents, once the UK is no longer subject to the EU GDPR.

When Sponsors Need a Lifeline, Rescue Contract Reviews Can Get a Clinical Trial Back on Track

Delays can be the death of a clinical trial. Late starts and missed milestones can deteriorate sponsor-site relations and waste both parties’ time, resources, and patience. And when studies get off to a shaky start, it’s all too easy to rush other obligations in a desperate bid to make up time—jeopardizing the study’s success.

Due to a lack of in-house resources or legal expertise, many sponsors find themselves unprepared to strategically negotiate these agreements within the available time frame before a trial’s projected start date. This makes it even more difficult to secure mutually beneficial terms and maintain a positive working relationship with the site.

When it looks like a study is hitting a standstill, agile legal vendors like Contracts Associates can swoop in to save the day. “Sometimes after entering into an agreement with a CRO, a sponsor finds that they’ve under-resourced. They don’t have the legal support they need. That’s where we step in,” says Contracts Associates President and Founder, Colleen Sproul. “We’ve performed fast and reliable “rescue contracts reviews” for countless sponsors over the years, helping to support our clients in meeting their milestones.”

Here are some areas where sponsors commonly run into trouble, and where a rescue reviewer can help get you out of the weeds and on track to meet your milestones.

Approaching contract reviews without experienced negotiators on your team

Negotiating contract terms is always a balancing act. You have a budget and timelines to consider, and intellectual property and a reputation to protect. And if your site is a major research institution, it’s more than likely that their vast and experienced legal team is combing over every clause with an eagle eye.

Unfortunately, some sponsors lack the in-house legal knowledge to negotiate equitable contract terms and handle reviews with the necessary efficiency. And without a thorough and strategic approach to contract reviews, all manner of unfavorable terms can slip through the cracks. You may find yourself taking on unnecessary responsibilities and shouldering a troubling level of risk. And if you don’t pay close attention to the agreement, the investigator may be entitled to publish data long before you’re ready to see it go public.

The idea that any agreement is better than no agreement is a damaging one. If you find your company struggling to finalize a favorable clinical trial agreement with target deadlines looming, take a step back before signing and harness experienced outside help.

An outsourced legal vendor with experience in rescuing contract reviews can enter the review process to expedite negotiations, smooth out seemingly inflexible terms, and help find a mutually-beneficial middle ground—so you don’t have to settle for the simplest compromise.

Rushing into an agreement because the in-house legal team is overwhelmed

Even sponsors with in-house legal teams can run into these delays. In the buildup to a clinical trial, the rush to meet milestones can quickly cause in-house counsel to get stretched too thin—leading to a backlog of contracts waiting for review. This opens the door to mistakes and missed opportunities, slowing the process down significantly.

The time and expense it takes to hire and onboard another full-time attorney would only exacerbate the delay. This can leave sponsors stuck between a rock and a hard place, unable to expand their team but incapable of meeting their milestones with the resources they have.

Outsourced legal solutions can solve this problem, offering rescue contract reviews on an as-needed basis. Your in-house counsel is supported by an entire team of lawyers who share their industry knowledge and don’t require explanations before getting to work. This allows you to ensure that every term is meticulously crafted and any loopholes effectively tied up—before you make them legally binding.

Rescuing contract reviews, supporting sponsors at every step

At Contracts Associates, our firm was founded to steer sponsors toward success—and our rescue contract review services have helped many of our clients get there against the odds.

All our lawyers match deep contract review knowledge with extensive in-house experience and established relationships with prominent research institutions. This allows us to enter the contract review process at any stage without wasting time getting up to speed or aggravating strained relationships between sponsors and sites.

And since our attorneys work remotely, we’re able to work flexibly and work fast—so you can meet your milestones and avoid endless (and costly) delays.

Of course, no sponsor sets out thinking they’ll need rescue services. Prepare for any eventuality and ensure your success by having a solid contract review plan in place from the very beginning. We can help. From crafting meticulous contracts to creating a customized library of agreements for your company, we can support you from the outset—so you can enter the clinical trial phase with confidence.

Ready to expedite your contract review process? Contact us today.

How EU GDPR Affects Collection of Biometric and Genetic Data

As we look toward the new European Union General Data Protection Regulation (GDPR) which takes effect this week, we expect some of its provisions to affect U.S-based life sciences companies conducting clinical trials at EU sites, particularly related to the collection of genetic and biometric data.

GDPR governs how data controllers and processors are permitted to engage with the personal data of EU citizens.  The new legislation differs from the former controlling legislation, the Data Protection Act, in some key ways. GDPR is broader in scope than the previous directive meaning that, as of May 25, 2018, even non-EU based companies will be subject to more extensive regulation.

GDPR implements a new extra-territorial rule, so that no matter if a company is based in the EU or not, it is still bound by GDPR if certain criteria are met. For example, even if a data controller (i.e., a sponsor) or processor is not established in EU, they will be bound by GDPR if they’re processing the data of individuals within the EU. Sponsors in the U.S. may now find themselves obligated by the GDPR privacy protections where they were not bound before. Member States are also free to impose further restrictions on the processing of health-related data.

The life sciences industry and clinical studies are clearly reliant upon the data that are collected from participants within clinical trials. GDPR introduces new, explicit privacy protections for such health-related data.

GDPR specifically categorizes genetic and biometric data—which is the type of health data upon which clinical trials largely rely—as “sensitive personal data”. Under GDPR, the processing of genetic or biometric data is prohibited unless an exception applies. In the clinical trials context, an exception that might commonly apply is gaining the consent of the data subject.

In an effort to protect the interests of individuals where an imbalance of power could occur or the possibility of serious data protection risks exist, GDPR has heightened the standard of consent to mean “any freely given, specific, informed and unambiguous indication of the data subject’s wishes by which he or she, by a statement or clear affirmative action, signifies agreement to the processing of personal data related to him or her.”

This definition will provide the framework for sponsors gaining the necessary explicit consent from individuals who are considering joining a clinical study, such as via a written statement or informed consent contract.

As we approach May 25, 2018, sponsors must ensure that all informed consent contracts are compliant with GDPR and meet explicit consent standards as well as all other contractual obligations so that all prospective participants are protected and the sponsor is in compliance.

Contracts Associates has been working to help our clients navigate this new regulatory framework. Our team of attorneys has the deep experience and expertise necessary ensure that all of your informed consent agreements meet the higher bar that GDPR has introduced. We help our clients minimize the risk of penalties by updating contracts and providing reviews to ensure that all informed consent language is GDPR-compliant. If you haven’t yet contemplated how GDPR might change affect your study, please contact our CEO, Colleen Sproul, at cms@contractsassociates.com or call 781-598-8000 so that we can help guide you.

UPDATED MAY 31, 2018: House Passes “Right to Try” bill – Compromising Public Health and Drug Development

UPDATED MAY 31, 2018

On May 30, President Trump has signed the “Right to Try” bill into law which allows terminally ill patients to bypass the FDA when attempting to gain access to experimental therapies. Patients have already been able to apply for investigational drugs outside of clinical trials via the federal “Expanded Access” law.

The Right to Try legislation does not guarantee that manufacturers will provide the drugs nor that insurance companies will cover the costs. The law was backed by libertarian think tank the Goldwater Institute.

Originally published on April 18: On March 21, only one week after an initial defeat in the U.S. House, the controversial “Right to Try” bill was passed by a vote of 267-149. The legislation is now on its way to the U.S. Senate.

“Right to Try” would provide access to experimental therapies to patients with life-threatening illnesses while weakening FDA oversight and compromising public health and medical research. The FDA already offers patients access to experimental drugs or medical devices outside of clinical trials via the Expanded Access (sometimes called Compassionate Care) program and approves the overwhelming majority of all applications received—about 99%. Under Expanded Access, the FDA continues to supervise administration of the experimental drugs which both helps reduce individual patient risk and works to improve overall public health outcomes.

The current “Right to Try” bill permits patients and their doctors to bypass the FDA and work directly with pharmaceutical companies for access to drugs which have merely completed Phase I clinical trials. Some patient groups argue that by cutting out FDA oversight and creating an alternative avenue for accessing experimental drugs, Right to Try actually increases patient risks and is demonstrably less safe than Expanded Access.

Over 75 patient groups sent a letter to the House opposing passage of the bill, citing the dangers it presented to patients such as the seven-day lagtime between patient access to the investigational therapies and FDA notification of any possible side effects or negative outcomes. Additionally, the patient groups cited the removal of FDA-sanctioned dosing and safety measures. They also cited shortcomings of the bill such as its failure to address significant barriers to patients such as access and cost.

The bill strips patients of potential legal remedies by protecting doctors and drug companies from liability in the case of negative outcomes for patients.

The legislation is also poised to compromise medical research and drug development by preventing the FDA from using any data from negative clinical outcomes in its drug-approval assessments. Barring FDA from using such data would shroud the successes or failures of the experimental drugs in obscurity—possibly preventing further large-scale advances in overall research and development.

Ultimately, “Right to Try” strips the FDA of established regulatory authority and protections, increases risk to patients, and obfuscates data and outcomes vital to continued success in research and development–all of which could result in serious, wide-ranging public health issues.

We at Contracts Associates will continue to monitor this important issue.

Sidestep FDA Form 483—And The Resulting Setbacks

Bringing a new drug or medical device to market is incredibly exciting for any sponsor. Ideally, you’d like the clinical trial phase to proceed without delays, so you can get your new drug to market quickly—and start helping patients.

The FDA can issue a Form 483 after an inspection where an investigator has observed conditions or issues at a facility that might constitute violations of the Food Drug and Cosmetic Act and serves to alert the organization’s management. As a best practice, if issued a 483, companies or research centers should respond in writing without delay. The response should include a corrective action plan addressing the violations which the organization should immediately implement. Failure to respond or failing to take remedial measures could result a Warning Letter being issued by the FDA, or cause delays in studies and development.

The FDA maintains a list of Inspectional Observation Summaries broken down by program area (biologics, bioresearch monitoring, drugs, devices, etc.) which can be found on the FDA website. By viewing this data, sponsors, clinical sites, CROs and IRBs have the opportunity to learn the most common reasons for 483 and how to avoid similar pitfalls during the clinical trial process.

For example, in the program area of Bioresearch Monitoring, 248 Form 483s were issued between 10/1/2016 and 9/30/2017. Common reasons for the 483 include:

• An investigation was not conducted in accordance with the signed statement of investigator and/or investigational plan (frequency: 140 times)
• Failure to prepare or maintain adequate and/or accurate case histories with respect to observations and data pertinent to the investigation and/or informed consent (76 times)
• Informed consent was not properly documented in that the written informed consent used in the study was not approved by the IRB and/or was not signed by the subject or the subject’s legally authorized representative at the time of consent and/or was not dated by the subject or the subject’s legally authorized representative at the time of consent. (14 times)

Stick to the plan

An investigational plan forms a roadmap for any clinical trial, giving a brief overview of the type and scale of the study. Mandated by the FDA, it’s the outline that gets a trial from start to finish: quickly and safely. Sponsors and investigators must either stick to this plan, properly amend it—or risk receiving a Form 483.

An investigational plan is detailed and thorough, but a sponsor won’t typically be on site to ensure it’s being followed. As such, it’s important to know that your contracts and terms with your CROs are solid and equitable. Failing to review contracts could leave you open to both liability and FDA delays. Our attorneys possess the necessary industry experience and a meticulous, efficient approach to contract reviews which means sponsors can be confident that they’re protected should an investigational plan go awry.

Let the record show everything

To gain the best results from a trial and to pass inspections, meticulous record keeping is a must. Much like an investigational plan, proper record keeping requires diligence and thoroughness. It involves preparing and maintaining case histories and taking detailed documentation at every stage, from observation to delivery. Failing to properly monitor and maintain records for a trial isn’t just a common reason for a Form 483, but can also compromise the study.

Contracts Associates will ensure that each sponsor/CRO agreement includes detailed language about monitoring and record keeping. The agreement is intended to protect the sponsor in the event your CRO fails to keep proper records. Working with us will allow sponsors to harness our knowledge and expertise, which means you won’t have to worry about this type of exposure.

Obtain informed consent

The FDA doesn’t just monitor the safety of publicly available drugs or devices. It also monitors the safety of clinical trial participants, and obtaining informed consent is a core element of that.

Sponsors must ensure trial participants know their rights in relation to a clinical trial they’re considering. This includes exposure to unknown risks, possible side effects, and potential outcomes. Ensuring that your study is compliant with FDA regulations about informed consent is crucial to keeping your company protected and ensuring your milestones are met.

Your in-house counsel might not have the time or manpower to carefully review a trial’s informed consent forms before signing off on them. The attorneys at Contracts Associates can provide the additional assistance you need, on an as-needed basis. We can help you stay on schedule and ensure compliance with informed consent requirements. There’s no better plan than to have informed consent contracts reviewed quickly and thoroughly by experienced industry professionals like us.

Implications of Form 483

It’s important to keep in mind that Form 483 does not constitute the final Agency determination of whether cited conditions are absolute violations of the FD&C Act. Form 483 is a factor for consideration, along with all evidence or documentation collected on-site, and any responses made by the company. Only then does the FDA make a final determination as to what future actions might be necessary.

Proactive approaches with Contracts Associates

At Contracts Associates, we work with sponsors to ensure their clinical trials don’t fall behind schedule or expose the company to undue risk. We can even produce and maintain a personalized “risk register” for you, complete with contract terms and other matters that we become aware of in our reviews—helping you avoid future problems.

Our extensive industry experience means we don’t require training—or the time, cost, and effort associated with a learning curve. We provide quick and meticulous turn-arounds, and can help you meet your milestones. Contact us today to find out how we can help you.