Public Review is Open for Comment: ICH Draft Revision of Guideline on General Trial Design and Conduct

The draft 2020 ICH(E8)R1 is three times the length of the original and is available for Sponsor comment. The ICH has taken its many years of data and identified principles which, among other things, will facilitate the acceptance of sponsor data worldwide, help ensure subject recruitment by involving subjects in study design and placing an emphasis on quality at every step of a trial.

Patient Input into Study Design

Patient organizations have already weighed in the updated Guideline reflects this critical input. Designing a study which fits the patients’ lifestyle (considering their disease state), will ensure that the drug itself will be better tailored to the population that will actually use the drug, post-approval.  From ICH(E8)(R1) 2.3:

“Involving patients at the early stage of study design is likely to increase trust in the study, facilitate recruitment, and promote adherence, which should continue throughout the duration of the study. Patients also provide their perspective of living with a condition, which contributes to the determination of endpoints that are meaningful to patients, selection of the right population, duration of the study, and use of the right comparators.”

Investigator Input into Study Design

ICH(E8)(R1) offers very early-stage study planning guidance and, not unexpectedly, it has found that reliance on just a few key opinion leaders for study design has to be augmented by opening the study to challenge by other subject matter experts: subjects and the potential investigators. From ICG(E8)(R1) 3.3.3:

“Clinical investigators and potential study subjects have valuable insights into the feasibility of enrolling subjects who meet proposed eligibility criteria, whether scheduled study visits and procedures may be overly burdensome and lead to early dropouts, and the general relevance of study endpoints and study settings to the targeted patient population”

Create a Sponsor Culture that Supports Open Dialogue

Interestingly, the ICH has identified a critical Sponsor success factor as “Establishing a Culture that Supports Open Dialogue” [ICH(E8)R1, 3.3] by rewarding team and individual critical thinking and encouraging open dialogue to go beyond “reliance on tools and checklists”. From the Guideline:

“Choose quality measures and performance indicators that are aligned with a proactive approach 169 to design. For example, an overemphasis on minimising the time to first patient enrolled may result in devoting too little time to identifying and preventing errors that matter through careful design.”

And:

“Study designs should be operationally feasible and avoid unnecessary complexity and unnecessary data collection. Patient consultation early in the study design process contributes to these factors and would be likely to result in fewer protocol amendments.”

Deemphasize Factors Such as First-Patient-In

The Guideline suggest that shifting team focus onto high-level quality goals in the planning stages, as opposed to micro-goals tied to enrolment, will contribute to overall study success:

“Choose quality measures and performance indicators that are aligned with a proactive approach to design. For example, an overemphasis on minimising the time to first patient enrolled may result in devoting too little time to identifying and preventing errors that matter through careful design.”

And:

“Consider whether nonessential activities may be eliminated from the study to simplify conduct, improve study efficiency, and target resources to critical areas.” [ICH(E8)(R1) 3.3.2]

Guidance on Operational Criteria

The Guideline provides Sponsor guidance to help achieve another critical success factor:  proactive, routine communication of changing study priorities and ongoing risks mitigation activities to its study sites, as site understanding of priorities and necessary resource allocation will enhance the correct implementation of a study protocol (ICH E8(R1). One possible solution would be implementation of sub-program management team, with an emphasis on crafting routine communication to update investigators on the changing study priorities (outside of the Protocol) and any operational issues such as drug availably, delays in safety reporting by other study sites and whatever else a sponsor may think a site needs to know to increase its investigators knowledge of the drug.

The draft is currently under public consultation. Stakeholders may submit comments or questions to step2comments@ich.org

Read the draft guideline here: https://bit.ly/2Jyzzjl

 

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.

More Clinical Trials in China in the Future?

The China Food and Drug Administration (CFDA), which became a regulatory member of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) in June 2017, is now moving forward with the implementation of several ICH guidelines in order to further the development of innovative drugs and devices in China, and align with global regulatory standards in manufacturing and development.

China’s implementation of the ICH guidelines will not only help ensure that global standards of quality and safety are met but can help reduce drag on pharmaceutical companies’ timelines by streamlining various processes such as clinical trial application and approval. Additional reforms will likely increase the number of Chinese hospitals and research centers able to manage clinical trials without having to undergo an extensive certification process.

These ICH-driven reforms will likely provide US pharmaceutical companies with greater opportunities to include China in global clinical research as well as greater access to the Chinese markets. As a member of ICH, China will be expected to continue implementing regulatory requirements for the manufacture and testing of study drug products. We expect to see an uptick in the conduct of clinical trials once the controls are in place to ensure that quality, safety, and efficiency is consistent across the Chinese markets.

We at Contracts Associates are looking forward to the further integration of China’s prominent researchers into our global clinical trials.