Why is a Study Start-up Management System the vital tool sponsors need?

By: LINEA System team

Countless industries are shifting to virtual and remote operations, and the realm of clinical trials is no exception. In fact, COVID-19 has only accelerated our industry’s dependence on technology to efficiently and successfully run trials. This shift has prompted the field to accept virtual or decentralized clinical trials as a trusted means to conduct research of such vital importance.

As teams become empowered to work from anywhere in the world, it is necessary for all stakeholders in a trial to have readily-available access to information on the clinical trial in real-time. The proper tools and technology to navigate a decentralized clinical trial ensures a successful outcome for the sponsor, and more importantly, an accelerated timeline for patients to gain access to life-changing medicines.

What is a Study Start-up Management System?

A Study Start-up Management System (SSMS) is an essential tool to efficiently accelerate clinical trial start-up. From all steps throughout the start-up process beginning with targeting the right sites, assessing site interest, conducting feasibility, collecting essential regulatory documents, obtaining approvals and contracts, and finally, enrolling patients, an SSMS ensures that a trial launches on-time and with the optimal sites.

There are three hallmark features of an SSMS:

  1. A built-in database of investigators. To deliver the optimal sites, every SSMS includes a built-in database of investigators.
  2. An automated workflow. By design, the system’s automated workflow enables a sponsor to quickly move from task to task and ensure that the start-up is progressing with no hold-ups.
  3. A cloud-based structure. The cloud-based nature of the system provides readily available access to data, metrics, and reporting anytime and anywhere.

Differing from other trial management software, an SSMS assists in the launch of a trial, while others such as a CTMS manage separate aspects of a trial after it has been launched and patients are being enrolled.

How can an SSMS help sponsors?

It is well-known that the most common source of delays to a trial is patient recruitment. This stems back to sponsors selecting initial sites that either prove unreliable once patients have been enrolled, or fail to enroll patients at all. In fact, according to the Tufts Center for the Study of Drug Development, 37 percent of sites selected under-enroll, and 11 percent fail to enroll a single patient. These routinely poor start-up metrics can lead to delayed trial timelines, and a 20 percent or higher increase in the originally projected trial budget.

When a sponsor selects the optimal sites first, patient recruitment is realized, the trial can proceed on-time, and the sponsor gains approval of vital medicines for patients in need. This efficient sequence of the events is possible using a Study Start-up Management System, with the built-in database of ranked investigators and an automated workflow to effectively launch the trial.

How does AcceleTrialdrive clinical trials forward?

AcceleTrial™ was created with the founding principle that nearly all clinical trials can avoid delays by selecting the right sites initially. Not only does AcceleTrial™ have a database of over 100,000 global expert investigators, those investigators are all ranked objectively. Its proprietary algorithm pulls hundreds of data points from multiple sources based on clinical expertise, access to patients, and former clinical trial experience, among other metrics. This powerful ranking system ensures that ultimately, the most effective and optimal investigators and sites are selected for the trial, thereby mitigating any chance of delay.

The “push and pull” workflow ensures a steady momentum, tracking each step and keeping the process seamless. To add transparency, both the sponsor and the sites and investigators are able to access the platform and complete their respective tasks while monitoring the full scope of the process. AcceleTrial™ is designed to be intuitive and make a significant and immediate impact on a trial’s launch time and operational costs.

When a trial progresses smoothly, the greatest value is the potential to make available life-changing medicines for patients who need them most.

COVID-19 & Clinical Trials: Understanding The Long-Term Impact

Like companies in all industry sectors, many biotechnology and pharmaceutical companies are struggling to understand and find strategies to address the challenges presented by the COVID-19 outbreak. For many, the impact of the pandemic on the conduct of clinical trials has forced both smaller biotechs and Big Pharma to make tough decisions to pause ongoing trials and reconsider timelines for data readouts, regulatory reviews, and product launches. Factors including impaired access to the healthcare system, travel restrictions, patient willingness to participate in trials, new guidance from regulatory agencies, and a shift in resources to fighting the pandemic are influencing the ability to advance many clinical research programs around the world. As companies focus on the immediate impact of COVID-19 on their development efforts, industry insiders are now starting to consider what the longer-term implications will be and how to address them.

The Life Sciences Practice at CRA recently reached out to a number of industry stakeholders, including regulatory and policy experts, venture capitalists, and contract research organizations (CROs), to better understand concerns about the impact of COVID-19 on clinical trials and how new challenges are likely to reverberate through the industry. Findings indicate that the impact on clinical development programs is already severe and will be broad and long-lasting, while the magnitude and nature of the impact will vary from trial to trial and company to company.

Addressing Short-Term Implications

In response to the pandemic, the FDA, EMA, and several national-level European governments have acted quickly to assess the impact and issued new recommendations related to clinical trials, including strategies for how companies can adapt to the current situation while reinforcing the essential need for any change to meet acceptable standards in patient safety and trial integrity. The agencies have also communicated their intention to remain flexible in evaluating protocol changes, deviations, and clinical efficacy and safety data. Industry insiders generally agree that the new guidelines provide a sufficient framework for trial sponsors to adapt their trial designs and protocols as needed at this stage.

As companies learn to adapt and consider implementing new strategies to keep clinical trials on track, in many cases the only option is to temporarily pause or delay development programs. For example, Provention Bio recently paused a Phase 3 trial in type 1 diabetes and Iveric Bio temporarily stopped a pivotal trial in geographic atrophy. But these decisions are not limited to smaller companies. Eli Lilly, Bristol-Myers Squibb, and Pfizer have announced pauses or delays in multiple development programs.

While consensus is that the impact of COVID-19 on clinical trials will be far-reaching, our analysis suggests that the level and duration of this impact will be especially severe in studies that have the following characteristics:

  • Enrolled vulnerable populations, including the elderly, the immunocompromised, and patients with pulmonary conditions (e.g., COPD)
  • Have primary or secondary endpoints that require in-person visits or hospital infrastructure and equipment (e.g., CT and PET scans) for assessment
  • Involve indications with minor safety or quality of life implications for patients (e.g., “lifestyle drugs”) and indications where a patient’s environment has a significant impact on therapeutic success (e.g., psychiatric and neurological indications)
  • Are currently in the patient recruitment stage or are in Phase 1 with healthy volunteers
  • Have trial sites located within hospitals or tertiary academic centers and in areas with high COVID-19 case density, potentially reducing the availability of staff to perform required activities and increasing the risk of adverse events and patient loss
  • Are evaluating immunosuppressive therapies or therapies that require complex and prolonged hospital visits (e.g., CAR-T cell and gene therapies)
  • Involve smaller patient populations where there are minimal margins of statistical power or people living with rare diseases (because patient accrual is already difficult, and the pandemic increases the risk for patient loss)

In the earliest stages of the pandemic, trial sponsors were primarily focused on essential decisions to pause or delay trials that were in the recruitment or pre-recruitment stages. Attention then shifted to trials in progress, where decisions related to protocols or timetables could have an impact on data integrity and statistical power.

The Longer-Term Impact

Looking ahead, organizations involved in clinical research are working to identify and assess financial, regulatory, and policy considerations that will affect their clinical programs in the longer term. Many are recognizing the need to plan for implementation of new and previously untried strategies to advance drug development programs.

In working to address the challenges of COVID-19, small biotechs could face potentially severe cash flow and financing issues as a result of trial delays. Companies with a single asset could be especially vulnerable. Delays in clinical trials may lead smaller companies to need additional funding at a time when their stock values have likely dropped and market conditions are not optimal. Many companies may be forced to make difficult cuts or prioritize development opportunities. Companies with potentially high-value products and platforms may be at risk of acquisition based on unfavorable terms.

Delays in clinical trials are likely to cause delays in projected launch timelines. This may in turn lead to shorter periods of patent exclusivity (barring patent term restoration) and lower near-term revenue forecasts. Changes in launch timelines also may shift the competitive landscape in many therapeutic areas, possibly presenting new opportunities for competitors that are able to adapt and act quickly in response.

From a regulatory standpoint, many stakeholders, including regulatory experts, trial site investigators, and CROs, anticipate that global agencies will require additional documentation and new protocols and procedures when considering new drug applications. The need for additional documentation can present significant challenges to trial sites and staffs. Processing this information also could cause delays in regulatory reviews and the ability of trial sponsors to quickly reply to follow-up inquiries from agencies.

Travel restrictions and social distancing measures will make protocol updates and deviations inevitable. Fortunately, per recent guidance from the FDA and EMA, trial sponsors will not be required to report protocol deviations prior to annual reports as long as the changes do not significantly impact the validity or safety of the trial. But sponsors and trial sites should meet with the appropriate institutional review boards (IRBs) to seek approval for protocol updates to reduce the risk that any changes could ultimately be rejected by the FDA or EMA.

The fact that trial participants cannot or will not attend in-person visits with investigators is a critical issue affecting many trials, but companies also should recognize the potential consequences if patients introduce COVID-19 to the trial itself. If patients contract the disease, it may impact clinical data by introducing elevated rates of related symptoms with a corresponding impact on endpoints. Any COVID-19-related fatalities would require these patients to be removed from data sets, potentially impacting the ability of trials to reach statistical significance. These consequences could be especially devastating for trials in rare diseases, where available patient populations are very small.

Based on our analysis, the impact of the pandemic on clinical trials will be felt on a policy level, including in drug pricing negotiations. The Pan-Canadian Pharmaceutical Alliance has already announced their intention to delay price negotiations for non-COVID-19 therapies. Pricing negotiations in Europe also could be impacted by the pandemic, especially for some non-COVID-19 therapies (e.g., the third or later drug to market in a class) where historically there has been a perception of low unmet need.

The Future

While most regulatory agencies have stated an intention to be flexible during these unprecedented times, it is critical that drug developers continue to monitor their risk diligently and develop contingency plans to adapt and respond to factors that affect their clinical development programs. Sponsors will need to balance patient safety, trial integrity, and statistical power considerations against funding and revenue issues on a trial-by-trial basis. In addition to reevaluating clinical development plans, companies may need to reassess their assumptions around pricing and revenue as well as the competitive landscape for both their pipeline and in-line products. There will not be a one-size-fits-all solution for the many short- and long-term challenges caused by COVID-19, but companies that are willing and able to rapidly adapt are likely to have the strongest chances for success.

Source: Clinical Leader

Clinical Trial Practitioners Begin Cautious Return to Work Sites

Leigh Burgess, MHA, MEd, MA, vice president of research operations for Dartmouth-Hitchcock Health, couldn’t wait to get back to her office after COVID-19 safety precautions forced her and most of her team to work remotely back in March.

Burgess has been able to work full-time onsite since mid-May, and says her facility has done a tremendous job of making everyone feel safe. Employees are screened before entering the office with a temperature check, there are sanitizing stations in place, all common areas are wiped down every two hours, and meetings are limited to 10 people with adequate social distancing.

“I feel safer here than I do at the grocery store,” Burgess says. That’s key, because “you want folks to feel comfortable,” she adds.

However, as a leader and manager, Burgess realizes her enthusiasm about returning to the office might not be universal. “Be a good listener and be open to adjusting” to each team member’s unique perspective, she advises.

For example, older personnel may understandably feel more vulnerable to getting COVID-19, or other personnel may have daycare issues or any number of challenging, extenuating circumstances to juggle if they can’t work from home. Don’t forget, some employees may be performing even better by working remotely.

Join Burgess Tuesday, June 23 at 12:00pm ET for a live Webinar exploring the considerations, processes, and procedures for research recovery and ramp-up related to COVID-19 and the impact it has had on research operation and administration. All Webinars are free for ACRP Members.

While she was already a fan of telecommuting, Burgess sees “a new openness” to the concept. She’s also been encouraged by how her team members and others have leveraged technology during this upheaval.

For those still mulling when and how to return to the office, Burgess stresses it’s never a one-size-fits-all solution, in part because of regional differences in the coronavirus’s impact. She also advises developing a three-month plan to reopen the office, rather than trying to focus efforts on a month-by-month basis.

Source: The Association of Clinical Research Professionals

Sites Struggle to Remain Solvent Amidst Trial Slowdown

Alarming economic news continues to pummel the clinical trial industry as more and more trials are stalled or even scrapped while industry tries to navigate its way through the COVID-19 pandemic.

Earlier this month, an ongoing quantitative survey conducted by Continuum Clinical in partnership with the Association of Clinical Research Professionals (ACRP) found 31% of clinical research study sites fear total closure as COVID-19-related stay-at-home orders and patient concerns over interacting with healthcare professionals continue to increase. Nearly 80% of sites indicated at least one of their current clinical trials had been put on hold or cancelled in recent weeks.

Even before the coronavirus hit, the clinical trial infrastructure was straining under a shorthanded workforce and tight financial margins. For example, 59% of sites in 2019 told the Society for Clinical Research Sites (SCRS) that they have only three months or less of operating cash.

Unfortunately, the dire news continues to pour in for beleaguered sites, according to an April 20 analysis of a global dataset covering more than 300,000 recruiting sites around the world by Phesi that found an “alarming” 10% spike in site suspensions in the past two months. “The timing aligns perfectly with the COVID-19” pandemic upending life in the U.S. and around the globe, says Phesi President Gen Li.

Sites are struggling and some are mulling or have gone ahead and furloughed some staff. The short- and long-term consequences will be negative and significant, says ACRP Executive Director Jim Kremidas. “In addition to putting highly qualified and valuable professionals on the shelf during a healthcare crisis, site cutbacks will make it very difficult for the industry to get back up and running as the impact of COVID-19 recedes,” Kremidas says.

The financial costs to a sponsor to replace a lost site is at least $30,000, Li estimates. In addition to the financial hit, time will be lost, typically three months or more, and possibly patient data and other trial results during the interim, he adds. “The situation is alarming and frankly has me concerned” for the clinical trial infrastructure, Li says.

And it’s not as simple as flipping an “on” switch to get a stalled trial back on track, Kremidas notes. “Learning a new trial protocol is akin to learning a new type of software,” he says. “It takes time to become familiar with both, and it’s easy to become rusty on both if you stop using them for any length of time,” he adds.

“Sponsors need to think about the financial stability of their clinical development supply chain, and sites are the most crucial link in it,” Kremidas says. “We urge sponsors, contract research organizations, and other interested parties to help us deliver educational resources now to help everyone operate more effectively throughout this difficult time, and to speed up restarting of trials once we’re past this crisis.”

In addition, ACRP joins SCRS’s call for sponsors to release site payment hold back funds during the crisis.

“There’s going to be a level of permanent damage,” Li says. “It’s up to us now to make it as small as possible.”

Source: The Association of Clinical Research Professionals

US clinical trial sites are most affected due to the Covid-19 pandemic

With the recent development of the current Covid-19 pandemic, there has been an increased urgency for both industry and non-industry sponsors to focus on finding a suitable therapeutic or vaccine for this highly contagious viral disease. In an effort to find a suitable treatment and prevention options for Covid-19 infection, more Covid-19 clinical trials are being planned and initiated, while a large number of clinical trials for non-Covid-19 indications are suffering delays.

With many regulatory agencies such as the FDA and EMA offering accelerated approval for Covid-19 therapeutics and vaccines, it could be in part that sponsors have shifted focus and research onto the current pandemic. But the majority of trial disruption could be attributed to patient safety, strict lockdown, social distancing, and the high demand for medical professionals to treat Covid-19 patients. High profile pharmaceutical companies have announced disruptions to planned and ongoing trials, postponing trial start dates and halting subject enrolment.

The Covid-19 Dashboard on the Pharma Intelligence Center dynamically tracks these disrupted trials from the Clinical Trials Database, along with the list of companies that are the sponsor, collaborator, or contract research organisation (CRO).

With over 1,000 trials being disrupted and more trials being added to this category daily, there is a direct impact on trial site activation and patient enrollment. Many of these sites are either being used for other purposes or are temporarily closed. With many countries enforcing strict lockdown measures, sponsors are unable to activate these sites, making it harder for existing trials to continue. According to GlobalData’s Clinical Trials Database, 56.1 % of disrupted trials are currently suspended while 20.7% are ongoing, but not recruiting any additional participants. When looking at site locations, the US had the highest number of disrupted trial sites at 66.1% followed by the UK at 12.8%, France at 9.3%, Spain at 6.5%, and Germany at 5.2%, as shown in Figure 1. According to the guidance of FDA and EMA procedures, many of these disrupted trial sites are now being repurposed for Covid-19 trials. Activation of new trial sites is usually not recommended for non-Covid-19-related trials unless no other solution exists for the ongoing trials. According to the EMA, “If there is an urgent need to open a new trial site for critical trial visits, for example outside the hospital, this may be implemented as an urgent safety measure (USM) first, followed later by a substantial amendment (SA) application for the approval and initiation of this additional site.” With the possibility of reallocating trial sites, there is also the need to move subject data such as medical records. In such cases, it is highly recommended from the EMA that this is done virtually and that any eCRFs can be adjusted accordingly to allow the receiving site to enter new data.

Due to site closures and lockdown measures, many companies involved in trial site management and coordination are feeling an economic hit. The top three countries with affected companies are the US, UK, and France. Contract research organisations are experiencing a hit too, with many organisations having to disrupt trials. According to GlobalData’s Clinical Trials Database, the top three CROs that are affected are IQVIA, Covance, and Sarah Cannon Research Institute. Among CROs, a statement from ICON highlights that 65% of their global sites are impacted in some way, which poses a period of financial uncertainty. Many companies are reviewing alternative approaches by using remote measures and virtual clinical trials, which aim to bring the study directly to the patient via online data collection and video call progress checks. It is important to note that with many countries easing lockdown, some trial sites may begin to reopen slowly to focus on other studies. With many companies shifting to alternative ways to conduct trials, it is possible that even after the Covid-19 pandemic the use of virtual trials will remain prominent.

Source: Clinical Trials Arena

Study Start-Up: Why You Really Need to Get This Right

You get one chance to initiate a clinical trial. Botch the start-up and you’ll expend great effort correcting course and playing catch-up. The waste of money and time — commodities that are chronically scarce among the biotech and specialty pharma companies that comprise most of our customer base — can be devastating.

That’s why we created a department that consolidates all the expertise needed to get trials off on the right foot. The underlying goal is to simplify by doing a lot of advance work and by setting sponsors up for success with a single contact throughout the start-up process, from country/site identification and regulatory, IRB, and EC submissions to site activation.

That way, our customers can focus more on science and less on … everything else.

The process actually starts before the study is even awarded, at the RFP stage. There’s no better time to hone our understanding of what’s important to the sponsor: first site initiated, first patient in, or whichever other goal is most relevant. Assessing large amounts of data at the pre-award stage is vital to putting the study on the right path and is indispensable in developing the contractual agreement post-award.

It’s a lot of effort on our investment dime, but the payoff can be considerable in a smoother study launch without the false starts and missteps that often result from absence of careful planning.

Once the study is awarded, it becomes the responsibility of a dedicated Project Launch Manager whose sole focus is effective and efficient start-up, laying the foundation for successful execution. All these PLMs do is start-up, and here’s why: Clinical trials typically last for years, and staffers who stay aboard a trial from start to finish lack the opportunity to develop the highly specific skills and disciplines that ensure an effective launch.

Having an itinerant launch crew that moves from trial to trial guarantees that every study gets our best start-up expertise.

Here are some other start-up recommendations we offer to current and prospective customers:

  • Set realistic timelines. Sponsors often have rigid timing for study milestones, and the clock starts as soon as the CRO contract is signed. But start-up is time-consuming, labor-intensive, and expensive, so it helps to establish realistic expectations — for example, allocating time for sites to negotiate nuances of the clinical trial agreement.
  • First things first. You should have a final protocol synopsis in place before initiating site identification. It will help you identify and qualify sites that have the necessary resources and experience. Recruiting effective sites and high-performing investigators helps ensure rapid recruitment and patient retention.
  • No stone unturned. Use all available resources to identify sites. Sponsor and CRO site databases are useful in cultivating and maintaining long-term relationships with high-performing sites. But if you’re searching for new sites and/or investigators within a specific geographic area or therapeutic area, you may need to look outside of your existing database.
  • Is everyone on board? In global studies, it’s critical to ensure that the study protocol is approved by the necessary regulatory authorities and ethics committees in every country where the study will be conducted. While we have moved toward a centralized approach for trial consistency and management, we believe in utilizing the local expertise on the ground as a way of maximizing success in each country.
  • Conduct a pre-study visit. It will help ensure that the objectives and expectations of the sponsor and CRO are aligned with those of the investigative site.
  • Monitor enrollment progress. Investigators often overestimate the number of patients they see with a certain condition, and that can hurt your feasibility study and recruitment projections. If you are falling behind on enrollment, be prepared to put significant resources into marketing the study to investigators, sites, and eligible study participants.

Source: Premier Research

Experts Predict COVID-19 Will Accelerate Modernization of Clinical Trials

The coronavirus disease 2019 (COVID-19) pandemic will lead to increasing adoption of artificial intelligence, automation, and virtual clinical trials, according to a prediction presented Thursday, during a virtual session of the Community Oncology Alliance 2020 Meeting.

“We really are in a place now to not lose momentum as we go through the pandemic, but in fact to accelerate it,” said presenter Howard Burris, III, MD, FACP, FASCO, president and chief medical officer of clinical operations at the Sarah Cannon Research Institute in Nashville, Tennessee.

The current systems of clinical trials have several challenges, including the sheer number of ongoing trials, handling rare mutations, limited patient access, and managing the amount of data. Solving these problems is vital to spreading clinical trials into community clinics, which Burris said is going to become increasingly important.

Before discussing these various challenges, Burris gave a brief overview of current trends in oncology clinical trials. Notably, Burris said the tumor agnostic approach, in which the biology of the tumor is more important than the site, has become more popular in recent years. There is also growing interest in plasma-based testing and increasing interest in FGFR inhibitors. While Burris said these FGFR inhibition was “troubling” a few years ago, he added that the FDA recently approved a second inhibitor, and that they are becoming increasingly understood, thanks to trials.

Additionally, Burris said physicians are ordering next generation sequencing-based gene panel testing for patients increasingly sooner to the time of diagnosis, which can have significant effects on patient participation in clinical trials. A large percentage of those tests are ordered for lung cancers and melanoma, according to data presented by Burris, but growing numbers are ordered for patients with head and neck, breast, and brain cancers.

In addition to the benefit for the patient, early testing can improve clinical research, drug development, and overall cancer research, Burris said.

“It is often the driving factor for participation in a clinical trial, knowing which drugs or which trials might be pertinent,” Burris said.

Earlier testing is one aspect of the effort to expand patient eligibility. Burris cited a recent analysis which found that expanding eligibility criteria enables more patients to participate, makes the trials more representative of the community and patients that physicians are seeing, and moves trials through the pipeline faster.

The data found that of 10,500 willing participants in a clinical trial, 5005 were excluded based on 1 or more of 3 traditional criteria. Instead of 5495 participants included based on traditional criteria, expanded criteria would have allowed 10346 participants to be included in the trial.

Finally, Burris said, there are infrastructure issues that must be addressed in order to expand clinical trials into community clinic environments. Facilities must invest in both necessary staff as well as systems in order to successfully handle clinical trials. Staff must include technical support, marketing support, regulatory experts, and safety experts, among others. Systems must also be implemented, including document management, molecular profiling, and clinical trial management.

E-consent form systems are also going to be increasingly important, Burris predicted, because they allow patients in more rural areas to consent without traveling to the facility.

“E-consent has been a huge satisfier for our many patients that are in outreach or rural sites, where we maybe have a physician visit once a week to provide care,” Burris said. “The need to travel and be in person will still happen, but that will be fewer and far between.”

All of these trends have been in effect for a while, Burris concluded, but he added that the COVID-19 pandemic will accelerate all of them.

“All in all, it’s just clear that this pandemic is paving the way, that we’re going to have the ability to, in fact, include more patients, include more practices, and include more physicians in participating in cancer research,” Burris said.

Source: Pharmacy Times