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Applied Clinical Trials May 2022

ACT's biennial Salary Survey takes a look at the future of industry following increased adaptation of decentralized technology 

Salary Survey: The Age of COVID

Emerging tools in data analytics, automation, EMR aggregation, and even social media are enabling faster and easier patient recruitment

Patient Recruitment Goes High-Tech

The Pulmonary Fibrosis Foundation (PFF) has developed new materials and tools for people living with pulmonary fibrosis (PF) to learn about and enroll in clinical research studies. The 

 provides comprehensive information on the types and phases of clinical trials, and how patients can participate.

The guide can be accessed by following the link above.

Articles

New guide provides comprehensive information on the types and phases of clinical trials, and how patients can participate.

Pulmonary Fibrosis Foundation Expands Clinical Trial Resources for Patients

Future Trials Forum: Decentralized, Direct to Patient and Clinical Research, Arena — 5/18-5/19

Events

Dr. Salim Idriss, Executive co-director of the Duke Pediatric and Congenital Heart Center & director of pediatric electrophysiology at Duke University Medical Center discusses a collaboration with the Cardiac Safety Research Consortium (CSRC), the FDA, and Duke University Medical school.

Podcasts

The Need For Pediatric Clinical Trials and Data

VIDA Diagnostics, Inc. has onboarded more than 1,000 sites globally in its VIDA network of imaging sites. This network is connected through the VIDA Intelligence Portal, a cloud native AI-enabled platform that drives efficiencies in clinical trial imaging operations by optimizing site recruitment and onboarding, staff training, image data collection, data quality, data curation, and more.

VIDA has onboarded more than 1,000 sites globally in its network of imaging sites.

VIDA Expands Site Network

, as Senior Vice President, Government Partnerships of Rho’s Federal Systems Division.

Syneos Health announced the promotions of 

 to President, Technology and Data Solutions, and 

 to Executive Vice President, Medical Affairs.

Greater Gift announces new board members, 

Clare Grace, Sharon Hanlon and Harsha Rajasimha

 has joined the company as Vice President of Clinical Operations.

 has joined the company as Head of China Development and Global Delivery.

Syneos Health announced the appointment of 

 as CEO and a member of the Company’s Board of Directors.

 has joined the company as executive vice president, global quality.

physIQ announced the appointment of two new members to its executive leadership team. 

 has been named Senior Vice President and General Manager of Life Sciences, and 

 joins the team as Vice President of Marketing.

 is the latest business to receive funding through the Industry Resilience and Diversification Fund.

 has received patent protection for their revolutionary ANID technology.

 announced that it is providing data, statistical analysis, and project management support for new research that will test the Moderna mRNA vaccine at more than 50 sites in South and East Africa.

 announced the release of its first Environmental, Social and Governance Report.

Northwestern University Feinberg School of Medicine Research Team:

Robert F. Kushner, MD, Alicia Agnoli, MD, MPH, MHS, Lesley Inker, MD, and Chi-yuan Hsu, MD, MS

The Herbert Pardes Clinical Research Excellence Award, was given to a research team from 

Northwestern University Feinberg School of Medicine

Once-Weekly Semaglutide in Adults with Overweight or Obesity.

 Two additional Distinguished Clinical Research Achievement Awards (one shared) were presented for their creativity, innovation, and novel approach that demonstrated immediate impact on the health and well-being of patients to 

University of California, Davis and to Tufts University School of Medicine

 was named the winner of a Silver Stevie Award in the Fastest Growing Company of the Year category in the 20th Annual American Business Awards.

The latest business and people happenings all in one place.

People and Business News — 5/22

Jill Wechsler is ACT's Washington Correspondent

Although FDA announced in Februarythat it was resuming “normal, routine domestic surveillance” of drug and medical product manufacturing facilities, many of the innovations and modifications for site inspections adopted during the COVID-19 pandemic will continue to play a visible role in agency compliance and enforcement operations. FDA’s Office of Regulatory Affairs (ORA) delayed or cancelled most on-site inspections during the past two years due to travel restrictions and infection concerns, but now seeks to resume active inspections where needed and practical.

This shift, however, does not signal an end to FDA’s wider use of paper document reviews and of virtual site visits, or remote interactive evaluations (RIEs), in ramping up oversight of biopharma manufacturing and research operations. These strategies notably reduced agency inspection costs, while enabling timely detection of compliance issues, and FDA sees value in continuing its expanded reliance on documents and records, on inspection reports from trusted regulatory authorities, and on wider use of remote real-time review of records and plant operations to provide assurance of proper manufacturing and clinical research operations.

Judith McMeekin, associate commissioner for regulatory affairs, pointed out during a presentation sponsored by the Alliance for a Stronger FDA on April 6 that ORA saved nearly $40,000 in 2020 and 2021, providing resources to develop a foreign travel planning system, expand personnel training, enhance information systems, and upgrade labs. FDA analysts are comparing the benefits and shortcomings of onsite inspections vs. record requests in order to develop criteria for revising or continuing these alternative practices.

More flexible inspection programs could gain from legislation before Congress to reauthorize FDA user fees and update agency operations and policies. The bill includes a provision to clarify FDA’s authority for collecting manufacturing records from medical device makers in advance or in lieu of field inspections and also for clinical study sites under the agency’s bioresearch monitoring program (FDA already has such authority for drugs). The measure also clarifies agency use of inspection findings of trusted foreign regulatory authorities in determining the need for preapproval inspections (PAIs). The bills requires FDA to post more information on the findings from drug and device inspections, such as warning letters and import alerts. And to expand unannounced FDA inspections of foreign drug establishments, the legislators propose a new pilot to increase such site visits and to evaluate the impact on both domestic and foreign facilities.

In response to these developments, FDA has worked to better explain its criteria for selecting and methods for conducting more remote and alternative facility assessments. At the recent FDA Generic Drugs Forum, staffers from the Office of Pharmaceutical Manufacturing Assessment (OPMA) in the Center for Drug Evaluation and Research (CDER)’s Office of Product Quality (OPQ) explained that FDA will weigh the need for an on-site inspection based on a risk-based assessment of product, process and facility risks.

 This involves scrutiny of records and other manufacturer information from trusted regulatory authorities.

Such information on a firm’s compliance history, process risks, manufacturing experience, and previous alerts, recalls, and complaints will help determine whether a PAI is needed or if FDA can assess the company’s capacity for risk mitigation and GMP compliance from company and regulator records. When FDA considers an RIE advisable, it will discuss the logistics, scope, and expectations with the manufacturer, request needed documents from the firm in advance, and outline its main questions or concerns and the logistics for conducting a remote facility tour. Such virtual site visits also can help all parties prepare for a future on-site inspection, if warranted, but do not qualify as formal inspections 

. They are voluntary for the company, but a refusal to cooperate with an RIE request can delay product approval.

OPMA Staff Fellow Alexander Gontcharov described an RIE for a foreign manufacturing facility utilizing a new unit of operation to produce delayed release tablets and capsules. This involved four three-hour sessions with a facility “walk-through” using a laptop on a cart with external cameras and microphones. Another RIE for a new unit producing new ointments and liquid products had three four-hour sessions that used a portable tablet PC with Wi-Fi connections. FDA investigators viewed warehouses, labs, and production areas, as well as document control systems. Inspection findings may be specified in a close-out memo, or FDA may later send a letter identifying difficulties found at the facility and if an on-site inspection is needed.

The shift to remote assessments is reflected in the rise of warning letters that involve alternative inspection tools, according to the 2021 annual report from CDER’s Office of Compliance (OC).

 While FDA exercised enforcement discretion in multiple cases to avoid shortages of critical medicines, OC reports a rise in drug adulteration warning letters based on sample testing and on information from records requests. In addition, OC conducted more than 45 remote regulatory assessments (RRAs) of clinical sites under the agency’s biomedical research compliance program. An FDA draft guidance published in April 2021 advises manufacturers on how the agency seeks to conduct this growing range of remote evaluations.

Overall, FDA advises manufacturers to recognize the importance of RIEs and to query about any unclear agency information requests. While FDA recognizes that RIEs are not equivalent to full inspections and that the agency only can see what the firm makes available, these alternative tools have cut the need for on-site PAIs in half and helped the agency meet user fee approval goals for 90% of applications this past year.

https://www.fda.gov/news-events/press-announcements/fda-roundup-february-4-2022

https://www.fda.gov/media/150036/download

https://energycommerce.house.gov/sites/democrats.energycommerce.house.gov/files/documents/Section%20by%20Section_The%20Food%20and%20Drug%20Amendments%20of%202022_5.4.2022.pdf

https://sbiaevents.com/files2022/GDF-2022-Agenda.pdf

https://www.fda.gov/media/157954/download

https://www.fda.gov/news-events/press-announcements/fda-provides-guidance-remote-interactive-evaluations-oversight-drug-facilities-during-covid-19?utm_medium=email&utm_source=govdelivery

Plan to keep new methods adopted during COVID in place.

FDA to Continue Inspection Efficiencies After Pandemic

VIDA Diagnostics, Inc. is introducing a new suite of retrospective data analysis services for clinical trial sponsors in response to growing demand for precision data to optimize lung treatment trials.

Suite of retrospective data analysis services for clinical trial sponsors created in response to growing demand for precision data in lung treatment trials.

VIDA Introduces New AI-Enabled Biomarker Services

Legal Executive, Clinical Research Malaysia

Legal Assistant, Clinical Research Malaysia

A Clinical Trial Agreement (CTA) as defined in The Malaysian Guideline for Good Clinical Practice is “a written, dated, and signed agreement between two or more involved parties that sets out any arrangements on delegation and distribution of tasks and obligations and, if appropriate, on financial matters. The protocol may serve as the basis of a contract.”

Review and negotiation of a CTA is an important process as it affects the trial activities conducted at site since the study or trial could not commence without any CTA in place. In 2015, the Clinical Research Malaysia (CRM) Legal & Regulatory Affairs Department developed its Clinical Trial Agreement System (CTA System) to provide a systematic and efficient way to review, as well as speed up the CTA process. This CTA System is an online platform where all the CTA(s) for the Malaysian Ministry of Health sites are submitted by sponsors and CROs.

The CTA System was launched in March 2016 and since then, all the negotiation, review, approval, and endorsement of the CTA are conducted via the CTA System, which features automatic alerts to CRM Legal to review. The total number of CTAs that have been reviewed via CTA System is illustrated below featuring a total of 562. Currently, there are 180 sponsors, 49 CROs who are registered under the CTA system, who are in charge of negotiating the CTA terms and conditions, as well as the study budget with the site.

Sponsors and CROs can keep track of CTA status from the day of study registration until completion. The system offers transparency of the collaboration of work between the sponsor/CROs and CRM’s Legal & Finance department as all the correspondences and communication are held within the system.

The CTA System enables the CRM Legal & Regulatory Affairs department to keep track of studies by accessing ‘New’ & ‘Review’ tabs for the studies which are still in the reviewing process, and the ‘Settled’ tab for the studies which have been endorsed by the reviewer. Registered users can also transfer and handover a specific study from a previously registered clinical research assistant to the new appointed clinical research assistant, which provides a seamless flow of information. This assignment and changes of the study is still subject to the approval of the registered user of the study in the CTA System. Another alert feature prompts a notification via-email when a user has given a comment in the platform, allowing all parties to be aware of changes or a need to act.

Prior to the system’s implementation, from 2012 to 2015, the CRM Legal & Regulatory Affairs department took an average of 59 days to review CTA until endorsement.

 Since the system’s implementation, CTA review has been expedited only 14 days.

When there are any activities that involve data interchange, secure data management should be a top priority. With CTA System authentication and encryption methods, a secure data management protects parties involved in the CTA negotiation from data losses, thefts, and breaches. Strong data security ensures that critical CRM and clinical research assistant data is backed up daily and retrievable in the event that the primary source fails. The CTA system provides a safe, centralized site for data collection and storage, as the clinical research assistant provides some confidential data in the CTA system for the purpose of CTA review, such as the study protocol, study budget, and so on. All data entered into the CTA system is backed up in the backup system, which serves as a risk mitigation measure in the event of a system failure. Apart from the foregoing, the CTA system has a function that allows the study CTA information to be quickly retrieved. The CRA can find any previous CTA submissions by searching the Protocol ID or NMRR ID of the study. The same applies to CRM Legal.

In fact, CRM has gone a step further in terms of CTA review by recognizing the CTA system as a single source of operational truth, allowing all audit processes to run smoothly because all communication and data are saved and stored in proper tabs with specified dates and times. In addition, the essential data in the CTA system can be collected and organized at the corporate level through CRM Legal and Finance as departments to better track CRM's key performance indicator.

To conclude, CRM’s investment into an efficient and well-ordered collaborative Clinical Trial Agreement System serves to encourage sponsors and CROs to do more clinical trials in Malaysia.

 is a Senior Legal Executive of Clinical Research Malaysia

National Pharmaceutical Regulatory Agency (NPRA) Ministry of Health Malaysia. Malaysian Guideline for Good Clinical Practice (Fourth Edition). Glossary 1.21. pg 10. 2018.

https://clinicalresearch.my/evolution-of-clinical-trial-agreement/

How Clinical Research Malaysia sped up CTA turnaround using a web-based system.

Managing Clinical Trial Agreements 

Most people are pretty careful about what to believe on their social media feed, but do they apply the same care to their internet surveys at work? It’s an important issue. The clinical trials industry uses internet surveys for competitor analysis, customer satisfaction/feedback, or even to measure patient outcomes. Internet surveys are ubiquitous and overwhelming so it is easy to respond carelessly.

The purpose of this blog is to describe what careless responding is and how we can avoid and identify careless responses.

Careless responding refers to survey responses that are random or do not reflect the degree to which the construct is present in the respondent. Carelessness is increased when there is a lot of surveys, or when surveys are forced on us, not relevant to us, or force us to respond to items for which we have no opinion. (Boto et al. 12/21 ACT;Duamis & Raymond, 12/21 ACT; Galwicki ACT 11/11). Careless responding can be due to inattention (either partial or complete), fatigue, time pressure, or socially desirable responding. Careless responding is common, varying between 3% to 50%, depending on the context. Measurement problems begin to occur with as little as 10% careless responding (Meade and Craig 2012). The technical consequences of careless responding includes decreasing the reliability of measures, obscure validity, and increase the risk of Type 2 error.

Recommendations: Survey construction and sampling

Make your surveys short (Dillman et al. 2009).

Instructions have a small but significant impact

Instructed response items. (e.g. Fill in a 3 for response.’ Ward 2015)

Self-reported items - directly asking respondents at the end of the survey whether they think their survey responses are of adequate quality for use in the study Ward (2015). “... self-report alone is not sufficient to identify careless responses.” (Meade & Craig p.8)

Sample only those potential respondents for whom the survey will be relevant. Not only will this increase your response rate but also reduce careless responding, although you still may get people who want to peruse the survey to get information on your project.

Don’t use forced responses unless you are sure the question is relevant and the respondent has the information. Still, if they don’t want to give you that information, you should let them progress through the survey.

Recommendations: Analytic procedures to detect careless responding

response times—either long or short. Meade and Craig 2012 did not find an association between time and careless responding.

Conclusion—don’t believe everything you read on the internet

The clinical trials must rely on internet if it is to remain responsive to industry changes and patient needs.

The clinical trials industry is being impeded by noisy data from careless responding on internet surveys

Identifying careless responding to improve survey construction and results.

Improving Your Survey Data

Scott Gray is the Co-founder and CEO of 

The average investment in recruiting just one patient for a clinical trial has been 

 to be as much as $6,500. Once patients are successfully enrolled, clinical trial coordinators then face the uphill battle of retaining these patients for the duration of the study. With dropout rates often exceeding 30%, the loss of trial participants is a significant concern for our industry.

Fortunately, hope is not lost—pharmaceutical sponsors and clinical research organizations (CROs) are finding they can improve patient retention rates and bolster trial completion with patient centric trials and patient support services.

Understanding the many barriers preventing patients from trial participation is most essential step to keeping them enrolled. These challenges often include missed work (and subsequent loss of income), complex travel arrangements, time away from home and family, increased childcare needs, and the financial burden of delayed reimbursements. Factors such as the trial duration and a patient's perceived feelings of being valued throughout the trial also impact retention.

Maintaining open and ongoing communication between trial participants, caregivers, and trial staff go a long way in increasing retention rates. Initial, one-on-one discussions help patients anticipate the scope and commitment involved in trial participation while demonstrating the level of support provided throughout the study to overcome potential challenges.

Improving trial outcomes with patient centricity

In recent years, our industry has made a noticeable and advantageous shift towards “patient centricity.” Patient-centric clinical trials improve the patient experience by making trials as comfortable and efficient as possible and removing unnecessary burdens to patients facing a difficult diagnosis. These trials consider the patient's needs from the earliest planning stages, incorporating a patient-first blueprint into the study's design.

In February 2022, the Food and Drug Administration (FDA) released new 

 detailing how drug development teams can implement patient-centric trials. An earlier 

 by The Economist Intelligence Unit found drugs developed with patient-centric processes were:

Nearly 20 percent more likely to launch than drugs developed without a patient-focused approach. This number was consistent across therapeutic areas (neurology, oncology, and rare diseases).

Quicker to recruit 100 participants (4-month time period) compared to other innovation types (6-11 months) and all trials (7 months).

A patient-centric approach makes sense socially, financially, and clinically and is rightfully becoming a standard practice throughout our industry. To improve patient experience, clinical trial teams can assist patients with study logistics, leverage technology to reduce patient visits (i.e., wearable monitors, video appointments, etc.), and establish communication channels to keep patients and trial staff well-connected throughout the entire process. From trial design through trial completion, prioritizing patient needs ensures better outcomes for patients and ultimately brings treatments to market faster.

Initially, when trial teams began using a patient-centric model, they focused on improving the clinical aspects of trials, focusing on providing better patient care. It quickly became apparent that addressing patients' social needs were equally crucial to trial success.

CROs and trial sponsors began asking: How can these studies help patients beyond treatment? Are patients struggling with daily pressures, like finding transportation to and from trial appointments? Are pressures from out-of-pocket expenses causing patients to consider dropping out? The answers to these questions highlighted the need to help patients manage the daily challenges of trial participation.

Today, many clinical trial sponsors look to companies like 

 to manage patient logistics for their trials. Clincierge’s global team of patient coordinators works directly with patients and their caregivers to ensure comfort and safety throughout a trial. Coordinators are local to the patient, ensuring they share a time zone and cultural understanding and providing a high-touch, concierge level of service.

Throughout the duration of a trial, patient care coordinators establish trusting relationships with patients, caregivers, and clinical site staff. Being regionally and culturally aligned from enrollment through the last visit, patients feel they have someone 'in their corner.' This consistency supports better long-term trial retention as patients and caregivers can focus on the patient's treatment, not the logistics involved. It also frees clinical site teams to focus on the data collection and endpoints of the trial and the patient experience during the site visits.

Patient support providers can also alleviate the complexities of multi-country rare disease trials, which often require extensive travel, visas, relocation, language translation, housing, and transport of medically fragile and pediatric patients. Patient coordinators often plan and pre-pay for cross-border travel while navigating the bureaucratic obstacles preventing patients from participating.

In ideal cases, trial sponsors build patient support into the earliest rounds of the trial design, allowing patient coordinators to assist with patient onboarding. This trial model also encourages patient diversity. By communicating with underserved populations and educating them about available compensation and travel reimbursements, patient coordinators assist in enrolling patients who fit trial criteria regardless of their ability to cover participation costs.

By partnering with a patient support services company, clinical trial sponsors ensure higher retention rates while focusing on the needs of the patients involved. Ultimately, patient-centric clinical trials help new therapies get to market faster while supporting the pharmaceutical industry's most significant goal—caring for the health and well-being of patients around the globe.

Case study: Patient support services at work

A review of a multi-year clinical study highlights the impact patient care coordinators have on trial outcomes. The study is researching a new treatment for Duchenne Muscular Dystrophy (DMD), a rare progressive muscle-wasting disease primarily impacting boys.

In rare diseases like DMD, patient populations tend to be small and geographically distributed across the globe. The DMD study spans 35 trial sites in nine countries. Over a five-year period, 18 patient care coordinators have provided support services, including arranging cross-border travel and accommodations for more than 170 trial patients and their caregivers.

These coordinators arrange cross-border transport and accommodation for patients and help them feel comfortable surrounded by new cultures. Speaking the native language of the patient and caregiver and living in the same time zone ensures ongoing communication and personalized support throughout the trial.

Site travel has been provided via airplane, rail, and wheelchair-accessible car service. In total, patient care coordinators booked more than200 airline flights, 250 ground transportation trips, and 530 hotel reservations.

Over 1,300 reimbursements have been distributed to participants after site visits.

Patient carecoordinators have learned the intricacies of DMD to anticipate this patient population's needs and travel preferences. DMD patients often require wheelchairs, so they need ADA-compliant hotel rooms, accessible bathrooms, and living spaces allowing for wheelchair movement.

Likewise, because chewing and swallowing are challenges for DMD patients, many require specific foods and strategically planned mealtimes. Patient coordinators ensure safe and fortified foods are available, allowing patients to adhere to strict dietary guidelines. As patients' medical needs have changed throughout the trial, coordinators continue to tailor logistics to accommodate them.

Removing the emotional, financial, and logistical burdens of clinical trial participation allows patients, caregivers, and trial teams to focus on life-changing treatments. Although this trial is still underway, it is progressing on schedule and within budget, due in part to a patient retention rate that surpasses industry benchmarks.

 is the founder and CEO of Clincierge. He was featured on a previous episode of the Applied Clinical Trials podcast. Listen 

Sponsors can ensure higher retention by partnering with patient support services.

Featured Content

Applied Clinical Trials May 2022

Salary Survey: The Age of COVID

Patient Recruitment Goes High-Tech