Fred Gebhart

	Newspaper ads, radio and television, posters, fliers, and other conventional patient recruitment strategies don’t seem to work, producing familiar and depressing results. “Many patient recruitment companies are feeding patients into a system that does not work very well,” said Paul Wicks, PhD, Vice President of Innovation at PatientsLikeMe.com, a patient community website that partners with trial sponsors to boost enrollment. “In today’s world, it is about trial participation, not trial recruitment. The confluence of technology and patient engagement can upgrade the clinical trial experience and outcome.”

	The clinical trial process relies on a triad of stakeholders: patients, investigators, and trial sponsors/CROs. No single entity controls all three corners of the trial triangle and connecting the stakeholders is increasingly difficult. But a growing number of providers are adapting 21st century web-based and mobile tools to connect the corners, boost trial participation, and speed trial completion.

	Which tools are most appropriate? It depends on the audience. 

	“As technology advances, it needs to be utilized to connect with patients,” said Joan Chambers, Chief Operating Officer of clinical trials information publisher CenterWatch. “Email, Twitter, Facebook, patient communities all have their place. But you can’t forget that you still have patient populations that are not so tech savvy. You can’t forget the traditional channels, but they are certainly less useful.”

	CenterWatch plays a central role in web-based electronic recruitment even though it does no direct patient recruitment. The company translates and transforms the wealth of trial recruitment information published at ClinicalTrials.gov into language that is understandable by nonclinical audiences. 

	“Our goal is to help CROs, patient recruiters, study centers and study sponsors get as much patient exposure as possible for their trials,” Chambers said. “There is no sign that patients as a whole are getting more likely to enroll in trials, but some trials are meeting their enrollment goals on time or even early by connecting more directly with patients. We are all looking for new models and strategies to provide better trial information to the patient community to meet sponsor enrollment goals.”

	Other providers see the opportunity on the investigator side. DrugDev.org matches trial sponsors/CROs with would-be investigators and adds site management services to strengthen industry links.

	“Sponsors always assumed that investigators would be there, but finding qualified investigators who are also interested is not that simple,” said CEO Ibraheem Mahmood. “We are able to deliver investigators very quickly who are qualified and enthusiastic about the protocol. That investigator enthusiasm has a significant impact on successful patient recruitment.” 

	PrincipalInvestigators.com is another company building a global database of investigators. Would-be investigators register their clinical background and interests, trial experience, location, and availability; sponsors search the database for likely matches and post their trial needs. 

	“We outsource investigator recruitment for CROs,” said Marketing Manager Mike Dziurkawski in Poland. “We offer an alternative solution for CROs that would rather focus on their own core strengths. We can provide a pool of investigators that is both deeper and more geographically diverse than any single sponsor or CRO.”

	But the more obvious opportunity is linking patients with sponsors. The basic strategy is to target patients who are most likely to be appropriate for the trial and motivated to participate.  

	Some programs target health care providers, usually clinicians and hospitals, by mining electronic health records to identify specific patient populations. But most would-be recruiters are going directly to patients. Some are CROs seeking to expand their service offerings by creating or partnering with online patient communities. And others are patient communities seeking to enhance treatment options by partnering with trial sponsors. Then there are information brokers seeking to link patient communities with trial sponsors/CROs. 

	Direct access to patients likely to qualify for trials as well as access to rich population data are key factors in all three business models. Patient communities self-select for specific conditions, are highly engaged, highly motivated to share information, and eager to advance treatment.

	“The fundamental problem is finding the right patients for your trial,” said Brian Loew, CEO of Inspire, a private company that links patient support and advocacy groups with trial sponsors. “Online patient communities have given us an important piece of the puzzle. People in a community are more pre-disposed to participate in a trial than a random population of patients.”

	Bringing patient communities into trial recruitment and retention is hardly new. HIV/AIDS groups broke down the doors of the clinical trial community in the 1980s and hundreds of disease-specific groups have followed. Breast cancer, autism, diabetes, asthma-pick a disease and there is almost certainly a patient advocacy group searching for better medicines, or a cure. Bringing more effective treatments to market faster is in patients’ own best interest. 

	“We want to see progress in trials and treatments brought to market earlier,” said Diane Gross, MPH, National Program Director for the Lupus Research Institute (LRI). “Lack of enrollment in trials means slower results. People with lupus need new treatments now. Anything we can do to move development along is our mission.”

	How advocacy groups move development varies dramatically. The Michael J. Fox Foundation leverages its founder’s star status to build awareness for Parkinson’s as well as channel research funding. The Foundation also launched the Fox Trial Finder to give patients and caregivers a direct link to Parkinson’s trials that are currently recruiting. LRI and other advocacy groups use similar tactics, including disease fairs to provide face-to-face information and reach patients who may not have access to or use web-based technologies.

	Jeri Burtchell blogged her multiple sclerosis trial experience and developed Partners in Research, a web-based community to share MS information and experiences and promote trial participation. An MS trial algorithm on the home page helps community members decide whether or not they should consider a trial. Except for patients who are well controlled and tolerate their current medication well, the answer is almost always yes. 

	“Patients and trial sponsors need to be brought into the 21st century,” Burtchell said. “Patients stand to gain or lose the most in research, but the reality is that you trust another patient before you trust an ad on TV or a pitch from pharma. Patient communities are the trusted resource that can bridge the gap, translate pharma speak into real language, and bring the patient perspective to trial sponsors.”

	CROs are seeing similar value in bringing patients, and the patient perspective, to their trial sponsor clients. 

	“Patients are the most underutilized resource in the entire healthcare system because the traditional channels used to interact with them were created before the digital era,” said John Reese, Senior Director, Health Engagement and Communication, for Quintiles. “In the United States, 90% of patients never hear about a clinical trial in their lifetime. We are trying to reach those 90%, using digital channels to educate and energize patients who are already empowered to improve their health through social media, patient communities and information sharing.”

	Quintiles created patient communities based on medication safety resources (MediGuard.org) and trial resources for specific diseases (ClinicalResearch.com). Patients and caregivers received qualified medical information and updates, Quintiles and its clients get de-identified patient data for population studies, and personal information that can be used to target trial participation offers. Reese said a recent COPD study enrolled its first patient in six minutes and completed enrollment in six weeks.

	Other CROs are using social media and data mining to identify and contact potential trial participants. In 2013, PPD acquired Acurian, an electronic patient recruitment and retention firm, to help meet recruitment goals for its clients’ trials and support their strategies for data-driven feasibility, site selection and enrollment delivery. Acurian can tap a database of more than 70 million households that includes self-reported disease information and medical data and reach out to patients directly via email, social media and other online techniques.

	“We still do some radio and TV recruitment, but it is seen as less cost-efficient,” said Rick Malcom, Executive Vice President and General Manager of Acurian. “Web-based activities have become increasingly important for patient recruitment and retention. But there is no one technique that is going to resolve every recruitment and enrollment challenge. Many people are potentially interested in trials. But it is very hard to make people aware that a trial is happening five miles away without specialized help.”

Articles

A growing number of providers are adapting 21st century web-based and mobile tools to connect the corners, boost trial participation, and speed trial completion.

New Technologies Close the Recruitment Gap

Editor’s Note: This article is part of a series examining popular peer-reviewed articles from years past called “Peer-Reviews Revisited: Why You Should Read Today.” You can read the other articles in this series 

Recruiting patients remains one of the most difficult challenges clinical trial sponsors face. Recognizing that fewer than five percent of eligible adult patients enroll in therapeutic trials, many sponsors have turned to supplemental recruitment, the practice of pre-qualifying community-based patients for referral to clinical trial sites for screening.

“The primary reason that patients do not participate is that they are unaware of opportunities to do so,” said Elisa Cascade, MBA, Vice President of Corporate Development at DrugDev.org, an online network designed to link trial sponsors and investigators. “Physician investigator sites and other researches are actively seeking opportunities to make community-based patients aware of clinical trials. There was little information in the literature on patient-level interest in studies and patient characteristics associated with study interest.”

 of nearly 8,600 patients that focused on drivers of patient interest in clinical trial participation. The study was conducted by Quintiles, where she was Vice President, Digital Patient Unit. The survey identified three key variables that explain patient interest in studies, age, condition, and treatment satisfaction.

Patients age 65 and over are less interested in trial participation than patients under 40 (odds ratio 0.549, p=0.03).

Patients dissatisfied with their current medications are more interested in studies (OR=2.105, p=0.0015).

Compared to patients with cardiovascular disease or diabetes, those with cancer (OR=0.56, p=0.0097) and gastrointestinal diseases (OR=0.414, p=.0420) are less interested in study participation.

“These findings have important implications for the clinical trial recruitment plan,” Ms. Cascade said. “Investigators who tailor their recruitment strategies to patients who are younger and have a greater dissatisfaction witdh their current treatment (due to bothersome side effects or unmet treatment need) should see a better return on investment for their patient outreach activities.”

Recruiting patients remains one of the most difficult challenges clinical trial sponsors face.

Top Reasons Patients Join Clinical Trials

Functional service provider arrangements, or FSPs, are evolving beyond the clinical data management tasks they were designed to streamline. FSP models can offer trial sponsors cost savings of 30 to 50 percent by reducing infrastructure and overhead expenditures. These outsourcing arrangements can also bring strategic and operational benefits.

As attractive as FSPs can be, outsourcing is not a panacea. Most FSPs hit a performance plateau about 18 months after implementation. Challenges in scaling up operations, inadequate resourcing, suboptimal resource utilization, quality control and general operational fatigue can jeopardize performance, delivery, and quality as mistrust and doubts grow. 

“If the FSP is to be successfully navigated across the plateau, the point at which significant operational issues begin to surface, the partners must press forward in good faith, relying on each other’s experience and expertise toward effective operationalization of services” said Theo Erasmus, MS, Chief Executive Officer of South Africa-based CROs ClinData International and ClinVet International. 

The former Vice President, Global Functional Resourcing (Biometrics) for Quintiles was lead author on a 

paper outlining strategies to conquer the FSP plateau

. The authors outlined specific interventions to power the FSP partnership into long-term success:

Strong and experienced FSP leadership that is designed to be scalable with growth.

Alignment of sponsor and FSP goals and expectations early in the partnership.

Sponsor buy-in and support at all levels from the C-suite down.

A clear governance and communications plan that specifies how and when issues will be escalated.

A strong focus on projects and project management.

The use of both retrospective and prospective metrics to track progress.

“The benefits of FSP arrangements ensure they will continue in popularity as long as the FSP can break through the 18-month plateau,” he said. “CROs need to take a proactive role to optimize productivity and quality while continuing to keep costs under control.”

Functional service provider arrangements, or FSPs, are evolving beyond the clinical data management tasks they were designed to streamline.

Power Past the Plateau to FSP Success

	In an article that sets the stage for why improvements in the contract negotiations with sites has and needed to improve for the past two years.

	Managing clinical trial agreements and the agreement negotiation process can be an important source of delay and additional cost in any trial process.

	“Clinical trial agreements influence the costs of a sponsor of a clinical trial in several ways,” said Myrthe Rijswijk-Trompert, CEO and Senior Legal Consultant, Salvius Legal, Zeist, The Netherlands. “A poorly drafted and/or negotiated agreement can create legal risk exposure (and) unexpected financial liabilities. Inefficiencies in negotiation can result in unnecessary additional costs. Troublesome negotiations may delay a clinical trial and delay the marketing of the investigational drug, resulting in severe loss of profit for a sponsor.”

 found that nine percent of respondents identified specific damage resulting from poorly negotiated trial site agreements. More than six percent said their firm had been involved in legal actions in which a clinical trial agreement was key.

	A third of respondents named communications skills as a key problem area in trial agreement negotiations. Most respondents (80 percent) said prior bad experiences with a site influences decisions on whether to work with that site in the future. Key causes of delays include:

		Insufficient country- and industry-specific knowledge by one or both parties.

		Lack of internal resources and qualified staff or failure to use appropriate external resources and experts.

		Confusing and unclear site agreement templates.

		Failure to use certified translators with experience in the clinical trials industry.

	“Contract negotiations with hospitals and investigators are time-intensive, however there are many opportunities to make the negotiation process more efficient and maintain a proper risk and quality standard,” Ms. Rijswijk-Trompert said.  Improving clinical trial agreement negotiations is an opportunity to be seized.”

An article that sets the stage for why improvements in the contract negotiations with sites has and needed to improve for the past two years.

Better Contract Negotiations Improve Trial Efficiency

The 2010 Patient Protection and Affordable Care Act authorized the creation of the Patient-Centered Outcomes Research Institute. PCORI underscored existing trends toward increasingly individualized and personalized medical care, and required research protocols to include various subpopulations such as racial and ethnic minorities, women, age, and comorbidities, genetic and molecular subtypes, and quality of life preferences.

“This requirement presents the potential to discover and disseminate crucial comparative effectiveness research findings that individual patients and their clinicians need for making informed health-care decisions,” said Kathleen Wyrwich, PhD, Senior Research Leader at Evidera Outcomes Research Group, Bethesda, MD. Dr. Wyrwich is also lead author of an examination of “Personalized Healthcare” 

 based on a panel discussion at the International Society for Pharmacoeconomics and Outcomes Research annual meeting in 2011.

“Healthcare providers and systems know race, ethnicity, sex, age, comorbidity status, and other relevant information for patients,” she added. “A more holistic definition of precision or personalized healthcare can now be considered, the promise of knowing which interventions are most effective for which patients and under what circumstances. [It] also incorporates the personal needs, preferences, healthcare access, and adherence attributes that each person brings to the healthcare encounter in addition to genomic information.”

Discussants offered key perspectives on the need for and development of personalized medicine.

Subgroup effectiveness is already part of routine oncology care. Information derived from subgroup analysis is affecting patient care by changing therapeutic choices.

About two-thirds of all drugs currently in the development pipeline have an associated biomarker. Personalization and more precise delivery of care is already built into these product development programs. 

Generics have become the standard of care for many diseases. Trial sponsors must identify and target subpopulations that are less than optimally responsive to existing agents or may be at increased risk due to specific genetic, molecular, or other individual factors.

PCORI underscored existing trends toward increasingly individualized and personalized medical care...

Moving Toward Personalized Healthcare

Pharmacovigilance is the next frontier for outsourcing in the pharmaceutical and biologics industry. In an era when effective pharmacovigilance during the clinical trial process can make the difference between success and failure for product licensing applications, outsourcing can be a vital step in the regulatory approval process.

“Traditional thinking suggests it is essential that pharmaceutical and biotechnology companies exercise complete control over their pharmacovigilance activities,” 

, MD, Chief Executive Officer of industry consultants Prism Ideas in the United Kingdom. “Successful experiences of outsourcing other clinical activities are making outsourcing of safety services to specialized service providers a more attractive solution.”

The concept of pharmacovigilance is familiar, Dr. Sawyer said, but the practice has become a complex web of international standards and local requirements that can vary by jurisdiction. The International Conference on Harmonization and the Council for International Organizations of Medical Sciences guidelines describe the broad scope of pharmacovigilance. Regulatory requirements by the European Medicines Agency (EU), the Food and Drug Administration (US) and similar bodies set market-specific practices. It can be far more effective in terms of regulatory success and resource utilization to hire outside expertise than to develop and maintain in-house capabilities.

Outsourcing pharmacovigilance offers key advantages:

As-needed access to specialists with the skills, technology and scale needed for specific programs and projects.

Strategic planning and resources that enable projects to be launched more quickly and efficiently.

Unblinding by the provider rather than the sponsor encourages more effective documentation and reporting of suspected unexpected serious adverse reactions.

Independent, outside review of existing practices and procedures can radically improve efficiency, cost and speed of internal operations.

“The advantages of outsourcing a clear,” Dr. Sawyer said. “Utilizing the services of a specialist provider will benefit the manufacturer by defining and validating a drug’s safety profile and accelerating the delivery of new therapies to the marketplace.”

Pharmacovigilance is the next frontier for outsourcing in the pharmaceutical and biologics industry.