Pat i e n t

R e c r u i t m e n t & R e t e n t i o n 1 0 1 :

How to Thrive in Today’s Recruitment & Retention Landscape

Part 1: The Recruitment & Retention Landscape 1. Metrics – Where are we today?……………… 2. Protocol Design……………………………………

Part 2: Recruitment Strategies 3. 3 Recruitment Strategies for Trials Today…

Part 3: Retention Planning 4. Keys to Retention Planning……………………

Part 4: Key Takeaways for Sponsors & CROs 5. Key Takeaways…………………………………….

About this E-book:

With the globalization of clinical trials rapidly expanding, the

industry’s practices are shifting. Despite the many tools and techniques available, patient recruitment around the globe continues to cause expensive

delays in the majority of clinical trials.

In this e-book, we examine the patient recruitment landscape

today and outline what you can do to improve your success

with recruitment and retention.

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PATIENT RECRUITMENT AND RETENTION 101

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Part 1:

The Recruitment & Retention Landscape

Since 1991, countless editorials have attempted to describe how poor recruitment can hamper clinical research. Problems with patient recruitment have proven to be among the top reasons for the failure of clinical trials. However, there have not been any credible comprehensive overviews of the topic.

Every other link in the clinical trials chain has been described using standard monographs, including planning, design, conduct, analysis, interpretation, and publication – every link except, patient recruitment.

Despite the incomplete picture, it is evident that the current recruitment landscape is one of the industry’s most significant areas for concern.

Chapter 1: Metrics – Where Are We Today?

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When you look at the industry’s data, it quickly becomes evident that the patient recruitment landscape is failing to perform its duty: to educate patients and bring them into studies. As a result, the majority of recruitment investments fail to pay off.

$2.9 billion was spent in 2009 on patient recruitment. Of that, the majority of the investment was

most likely lost due to unsuccessful execution based on the following statistics:

Where Are the Dollars Going?

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Dr. Wolfgang Eglmeier – Problems in Recruitment & Retention, March 23, 2011

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Dr. Wolfgang Eglmeier – Problems in Recruitment & Retention, March 23, 2011

The retention side of the equation is experiencing a similar disappointment. On average, 25% of patients fail to complete a trial once they’ve registered. Additionally, average attrition rates are trending at about 30% and increasing.

The implications of these statistics result in hefty expenses. As the recruitment and retention landscape continues to underperform, these unfruitful investments lead to delayed trials, increased expenses, and overall frustration.

Each day a drug is delayed to market, sponsors can lose up to $8 million!

In addition to delays to marketing, with retention levels where they are in the industry, valuable data is often lost. The cost to replace patient data is extremely high, and can significantly add to your costs. Additionally, the lack of patient data may yield the study outcomes obsolete as not enough data is obtained to have statistical importance.

PATIENT RECRUITMENT AND RETENTION 101

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These unfortunate trends of recruitment and retention have been relatively consistent around the globe and across different scenarios. Across the board, site success is indicative of unfruitful patient recruitment investments. Studies show that about half of all patients recruited are recruited by 15-20% of sites, and 80% are recruited by the top 40-50% of sites.

It is important to note that recruitment strategists are not to blame. These frightful statistics are not a result of poor planning, but statistical laws based on the results of modeling. Historically, the clinical research industry has modeled clinical trials in silos instead of using more appropriate, cross-functional teams. For example, protocol design and development typically is only looked at from a “pure” scientific perspective. The challenge this presents is the practicality of successfully operationalizing the protocol as designed at the site level and, ultimately, at the patient level.

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Dr. Wolfgang Eglmeier – Problems in Recruitment & Retention, March 23, 2011

PATIENT RECRUITMENT AND RETENTION 101

Half of all patients recruited are recruited by 15-20% of sites.”

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Protocol design determines the accessibility of the target population. Oftentimes, sponsors fail to consider recruitment challenges during the protocol design and development phase. By considering potential enrollment obstacles, the sponsor can help keep recruitment on target. As a result, this limits the need for protocol amendments and/or addition of more sites down the road.

With recent advances in technologies and science, it is only natural that the nature of the industry becomes more complex. The patient recruitment landscape is a rapidly evolving creature.

It is vital that your team works to develop a model that allows for flexibility over the course of the trial.

Thankfully, we have laid out four areas to consider during protocol design that will prepare you for recruitment challenges, and provide you with the flexibility necessary to navigate today’s market.

CHAPTER 2: Protocol Design

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1. FDA requirements to advance science

Longer study participation periods

Increase in the number of required procedures

More study visits before and during the trial

Increase in targeted patients

2. Availability of patient population: This needs to be strategically and realistically evaluated at the start of protocol design.

Does the target population exist as defined by the study criteria?

What are the referral patterns?

How do individuals become educated about a clinical trial opportunity?

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Consider at Protocol Design:

PATIENT RECRUITMENT AND RETENTION 101

3. Costly Solutions: What options will you have lined up?

Additional sites – an additional site will cost, on average, $20-$30K in the United States.

Protocol amendments – these will cost, on average, $1M.

4. Protocol Support: There is no guarantee that these solutions will be effective without the proper support in place.

Evaluate the site’s understanding of the study design and program offered to support enrollment. Are they bought-in to the resources made available?

Evaluate the site structure and experience. Do they have established referral and patient identification pathways?

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Case Study Situation DAC Patient Recruitment Services (www.dacprs.com) recently embarked on a recruitment journey for a clinical trial on Lysosomal Acid Lipase (LAL) Deficiency. At the time we joined, the study was working with four sites, eight patients, and a 3-month enrollment duration.

Challenges Throughout the industry, there has been a lack of specific LAL education among physicians. LAL is an under-recognized disease among physicians and, therefore, under-diagnosed. As a result, the study was dealing with an extremely limited patient population due to the rarity of the disease (1 in 100,000 in the United States). It was difficult to identify and evaluate the protocol design to determine if the target population was available and how to reach them.

Solution As this patient population is predominantly pediatric patients, the target audience was the parent. Most parents are extreme activists for their children. Therefore, they reach out and participate in patient advocacy and support groups for LAL or Wolman disease. This coupled with the disease being under-recognized among physicians led to the development of an educational program targeting advocacy and support groups as well as potential referring physicians. Both groups were targeted equally to build overall awareness of the disease and the symptoms to consider.

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Part 2:

Recruitment Strategies

CHAPTER 3: 3 Recruitment Solutions for Trials Today

Over the years of modernized clinical trials, a number of basic techniques have repeatedly led to successful patient recruitment. Techniques such as educational materials and patient identification toolkits have proved to be effective. These basic information sources are important, and should not be overlooked when developing a recruitment strategy.

However, in recent years, the realm of ‘successful patient recruitment strategies’ has vastly expanded. New technology allows for recruitment professionals to be more creative and targeted in their approach to seek out more qualified individuals. The industry now has access to a wide range of techniques that are quickly proving to be indispensable, and are becoming standard practices. Here are three successful solutions for patient recruitment in today’s arena.

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1. Social Media Considered the modern day “word-of-mouth,” social media presents a unique opportunity to spread the word in a quick and cost-effective manner. Platforms such as Facebook, YouTube and online social communities present great opportunities for identifying individuals who are seeking options or for others to share their experiences. Social media also allows for geo-targeted campaigns to focus your efforts only on logistically sound targets.

With social media comes a number of legal questions as the industry works to define the regulations around this medium. Always be sure to speak with your recruitment provider to understand the boundaries of this medium.

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3 Recruitment Solutions

for Today’s Trials

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Take advantage of the modern day “word-of-mouth” to maximize trial recruitment.

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2. Study Website

Study websites are quickly becoming a preferred component of clinical trials across the globe. These websites present an unmatched opportunity to provide relevant information to a highly engaged population. Individuals will come to your study website for the sole purpose of learning about your trial for themselves or a loved one. This population is extremely engaged and motivated. When designing your website, be sure to capitalize on this engagement using various calls-to-action. This will move the individual further down the pipeline. For tips, check out our recent blog post on the secret to a successful study website.

A study website allows you to provide more information than most other recruitment options. Websites provide more landscape for text, and more options for engagement. They also allow you to link to other credible or supporting organizations’ websites. Oftentimes study websites will include an online pre-screener. This allows for easy access and an immediate response for the participant. If a study website is something you’re interested in, we strongly recommend using pay-per-click advertising and search-engine optimization (SEO) to market your website and drive traffic to it. Typically, potential patients are not going to enter your website URL to directly access the site – you need to real them in.

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Study Website Implementation Considerations: Study websites are no light investment. Before pursuing a website there a certain items to consider. • Length of enrollment and regulatory approval timelines. Websites typically take 8-10 weeks to develop.

Regulatory approval can take from 2 days up to 3 months depending on the use of central IRBs, local IRBs and/or ethics committees. Therefore, it could take a minimum of 3 months to launch a website. If your study has a 6 month enrollment timeline and involves a large percentage of sites that use local IRBs and/or involves multiple countries, you’ll want to evaluate the impact of instituting a website.

• Countries involved. Most recruitment strategies are accepted from a regulatory perspective worldwide, but cultural acceptance varies. Central and Western Europe are typically more receptive to study websites, while Eastern Europe and the Baltic Region are not as receptive. This is an important consideration when evaluating the use of a study website. Culturally, if the use of a website is not an accepted practice within a particular country, then one would not invest the time or money in developing and seeking approval of this strategy.

*Recently, DAC signed an exclusive partnership with Remedy Health Media. This 12-month partnership provides our clients with unmatched access to the most engaged online communities. To learn more about the opportunities available to you, you can read the press release or listen to our podcast interview with Dennis Upah, Executive Vice President at Remedy.

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3. Pharmacy Outreach This is a strategy that has grown in popularity over the last couple of years due to the ability of being highly “prescriptive” in identifying potential study participants as it correlates to inclusion and exclusion study criteria as well as targeted geographies. Pharmacy outreach is one of the most targeted direct-to-patient outreach approaches you can consider in supporting your recruitment program, which will positively impact your overall retention. Due to the targeted nature of this strategy, response and referral rates typically are 28% and 13% higher than traditional outreach (i.e., direct mail campaigns), respectively.

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Pharmacy outreach is one of the most targeted, direct-to-patient approaches.”

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Part 3:

Retention Planning

CHAPTER 4: Keys to Retention Planning

While a tailored patient recruitment strategy is necessary to start a trial off on the right track, it is also vital to be mindful of your plan to keep these patients engaged once recruitment efforts take off. Retention starts when the first patient is enrolled into the study. Often, sponsors wait too long to consider retention, and find themselves trying to make up for lost time. As a result, attrition rates and costs skyrocket.

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Hopefully you understand that retention planning must be part of the initial study design to avoid costs and delays down the road. In this chapter, we will tell you how to plan for retention and define various keys to success.

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Remember that patient retention starts with the first patient enrolled! The following guidelines will help you set timelines to get your retention plan off to a great start. • Know your IRB/EC and each country’s guidelines. From here, you can backtrack to determine the

starting point for planning.

• Establish a line item for retention in each study budget. Consider allocating 5% of site per patient grants for retention. • 90% of sites have no formal plan/funds to address retention – don’t get caught in this trap! It

is also important to increase your allocation based on the therapeutic indication or length of the study.

• Provide a site training and support continuum. Successful retention programs start with site buy-in. Be sure to provide ample time and resources to educate and engage your sites. Part of this training is to ensure that sites understand the patients’ motivators and deterrents.

• Keep the “Appreciation for Participation” top-of-mind with every study participant and caregiver.

When to Plan

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Developing a program that offers the level of information an individual seeks, as well as an ongoing dialogue that meets their expectations if they choose to participate in a trial is two-thirds of the trial. It is essential to consider the expectations of clinical trial patients when developing a retention plan. Here are some patient expectations to consider:

2/3 of the Challenge

PATIENT RECRUITMENT AND RETENTION 101

• Explanation of potential side effects It is important to the patient to feel educated and aware of the situation they are getting into.

• Access to the PI at every visit

• Reimbursement of travel/parking expenses Transportation assistance packages have shown a reduction of attrition by 45+% and LTFU less than 7%.

• Opportunities to meet other participants

• A supportive website just for study participants A mobile app has shown to reduce attrition by 45+% and LTFU less than 7%.

• A mechanism to tell friends about the study

• Progress reports and lab results Patients expect to know how they are responding to the study. They will want to feel involved in the success of the study.

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6 Keys to Retention Success

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There is a large body of literature and study participant surveys that provide detailed information and can help define a successful retention program. The literature supports that trial participants want to be informed and receive ongoing information and education about their disease and diagnosis. They desire this information to make a decision to participate in clinical trials, and the continued desire for ongoing information is needed to create that “sense” of being part of something bigger. Their contribution does count and makes a significant difference in the lives of others through the advancement of science. In layman’s terms, think about trial participants as consumers. And, think about all the information we expect to have at our fingertips when it comes to purchasing a service or product. Trial participants are one and the same. The following six elements provide the right formula for a successful retention program: 1. Understand, Educate, and Inform the Patient. Take the time needed to talk to the patient

and their caregiver about the requirements of the trial and what they are committing to. Ensure the sites have the right tools necessary to educate the patients and their caregivers about the study. Tools should include those that remain at the site for reoccurring use as well as take-home materials. Successful retention greatly depends on the relationships that the research staff forges with the patients. The sooner trust is established, the more likely patients will feel a sense of commitment to the trial.

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6 Keys to Retention Success

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2. Appeal to the Patient’s Needs. Surveys show that patients want to receive ongoing education about their disease state. This can be established through the distribution of patient newsletters, brochures, etc.

3. Motivate the Patient to Participate. There are a number of reasons people choose to participant in clinical trials. Understanding these motivations can help enhance study engagement and compliance. For example, one motivator is receiving care from a specialist who, otherwise, may not be available. In this instance, the research staff wants to ensure that the PI spends quality time with his/her patients.

4. Offer Unprecedented Care and Attention. Ensure enough time is allocated for each patient visit with all research staff needed. Provide contact information for patients to connect with study staff throughout the trial period. Responses to all calls should happen within 24 hours.

5. Show Explicit Appreciation. This can be accomplished by sending motivational text messages or holiday, birthday, and thank-you cards. Just a simple note can express appreciation for their continued commitment and participation in the study.

6. Demonstrate the Value of Their Contribution. Maintain ongoing communication with the trial participants and follow through with what you tell them you will do.

PATIENT RECRUITMENT AND RETENTION 101

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It was imperative that a proactive retention campaign be implemented to offset this projected attrition. DAC provided study support materials to assist in fostering and maintaining a long-term relationship with the patient, as well as branded patient support items to keep the study top-of-mind. The receipt of educational and support items throughout the trial provided a sense of “belonging” to the study participants. They felt they were part of something important and not just volunteers. This helped them feel invested in the overall program.

As a direct result, attrition rates trended no higher than 10% throughout the trial.

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Case Study: Alzheimer’s Retention Program

PATIENT RECRUITMENT AND RETENTION 101

DAC Patient Recruitment Services recently worked on a mild-to-moderate Alzheimer’s retention program over a 12-month time period. We worked with 70 sites and 930 patients across nine countries. Due to the known short-term side effects of the compound, the sponsor projected a 35% attrition rate.

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As society embraces technological advances in communication, we have seen an upsurge in the number of study participants and/or caregivers who have and use mobile technology. Worldwide, there are 4.55 billion mobile users and 1.75 billion smartphone users. And it’s predicted that smartphone subscriptions will increase to 5.6 billion users by 2019, covering 90% of the world’s population. Maintaining retention rates in a trial is just if not more important than hitting the enrollment goals. Without data to support statistical analysis, the trial itself becomes a mute point. The use of text messages to maintain patient engagement and compliance while reducing administrative burden at the site level is taking off in full force. Ninety-eight percent of all text messages are read within 15 minutes of receipt. You know that the intended messages reach patients. Even with the high read rate, there are a few points of consideration when determining if text messaging is the right strategy for your retention program. Points to Consider:

• Therapeutic Area Does the disease indication lend itself to acceptance of text messages for visit reminders? For example, for an oncology study you may consider using a more traditional, personal approach with visit reminder calls versus an automated text messaging system.

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Text Messaging to Improve Retention

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• Age of Participant As with the disease indication, you’ll want to take into account the age of the participant and if there is caregiver involvement. For example, it may not be prudent to send text messages to an Alzheimer’s patient. However, it may be perfectly plausible to send them to the caregiver, who is mostly likely familiar with texting.

• Length of Enrollment Period; Number of visits Text messaging is more cost effective for studies with a higher number of visits. Much like cost efficiencies achieved when you print higher quantities versus smaller quantities, the higher the number of visits required in a study the greater the cost savings.

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Test messaging is more cost effective for studies with a higher number of visits.”

• Mobile Technology Penetration in Participating Countries While the adaptation of mobile technology is strong across more prominent countries, there are still some regions with low penetration rates. It’s important to understand what these penetration rates look like, as it will dictate the overall adoption of this technology solution among the participating research centers and their patients.

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Part 4:

Key Takeaways for Sponsors and CROs

Here are four key action items to take to your next recruitment discussion. Above all else, remember that each patient is valuable and should be treated as such.

CHAPTER 5: Key Takeaways

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1. Protocol Design Patient recruitment and retention starts at protocol design. Be sure to engage clinical operations as well as your partners and recruitment specialists. A challenge for you to consider would be to engage a potential patient as part of your protocol review team.

2. Evaluate the Patient Population Determine your available patients based on protocol criteria. It is a highly competitive landscape thanks to competing studies and resources. Only once you have a clear picture of who you will be targeting, can you begin to plan for recruitment and retention.

3. Proactive vs. Retroactive Planning Proactive planning can save your trial millions in future expenses by limiting the addition of new sites, protocol amendments, and replaced patients, and costly delays.

4. Establish a Line Item in Each Study Budget The recruitment cost per patient can vary from $1,500 to $10,000+, based on indication, length of study, and study requirements. Consider allocating at least 5% of site per patient grants for retention.

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Melynda Geurts

Vice President of Operations

DAC Patient Recruitment Services

Melynda is a 22-year DAC veteran with expertise that spans protocol planning, recruitment and retention, global regulations, emerging markets, and more. She was instrumental in DAC’s rise from a niche SMO to a global recruitment and retention leader, and is a driving force in the company’s approach to project operations, site management, contract negotiations, and business development. Melynda is a 2008 inductee into the PharmaVoice 100 Most Inspiring People in the Life-Sciences.

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About the Author

PATIENT RECRUITMENT AND RETENTION 101

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If you’re interested in speaking with our recruitment and retention specialists, contact us today!

recruit@dacprs.com

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