spacer
home > > summer 2010 > trial boosters
PUBLICATIONS


Trial Boosters

Graham Wylie of the Medical Research Network provides a model for effective implementation of support tools and techniques to boost patient recruitment and retention in clinical trials

The recruitment and retention of patients are widely held to be the two most critical targets in the quest to speed up clinical trials. Recruitment is essential as it remains the period in a trial most able to deliver significant savings in study durations, if a solution is found. Retention is also of great importance because reducing drop-outs leads to decreased variance, fewer patients needing to be randomised and more patients reaching the end of therapy periods. Combining the two delivers significant time and cost savings in a clinical trial. This article discusses the breadth of solutions that aim to have an impact on recruitment and retention, and how to assess which may be the best to use.

WHY BOTHER?

Over the last 20 years, several methods have been developed to ensure recruitment targets are met. Back in the 1980s, the pharmaceutical industry introduced ‘competitive enrolment’, where more sites than were strictly necessary were initiated in a study, enrolling patients in competition with each other instead of meeting fixed targets. This is certainly effective, but can be expensive as it requires considerably more sites to be initiated, many of which will recruit poorly and yet can still be as much as a third of the cost of a reasonably performing site. It also increases variance as block sizes have to be small, thus allowing the potential for variation between sites to increase. There is no doubt that competitive enrolment is a great approach, but increasing recruitment per site can be a much more effective tool that will also reduce cost and variance. Models of improvement produced by such services demonstrate that reductions in the trial recruitment period of 20 per cent or more across a whole trial can be produced. These models are derived from metrics showing services such as home trial support (where nurses undertake trial visits in the patient’s own home) can increase recruitment by at least 50 per cent and halve drop-out rates, speeding up the entire trial, even if only implemented in 50 per cent of sites. The metrics also demonstrate that the use of advertising across all sites can drive recruitment increases of up to 20 per cent. Used in conjunction with each other and competitive enrolment, tools of this nature can yield very significant overall benefits.

THE MARKET PLACE

Although the tools and techniques to improve recruitment and retention have been available for at least the last 10 years, the market is still quite immature, characterised by a low number of established service providers as well as a rapidly increasing number of new tools and companies, most of which are in the early stages of development. Services offered by companies can be categorised as follows:

  • PR, advertising and media
  • Software – feasibility, administrative and brokerage
  • Training
  • Strategic consulting
  • Resourcing
  • Reducing the trial’s impact on patients’ lives

PR, Advertising and Media Services
These companies focus on communication with patients or referring health professionals, to inform them about the trial and encourage them to engage with it. They also look at the reaction of patients to therapies and trials to see where they would be best placed to get the most participants.

Software Services and Products
These basically fit into three types – those that allow sites to assess their patient database to determine who might fit the protocol (feasibility), those that are designed to support the site with budgets, invoices, patient payments and so on (administrative) and those that are designed to bring together patients, sites and sponsors (all of whom register with the websites) as a brokerage service.

Training Services
Companies focus on training by providing education to all site staff about trials and how to take part effectively and efficiently, ensuring understanding of the rules, increasing compliance and raising quality. Sites can become certified, as can the staff. Training is also targeted at sponsors and CROs in a multitude of ways.

Strategic Consulting
Services tend to be offered by traditional consultancy companies, giving general business and process advice to sites to ensure they run their trials well and build a quality brand. Purchasers are usually large sites that already feel they have a reputation to maintain and wish to be more efficient in the way they deal with trials, achieving greater consistency of performance across therapeutic area groups and increasing their attractiveness to sponsors.

Resourcing Services
These focus on providing support to sites by ensuring that they have enough staff with the right skills to provide the maximum possible recruitment in a site. They can provide all types of staff, but typically focus on study site coordinators, database managers and nurses.

Services that Reduce the Impact of the Trial on the Patients’ Lives
These companies focus on making it easier for the patient to take part in the trial, and cover a broad range of services – for example by reducing the drain of the patient’s time of participation in the study, or through using debit card points and rewards systems for patients for payment of expenses or indeed fees in some cases.

ISSUE & SOLUTION MAP

Implementing these tools is no guarantee of success, leading us to ask why this may be the case. Clearly each tool can be effective in the right circumstances, but we have found success only comes when the team targets the most fundamental level of issue for solutions first, moving on to more complex issues and solutions once the more fundamental level is dealt with (see Figure 1). To support such an analysis we use a tool to organise solutions into a hierarchy for implementation, mapping solutions against them trial by trial.

Each of these solutions addresses specific issues. We can map the issues to solutions as follows:

Restrictive Protocol
Protocols are not always something that can be easily changed, although in reality it is often possible to relax inclusion or exclusion criteria to a degree without compromising the scientific integrity of the study. Furthermore, trials are often hugely demanding on patients, for example with multiple visits, infusions and training, but can be made less demanding and more appealing with various levels of support. The solution is to amend the protocol and/or offer some trial visits in the home or other types of patient support to reduce the burden on the patients, which will increase patient consent rates significantly.

Site is Inadequately Resourced
This may be because a site is new to research but interesting to the sponsor, who may be attempting to increase drug awareness or to access previously untapped patient populations. In more experienced sites, a lack of resource may still be an issue, sometimes invisible even to the PI, as the site nurses will generally only recruit the number of patients they know they can comfortably handle. The solution in all these cases is to add expert resources to the site.

Patients do not Flow through an Established Referral Process
Patients may be inherently rare because the drug is for a condition that has had no previous therapy, or causes significant changes to the therapy treatment pathway, or which has no specific specialist associated with it and so presents too many different specialists. A good example is the introduction of the first treatment regimes for early rheumatoid arthritis (RA) 20 years ago. New therapies of that time worked best when used early in the disease, but traditionally specialists only saw patients later, once symptomatic therapy was no longer effective. No referral pathways existed for early RA patients, so these had to be created. Similarily, new symptomatic therapies for endstage cancer patients of any type need to access a whole host of specialists who may see these patients, such as pain clinics, surgeons, oncologists, haematologists, general practioners, gynaecologists and geriatricians, where referral paths are not otherwise common. The solution is to build and maintain new referral pathways within and between sites, as well as a web presence to increase awareness.

Patients Do Not Attend At All
Although superficially similar to the issue above, here there is an added dimension, where the condition is in fact common but the patients do not seek treatment, as no therapy has previously been available. A good example is male pattern baldness, which, prior to recent therapies, was not really treatable and was not a serious inconvenience to most sufferers. When therapies came along, reaching these patients was hard as they were not presenting themselves to the healthcare system. Similar situations occur when a trial requires a high number of newly diagnosed patients with a condition which has a high background incidence and thus where general screening of the population would provide increased referrals. The solution here is to use advertising aimed directly at patients and for screening programmes.

In any given trial, the issues will be different in importance and detail. Mapping out the issues using this approach allows the project team to be confident that they have the complete list which are then placed on the hierarchy of solutions described in Figure 1, to ensure focus on the most basic first. As an illustration, there are many studies where the patient potential is high and the protocol is not unusually constraining, but recruitment is still poor. Often site resources are the issue, and once supplied, recruitment may return to target levels. In some cases however, that will still not be enough, such as in the male pattern baldness example mentioned earlier, which may require advertising directly to the patients to boost enrolment. The key point here is that advertising is needed but cannot be effective if the exclusion criteria are too tight or the sites do not have the resources in place to deal with the patients when referred.

SOLUTION PLANNING

Ensuring solutions are cost-effective is complex; based on how widespread the issue may be, the cost of the fix, the time to set up the fix and the delay in determining if it should be implemented. This has to be balanced against the risk of delaying the project and the probability of the solution not actually working. Adding to this complexity, it is evident from the examples above that some issues apply to whole trials – advertising for male pattern baldness for example – whereas others are more country- or even site-dependent. The challenge of reaching into every site to determine the best approach is not insignificant, yet the payback can be well worth the effort, especially where it prevents a solution being implemented in sites that do not need it, but which might benefit more from an alternative.

In an effort to control costs, trials often have recruitment contingency plans put in place, but justifying such plans in clinical trials can be difficult. This can be illustrated by setting up a thought experiment with two scenarios – in a hypothetical study with a 12 month recruitment period where recruitment is assessed after three months. In scenario A, recruitment is trailing at 75 per cent of the target and complex and expensive solutions are being considered for implementation in half the sites. If these take three months to initiate, the sites with the new services will have to increase recruitment from their present low rate by roughly 75 per cent to meet the original timeline for the study. In scenario B, recruitment is trailing by 10 per cent and low cost solutions are being considered that take one month to initiate and can be applied to all sites. Now the increase in recruitment rate in all sites will have to be 17 per cent. For either scenario, recouping the cost of the solution can usually be achieved only by finishing the trial earlier than originally planned and thus reducing the total study running costs. Implementing after three months leaves scenario A almost no chance of achieving this, and given that sources consistently quote that at least 50 to 80 per cent of all trials suffer significant delays, it is hard to justify that this sort of solution be left to a contingency. For scenario B however, if the extra costs are relatively low and confidence in achieving increased recruitment of 17 per cent is high, one could wait to see if a solution is necessary before implementation – although still not for long.

We can conclude that the best way of containing the cost of any solution is not by waiting to implement them, but applying them at the start of the study in a small number of sites in order to achieve the speed up desired with the minimum cost.

CONSULTATION

Given that contingency plans are not often cost-effective but upfront planning of solutions against target sites can be cost neutral, or save money by speeding up the study, we recommend detailed upfront planning during a consultative phase with the project team.

Once the solutions are in place and recruitment is underway, within a short period of time – usually less than 25 per cent of the way through the recruitment period planned – site performance should be evaluated. This will allow sufficient time for recruitment of supporting tools and methods to be implemented in new sites with enough time left in the recruitment phase for the benefits to be felt. At this stage, sites not performing well usually need a site visit. It may be that the resourcing at the site initially looked fine but has not materialised in practice, or that the site actually has very few patients, or that they have some specific problem which is unique. In some cases, the solution will be to extend the recruitment enhancing tools to these sites or, if there are no patients, to close the site down.

CONCLUSION

This approach can be summarised in the following steps:

  • Take care to lay out the issues facing recruitment and retention
  • Map potential solutions against the issues, starting at the most fundamental, usually the protocol, site resourcing and the impact of the trial on patients’ lives
  • Choose solutions on the basis of a risk and cost assessment, recognising that keeping any back for contingency may turn out to be the least effective and more costly approach
  • Run a cascading review with the project team, beginning with issues for the whole trial down to issues per country and then per site, coupled with a review of the agreed targeted sites for specific solutions
  • Follow up with a performance review rapidly – before the recruitment period is a quarter of the way through – to extend solutions to any sites unexpectedly failing to deliver

Whether these services are provided by expert companies, working closely with project teams, or sponsors and CROs undertake the exercises themselves, this as an effective method to ensure that recruitment and retention supporting tools are implemented efficiently, while allowing major sites sufficient scope to deliver actual meaningful speed-ups in trial timelines.


Read full article from PDF >>

Rate this article You must be a member of the site to make a vote.  
Average rating:
0
     

There are no comments in regards to this article.

spacer
Graham Wylie is the CEO of MRN Ltd, a clinical trial support organisation. He started his career at Pfizer in 1989, working as a Clinical Project Manager for a large Phase III programme, and later worked in their New York HQ running an enterprise-wide business process re-engineering programme. He joined Parexel in 1999 as Medical Director for Northern Europe, and was made Vice President of Account Management in 2002. He joined Healthcare at Home in 2005 to create and run their clinical trials division, taking it independent in 2006 with a management buyout.
spacer
Graham Wylie
spacer
spacer
Print this page
Send to a friend
Privacy statement
News and Press Releases

Merck Introduces New Integrated Plug & Play Upstream Development Service

• Adaptive approach to cell line development, analytics and clone selection for emerging biotechs and start-up • Tailored upstream development from a single source reduces time to clinic by 20 percent • Fast-track process reduces timeline by 10 weeks for first pharmacodynamic experiment
More info >>

White Papers

ECCRT

ECCRT

The European Centre for Clinical Research Training (ECCRT) is a professional clinical research training provider focusing on the transfer of implementable knowledge for the day-to-day activities of our participants whether being new to the industry, starters on the job, or seasoned professionals. Our mission is to facilitate Clinical Research professionals to excel in their job for the benefit of patients. We aim to achieve this by providing clinical research professionals with competencies to develop new therapies for patients quicker & more efficiently, without jeopardizing quality and safety.
More info >>

 
Industry Events

Formulation and Drug Delivery Series UK

8-9 July 2020, Oxford Global

This event brings together leading formulation, drug delivery and biologics manufacturing experts from around the world across two days. The panel of prominent industry leaders and world-leading scientists will share the latest case studies, innovative developments for novel therapeutic products and strategies for drug development.
More info >>

 

 

©2000-2011 Samedan Ltd.
Add to favourites

Print this page

Send to a friend
Privacy statement