Twenty years ago, research sites alone would provide their total enrollment quota simply by reaching into their own database of patients. But in the last two decades, the clinical trial landscape has changed and the ripple effect has meant that sites need to go outside their practice for patients.
Increases in clinical studies and protocol complexity are putting a strain on sites and their ability to recruit solely within their own walls. Competition for the patients has increased, while fewer patients in a practice are qualifying for contracted studies. Today, sponsors are responding to this challenge by routinely using additive recruitment services to provide 30-50% of randomized subjects. Additive patient recruitment is defined as the process of sourcing patients who are not indigenous to a site’s practice, via the services of a third party provider.
These additive patients optimize site enrollment performance and help ensure that a sponsor’s investment in sites produces the required number of patients in the prescribed timeframe, even when sites have run out of their own patients. Therefore, additive patient recruitment is no longer a nice to have or a rescue solution — it is very often a critical part of the study plan.
For some sponsors, however, the temptation to forgo additive patient recruitment in favor of what appear to be safer or more cost-effective options is still prevalent. These traditional options have significant shortcomings in the new world order of clinical trial complexity and competition.
Once a study team agrees that sites alone will not meet their enrollment in time, there are generally a limited number of choices available to fill the patient gap. These options all have budgetary implications, and it is critical to analyze the financial and value impact of each. The analysis should answer the question: “What is the most cost effective manner to obtain the patients we need, within the timeframe we need, and at the lowest risk of failure?”
Successful evaluation requires a clinical study team to compare the current cost of obtaining patients through additive recruitment versus the cost to continue trying to add more patients via the same site-based approaches.
To benchmark the latter scenario, let us consider for the purposes of illustration that a sponsor needs 300 patients for a phase III study. The study team concludes that 50 sites will be required to enroll the 300 total patients (six patients per site). Once we know the average number of patients per site, cost per patient can be calculated.
For some sponsors, however, the temptation to forgo additive patient recruitment in favor ofwhat appear to be safer or more cost-effective options is still prevalent.
The process of vetting, hiring, maintaining and winding down sites requires time and cost, driven by activities such as:
- Site identification
- Site negotiation and contracting
- Training site staff on the study design, data capture systems, filing requirements, etc. (may include investigator meeting attendance costs)
- Supplying site with study related materials, drug supply, and equipment
- Performing a site initiation visit
- Site monitoring
These items reflect sunk costs incurred whether the site ever enrolls one, three, or the desired six patients. Numerous clinical trial costing tools such as ClearTrial and a wide variety of publicly available research estimates that total sunk costs range from $20,000- $75,000 per site. Such a range largely reflects the costs of training the site depending on study complexity, the costs of supplying the site depending on study procedures, and whether or not the sponsor is performing the work themselves or outsourcing to a CRO.
Going back to our example, we will assume a site cost average of $30,000 and estimate that each site will contribute an average of five patients. Divide those two numbers and the average cost per patient is $6,000 (and the study team will still be 50 patients short of the enrollment goal).
Through this simple analysis, we have successfully benchmarked the current cost for each internally “recruited” patient. Now the study team is prepared to evaluate options to compensate for the enrollment shortfall.
Limited options for fixing enrollment issues The most common options study teams consider are:
Add more sites
Do nothing and wait
Give sites money for local advertising
Hire a patient recruitment company
Let us examine each of these options and assess their typical impact on time, budget and enrollment effectiveness.
Add more sites
When the top sites fall short on their numbers, there is little chance that adding second or third tier sites will match or do better than those sites with higher expectations or more robust patient populations. Moreover, it takes months and the aforementioned expense ($20,000 to $75,000) for the study team or CRO to locate, evaluate and initiate more sites.
Existing sites are ready to process patients right now – but do not have enough qualified candidates within their ranks. When sites have run of their own patients, they are akin to empty processing facilities, waiting to receive the raw materials needed to produce enrolled patients. Study teams, under pressure, simply do not have the time to source and initiate new sites, but could easily increase the production capacity of existing ones through additive recruitment – providing existing sites with new influx of patients to raise their enrollment contributions.
Waiting to see if sites can fix the problem
Sites are small businesses – sponsors have hired them to provide the study with patients, for which sites are paid per a negotiated contract. This is revenue sites need to pay their own expenses and realize a profit, so they are not holding back when it comes to enrolling patients. If they are not able to source patients now, they are not likely to suddenly discover patients in a few weeks. And as the study team waits for patients to magically to appear, the budget continues to be spent – sites still need to be monitored, IVRS is still running, drug supply is expiring, etc. Doing nothing has a substantial cost.
Provide money for local advertising
Some sites do a good job spending their advertising stipends efficiently, but many do not, and will be the first to admit it. Moreover, there is limited or no tracking of how the sites spend these dollars and what resulted from the effort. How do study teams know that all the money allocated was specifically spent on their study, versus used on a competitive study? Do they know how many enrolled/randomized patients they received for the stipend?
Generally speaking, most study teams would not accept such a lack of accountability in any other area of study management or organization. Individual study sites are not experts in advertising or media buying. They are experts in patient care. Providing $2,500- $5,000 to each site for local advertising is a long-standing practice, if not tradition. Yet, with ineffective patient recruitment still a pervasive issue, the efficacy of providing local advertising stipends to sites remains in question.
The increasingly popular option
Hiring a specialty vendor to design and manage an additive recruitment campaign, focused on enhancing individual site enrollment, is the option that is increasingly making sense from a time, risk, and financial standpoint. However, the call to action is not to simply hire a company that specializes in patient recruitment advertising. Patient recruitment is not advertising. Advertising is advertising. True patient recruitment is a set of proven processes that manage recruitment from the moment a patient responds to an advertisement through their initial eligibility pre-screening, first visit to the site, review of consent, and ultimate enrollment in the study. This is central management designed to optimize the enrollment performance of every site. These processes use the raw material created by many different forms of advertising to ensure that, with the help of each site, potential patients are managed and enrolled in the most timely and cost-efficient manner. A central recruitment campaign should ensure participating sites always have a steady, well-paced supply of additive, suitable patients to screen — patients these sites would not have otherwise enrolled in the study because they are not part of the sites’ existing databases.
In other words, the recruitment effort must provide high quality raw material for clinical research processing centers (sites) to be running at peak efficiency until the patient quota is met. So the question is: How do clinical study teams select the recruitment partner who can consistently and reliably produce results?
Selecting a recruitment partner…choose wisely
The primary mission of a patient recruitment partner is to design and implement a plan that provides a discrete number of patients to fill the gap sites cannot fill on their own. That is the basic premise and function of this unique business we know as patient recruitment. The primary mission of the patient recruitment partner is not to develop great advertising campaigns. The capability to create effective patient recruitment advertising is a given, not a differentiator. Therefore, the fundamental selection criteria for the study team is to find a partner that can — in contractual not anecdotal terms — contribute a predictable number of additive patients over a specific period of time.
That partner should also be able to offer a fee structure based on the delivery of enrolled/randomized patients depending on the therapeutic area, and that per-patient fee can often include all the set up, project management, and pass through fees. In other words, a partner confident in its assessment of the enrollment challenge will contractually put the vast majority of its fees on the delivery of patients into the study.
Clearly those patients should not be ones the sponsor would have otherwise received from the sites’ own activities. This also requires a symbiotic relationship where the selected recruitment partner has access to independent, blinded controls (e.g., IVRS-data matching) to verify which patients enrolled in the study as a result of their work.
Budget accordingly…and confidently
It is not unusual for there to be a 50 to 1 ratio of people who respond to a specific study advertisement for every one patient who enrolls/randomizes.
If it costs $60 to generate a respondent, then that hypothetical recruitment campaign would cost the sponsor $3,000 per randomized subject, not including any program fees (e.g., project management, call center, site support fees). For the uninitiated, $3,000 may appear expensive. However, as presented earlier in the benchmarking exercise, it is not unusual for a sponsor to already be technically paying $5,000, $10,000, even $20,000 per patient (for the hardest studies) based upon the average number of patients enrolled per site and the total cost of hiring the site.
If an additive recruitment campaign results in a sponsor avoiding a three-month enrollment delay and/or prevents it from adding 10 second- or third-tier sites at an average cost of $30,000 per site, there is a high likelihood that the campaign will either be cost neutral or cost positive. And, importantly, the study will enroll on time.
Looked at another way, additive patient recruitment does not mean additive budget, especially when selecting a partner with a results-based philosophy and contracting approach. Sponsors should not be afraid to ask for both. Study teams should also not be surprised when the CRO, despite having its own patient recruitment department, will hedge on offering this type of results-based contract. Expedited enrollment, in fact, reduces the overall earning capacity of CRO projects which are driven by time, materials, and the number of participating sites. The more sites and time involved, the more a CRO makes, especially on change orders when enrollment stalls.
Proactively budgeting for additive patient recruitment services is, with the help of the right partner, a fairly straight-forward exercise that is appropriately vetted through the sourcing and procurement departments of most sponsors. Study teams should ask their outsourcing representatives to source multiple proposals and look for the company that offers detail on the process, and not just the advertising. Moreover, they should look for the company that puts its own funding at a payment milestone that is truly meaningful and truly results based, like enrolled or randomized patients.
With the right partner, patient recruitment is a predictable, repeatable process that optimizes site performance and prevents budget overruns caused by adding sites, adding time, and paying for CRO change orders.
Courtesy 2011 Acurian, Inc. White Papers