72 2007 BIO International Convention OFFICIAL PRE-EVENT PLANNER

I n multinational clinical trial planning, selecting countries is the first phase of determining where the study will be conducted. A

reliable method for identifying optimal countries is called “recruitment barrier scoring.” It starts with clinical science but relies on proven marketing techniques to narrow down those countries where recruiting for a given protocol will be most feasible. This method involves understanding a study protocol’s enrollment challenges and then determining through meticulous market research where those challenges will be lesser or greater.

Understanding subject recruitment challenges begins with reading the protocol. Of course, the disease category and inclusion and exclusion criteria indicate which subjects are eligible for potential participation. Understanding the full implications of how a study will be conducted and how subjects may perceive it will affect them also provides additional “soft” data that will be useful in determining how to interpret research.

Keeping that in mind, identify which subject recruitment factors for each country will be most relevant to research and measure for the study. Each receives a negative, positive, or neutral score. Factors such as how prevalent the disease is in a particular country will be relevant to measure for nearly every study. Other factors will depend on the more subtle nuances of each protocol. The following recruitment factors are commonly

investigated:• Prevalence• Protocol-specific factors• Access to care• Attitudes about treatment options• Subject–physician relationships• Competing studies• Site initiation, recruitment rates. Prevalence: This score indicates

how common a condition is in each country. Many sponsors may be already using this particular approach, but it is only an initial step toward pinpointing the right countries and locations within those countries.

Protocol-Specific Factors: Some details of the protocol will become obvious recruitment factors to measure. Exclusion and inclusion criteria may disallow participants who have a particular comorbidity. For example, a type 2 diabetes study that disallows obese subjects may present a significant subject recruitment challenge. Research into the prevalence of that comorbidity will allow you to assign this factor a score to be weighted and considered among the other recruitment barriers.

Access to Care: What type of care does the disease or condition require, and how available is it in each country? Good access to care can be positive or negative, depending on the stipulations of a protocol. Poor access to care can also go either way. For example, if it is necessary that subjects have previously failed two treatment options to qualify, ample access to care will work in the country’s favor (it will receive a higher score) because more

subjects will likely have had access to more treatment and may thus fit the protocol’s failure requirement. On the other hand, in a country with poor access to care, it may be less likely that a high number of subjects have received two previous treatments (Figure 5).

Attitudes About Treatment Options: How subjects feel about existing treatment options for their disease may significantly affect enrollment outcomes. If most people are satisfied with available treatments, the challenge will be greater, and this score will be lower. However, if there is something about the new treatment, such as how it is administered or its potential effects, which may address

The Business

Subject Recruitment Planning for Multinational Studiesby Karen K. Rumrill (adapted by George Miller)

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Clinical Research/Clinical Trials

74 2007 BIO International Convention OFFICIAL PRE-EVENT PLANNER

some patient concerns, this score could rise. Although existing research may help you determine subject attitudes, finding these answers may require subject focus groups.

Subject–Physician Relationships: How subjects view doctors, and how

they relate to their physicians, varies from culture to culture. Do subjects revere those in the medical profession and believe they have an elevated status? Although such reverence may lead to easier enrollment, it can be a barrier to a timely informed-consent

process and could influence subject responses in subject-reported outcomes.

Competing Studies: Studies occurring at the same time will compete for subjects, especially when they are in the same disease category. You should also research studies in other categories that could draw a subset of your study population. With a rheumatoid arthritis study, for example, you would consider how many other rheumatoid arthritis trials are going on in each country and also consider studies in other therapeutic areas that are testing treatments on subjects who have rheumatoid arthritis. It is also significant to evaluate the volume of studies that sites in each country are handling because overworked site professionals can affect a study’s recruitment potential.

Site Initiation and Recruitment Rates: A number of “administrative” factors can affect a country’s ability to initiate sites and recruit subjects. These may include technological infrastructure for processing data or

Figure 5: Countries are scored according to specific recruitment barriers. In this example, prevalence of hypothetical disease is measured. (BBK WORLDWIDE)

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absorption transport or diffusion of a drug from the site of administration to the bloodstream

adverse effect/event any dangerous side effect of a drug

carcinogenicity the ability of a substance to cause cancer

CGMP current good manufacturing practice

clinical trial protocol a document that describes the objective(s), design, methodology, statistical considerations, and organization of a clinical trial; may also give the background and rationale for the trial, which are otherwise provided in other referenced documents (e.g., an investigator’s brochure)

distribution the dispersal of a substance throughout an organism’s body

efficacy proven ability of a drug or vaccine to produce a desired clinical effect at the optimal dosage

excretion the elimination of waste material by an organism

genotoxicity measure of chromosomal damage caused by a given substance

immunogenicity tendency to elicit an immune response, which can at least lead to destruction of a product before it can do its job and at worse lead to death of a patient through, e.g., anaphylactic shock

institutional review board (IRB) a committee of physicians, statisticians, researchers, community advocates, and others that ensures the ethics of a clinical trial and that the rights of study participants are protected

investigator the person (scientist or doctor) in charge of a research study; if there are two or more, then one person may be designated the principal investigator (PI)

metabolism the build-up, break-down, and use of chemical substances by an organism

mutual recognition procedure acceptance by one country of another country’s certification that satisfactory standards have been met (especially between countries of the European Union)

placebo an apparently indistinguishable drug product without the active substance (or vaccine that will elicit different immune response from the one being tested) administered to some clinical trial subjects, who serve as a control group

qualified person an official who is responsible for certifying the suitability for release of medicinal products (requires specialized training and experience)

recall mandate that a batch or an entire production run of a drug be returned to the manufacturer (usually due to the discovery of safety issues)

reproductive toxicology studying the effects of chemicals on adult reproductive and neuroendocrine systems as well as embryo, fetus, neonate and prepubertal mammals

side effect any effect of a drug that is not its main or intended effect (may be of no concern, can be bothersome or even dangerous)

sponsor a company or other organization that takes responsibility for the development of a product

TERMINOLOGY OF CLINICAL TRIALS

how slowly or how quickly ethics committees review study materials. Combine all related research data into one recruitment rate score.

WEIGHTING

Each factor you have researched will vary in its relevance to or affect on the protocol’s enrollment potential. Allow for that variation by assigning each factor a “weight,” or percentage of relevance. For example, competing studies may be a major concern for a protocol involving a rare disease and thus be given a higher weight. Prevalence, on the other hand, may be low for all countries and remain a neutral factor.

After weighting, compare scores for each factor to identify those countries with the fewest and the most recruitment barriers.

Karen K. Rumrill is leader of operations at BBK Worldwide, kkrumrill@bbkworldwide. com; www.bbkworldwide.com. This article first appeared in BioExecutive International’s November 2006 issue on pages 40–43.