Chances are that you have clicked on this link because you may be interested in participating or learning more about clinical trials – also known as clinical research. We hope that the information assembled will provide you with a good understanding about clinical trials and what it might mean for you.

Clinical Research doesn’t really start with a clinical trial; its foundation has been laid long before.

Basic Research: Like all research, it starts somewhere in someone’s mind, usually a scientist. People who think and observe without pre-formed judgments are at the center of all renewal. The observations are linked by thought and sometimes, after long and arduous work, lead to new ideas and inventions like the discovery of atorvastatin (a molecule that blocks the synthesis of cholesterol in the liver, thus lowering blood cholesterol).  As high blood cholesterol is a common problem for many people because it increases the risk of cardiovascular disease, the discovery of this molecule by a chemist working for Parke-Davis, Ann Arbor, Michigan in 1985 meant a great advance for millions of people.

Atorvastatin, marketed by Pfizer as a calcium salt under the trade name Lipitor.

Just recently, on November 30, 2011, this amazing drug came off patent, which means that there is now a generic atorvastatin on the market.

Once a basic observation is described, like the HMG-CoA pathway in the liver that is responsible for the synthesis of cholesterol, hundreds of experiments are run and rerun to obtain in-depth understanding of the initial observation/s. This basic research is done in institutions that you might have heard of, e.g. National Institutes of Health (NIH), National Cancer Institute, MD Anderson Cancer Center, The Salk Institute of Biological Sciences, The Scripps Research Institute, Pharmaceutical and Biotechnology companies and Universities around the globe.

Pre-clinical Research: Once basic research has found sufficient evidence to demonstrate the mechanisms that cause a disease, such as in the atorvastatin example, the search for a new treatment can be initiated. Presently, many treatments are targeting very specific molecules to either ‘block’ or ‘inhibit’ their activation, or on the contrary to enhance or increase their activity. Other treatments may help replace important substances in your body like the replacement of thyroid hormone for patients who suffer from hypothyroidism; or they may help deliver drugs to the right place where they should be active, avoiding unnecessary exposure to the entire body.

The research of these new treatments continues to be done in laboratories, test tubes, and eventually in animal models.  Before any new drug can be given to a human being in a clinical trial, it has to undergo extensive testing of all aspects of potential toxicity (e.g. cardiac toxicity, cellular toxicity, resistance development, hypersensitivity).  These tests are mandatory by the Food and Drug Administration (FDA). The efficacy aspect of a new molecule will also be studied in cell cultures or animal models (e.g. the activity of antibiotics is tested in culture against bacteria). These in-vitro and in-vivo tests allow the scientists and doctors to make a reasonable, data-driven assessment on how the drug will work in the human body and what the potential benefits and risks are.

Another example of an important new treatment that was developed in the past decade is Herceptin, a (monoclonal antibody) drug that blocks the activation of a transmembrane protein called Her2.  To view a video on Herceptin, click here.

Clinical Research: So once a clinical trial begin, years of work, even decades of time, have been invested to develop a new medication (aka ‘investigational agent’,  or ‘compound’). The new medication that you might receive to treat your disease has been studied in many different experiments to understand the behavior of the compound under different conditions and in different settings.

At this point the FDA and the Ministries of Health (MoH) will decide if it is sufficiently safe and beneficial to test the new compound in humans. While there might be differences between the practices in different countries, most follow similar guidelines and regulations in assessing the worthiness of a new drug or device. These guidelines are called the ICH-GCP guidelines that stand for International Conference on Harmonisation of Technical Requirements – Good Clinical Practice. View the guidelines here.

One critical consideration is the assessment of your (the patient’s) potential benefits compared to the potential risk factors that have to weigh in favor of the benefits. If the FDA allows, an Investigational New Drug Application (INDA) to move forward, Clinical Development of this new product can finally begin.

What are Clinical Trials?
A clinical trial is a research study that evaluates the performance of a medical product (medication, therapy, medical device, diagnostic test, etc.) in normal volunteers (people that are healthy) or patients (people with a medical condition or disease).

In a clinical trial, health care practitioners (e.g., doctors, nurses, etc.) use a specific set of procedures that are based on science (i.e., protocol) to evaluate the medical product.  For example, you may be given a new drug to treat diabetes and the doctor may then interview you, and perform diagnostic tests to determine if the drug controls your blood sugar as it is supposed to.

Clinical Development is structured in three research phases that occur sequentially but depending on the circumstances may also occur in parallel. There is also a fourth phase that applies to drugs that have already received market approval.

Four Phases of Clinical Research

Types of Clinical Trials
The type of clinical trial will vary depending on:

• The type of medical product (medication, therapy, medical device, diagnostic test, etc.)
• The stage of product development (e.g., product that is already marketed, new product, etc.)
• Trial sponsor (e.g., government, private company, university, etc.)
• Some clinical trials are in normal volunteers (people that are healthy) and some are in patients (people with a medical condition or disease)

Clinical Trials for Medical Devices
In contrast to the development of a new medication, the clinical trials used to develop a new medical device or diagnostic test are generally of shorter duration and include fewer patients.  However, the precautions and monitoring to protect patient safety and the care that you receive, is the same.

Overview of a Typical Clinical Trial
First, the clinical trial is reviewed and approved by an independent Institutional Review Board (IRB) or Ethics Committee (EC).  The IRB/EC is a group of people, who make sure that the clinical trial, and the health care practitioners, who conduct the clinical trial, protect patient rights and safety at all times during the study.

Second, a doctor or nurse explains the study to you.  It is important that you understand the risks, benefits, and your rights as a subject in the trial.  If you agree to participate in the clinical trial, you sign an “informed consent form,” which indicates that you agree to participate in the study.

Important – Steps one and two are designed to protect people who participate in clinical trials.  One should never participate in a clinical trial if you do not understand the risks and benefits of the medical product and your rights as a participant.

Third, you participate in the clinical trial, which usually consists of the following:

• Sign the informed consent form before any trial procedures are performed
• Screening procedures to make sure that you are eligible for the study and to establish a baseline
• Use the medical product (e.g., take a medication, be treated by a medical device, undergo a diagnostic test, etc.).  This could range from a 1-2 minute diagnostic test or you could receive a new medication for months to years depending on the type of clinical trial.
• The healthcare practitioners monitor and measure your response to the medical product (e.g., they measure your blood pressure to see if the antihypertensive drug lowered your blood pressure).
• After you stop using the medical product, a follow-up visit is performed to make sure that you are not experiencing any side effects after receiving the medical product.

Comparing Typical Medical Care to Clinical Trials

(More)

Wednesday, July 18,2012

CARLSBAD, CA – July 18, 2012. Patient Recruiters International, Inc. (PRI), a leading provider of direct patient access solutions for patient recruitment and retention services, announced today the launch of ClinicalStudy.org for hosting clinical trial websites and landing pages for the registration of interested research subjects.

ClinicalStudy.org offers customizable clinical study web pages via sub-domains for research sponsors. For example, a study in diabetes might have the subdomain “diabetes.clinicalstudy.org”. The site enables rapid online prescreening and patient engagement with high organic search engine placement. In addition, patients may register for future clinical studies on the site.
As posted on PRI’s site: www.patientrecruiters.com
“We are pleased to make ClinicalStudy.org available to the clinical research community. Dedicated domains are an expensive process to design and develop, especially when only used during the active patient enrollment period,” states Larry Risen, President of Patient Recruiters International. “With ClinicalStudy.org, we are offering a far more cost-effective solution for clinical study websites that includes all the capabilities sought after by research sponsors.”

About Patient Recruiters International, Inc. (PRI)
Patient Recruiters International (PRI) is a global patient recruitment services organization that combines powerful new technologies with time-tested methods to achieve the recruitment objectives of research studies. PRI’s targeted methods of using patient databases and online communities enables it to quickly enroll the right subjects for research studies. As part of this reach, PRI operates ClinicalStudy.org, customized social media initiatives, and risk-shared contracting models. As a full-service patient recruitment services organization, PRI also provides high touch patient retention services and operates under a Good Clinical Practice (GCP) program.

For more information about PRI, please visit www.patientrecruiters.com.

Contact:
Katy Hysong
(760) 448-4826
khysong@patientrecruiters.com

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December 19, 2008 ~ Market researchers commonly use a mathematical technique called intent scale translations to convert a respondent’s stated purchase intentions into actual purchase probabilities. Intent scale translations provide the researcher with an estimate of actual buying behavior and accounts for over estimation on the part of respondents’ participation in the research. Companies can then rely on purchase intentions to forecast the purchase of new products or repeat purchase of existing products. In other words, if a customer states that he/she prefers a particular product over another, what is the probability that he will actually follow through with making the purchase of the preferred product?

Studies have shown that consumer’s self-reported intentions to purchase do not reliably predict their purchasing behavior (1). Market researchers needed to develop a method to more accurately translate a respondent’s response to survey questions into actual probabilities that they would buy or use a product of interest. Intent scale translations take data from a customer survey on purchase intentions and convert the data into a prediction of purchase probability by using comparisons of stated vs. actual purchase behavior.

Traditional intention rating scales use a 5-point scale to show consumer’s intentions of buying a product. In this traditional method, people who scored a rating of 1 or 2 were typically assigned a 0% chance of buying the product. The research of Thomas Juster (2)found that the 5-point scale was an inaccurate way of measuring buyer intention and that a buyer with a score of 1 and 2 actually had a greater than 0% chance of buying the product. Juster created his own buyer intention scale that would improve a marketer’s ability to forecast behavior from intentions and account for changes in a consumer’s true intentions between the time surveyed and the time of actual purchase. Juster developed an intention scale that adjusted the intention scores by analyzing the actual future purchase behavior of consumers after being surveyed. He developed a new 11-point scale which implied simple methods for calculating intentions. It stated that if a sample group was asked if they would buy a new car in the next month and they were to choose a number correlating to the likelihood on a scale of 0 to 10, 10 being the greatest possibility, and the average score came out to be 2.5 out of 10 then that would translate to 25% of the general population purchasing a new car in the next year. The research described here will provide a demonstration of how purchase intention scales are used to predict actual consumer purchase behavior.

The traditional 5-point scale is used to give a general estimate on consumer’s purchase intentions of something. It can be used to predict everything from consumer’s intention on buying a certain product to predicting where people may travel for vacation or even the likelihood of a doctor ordering a particular diagnostic test for a patient. The 5 point scale is routinely used across many types of businesses and industries. Below is a typical scale and description of a 5 point Intention Scale.

Table 1. Example of 5-Point Intention Scale

The 5-point scale, also referred to as the Likert scale, is still commonly used by major corporations to understand consumer’s product purchasing intentions or simply conducting basic surveys. It is especially useful in telephone surveys and mall research where consumers are taking a verbal survey and their responses are being recorded by the researcher.

One major corporation that still uses this 5-point scale is AC Nielsen, a marketing research company that conducts surveys on a variety of consumer products. AC Nielsen provides a service called BASES to present pre-market insights to consumer goods companies. Consumer good manufacturers often use outside market researchers for conducting unbiased surveys. BASES has become the industry standard forecasting model. Table 2 demonstrates how a 5-point scale is translated into purchase probability. Note that Intent Probability overestimates predicted probability when comparing to the AC Nielsen BASES translation scale (3). AC Nielsen and others have conducted diary studies where consumers record their actions for the researcher over time and follow-up market research to measure actual observed purchase behavior compared to stated intentions. This has resulted in establishing a correction factor that adjusts the intent probabilities of purchase.

Table 2 Use of 5-Point Intention Scale in Translating Purchase Probability

As previously mentioned, another common purchase intention scale used is the 11-point scale, created by Thomas Juster, which he found to be much more accurate than the 5-point scale. On the Juster scale, every description correlates directly to a number ranking of 0 to 10. The reason for this alternative scale is to give higher values to people ranking lower scores. In the 5-point scale, someone who receives a score of 1or 2 were sometimes assigned a 0% chance of using the product. Juster found this to be incorrect and set out to fix it by coming up with his own scale. In the 11-point scale in Table 3, the score relates directly to the probability of use. For example, someone with a score of 4 is found to have a 40% chance of using the product.

Table 3. Juster’s 11-Point Probability Scale

Herein we report a review of consumer studies as it relates to a Translated Probability Intent Scale. What I found was a research study on Fast-Moving Consumer Goods. This particular study observed three popular types of soups and four types of yogurt. It involved a face-to-face survey performed by the Palmerston North Household Omnibus survey (4). The consumers were asked about their purchase intent of each of the items and an overall percentage of purchase probability was obtained. Then the respondents were re-interviewed by telephone a month after the original survey and estimates of actual purchase intent were obtained. For example, Fresh and Fruity yogurt had a predicted purchase rate of 36.2%, but when the respondents were re-contacted, only 22.6% had actually purchased the Fresh & Fruity yogurt. This indicates an overestimation of expected purchase intent by13.6%. Table 4 shows the results from this survey for various products.

Table 4. Purchase Intention Using Juster’s 11-point Scale

We plotted all of the actual and predicted probabilities on a scatter plot with Predicted Purchase Intent on the X-axis and Actual Purchase Behavior on the Y-axis. In Figure 1 the graph and equations generated from the 11-point Juster scale results are shown.

Figure 1. Juster 11-Point Scale: Predicted vs. Actual

Each mark represents a unique study. A “best fit” regression line was applied to the resulting plot using the best fit line feature in Excel and the equation of the line was calculated. The regression line shows y = 0.8845x – 0.0481. The linear correlation coefficient, r, gave a strong correlation coefficient of r = 0.9713. A perfect correlation is + 1 where all points lie on a straight line. A correlation coefficient greater than 0.8 is considered strong (Marino 149). The coefficient of determination, R2, was calculated and found to be R2 = 0.9435.

We took the Juster Scale Intent Probability numbers in Table 3 and entered into them into the regression equation, y = 0.8845x – 0.0481 (x= 0.99, 0.9, 0.8, etc). These represent the predicted purchase probabilities “x” in the equation. The decimals are then converted back into percentages for the final Translated Probability Table 5 below:

Table 5. Just Scale Translated Probabilities

From this analysis 83% of actual intended buyers (those with a scale score = 10 described as certain purchasers) can be expected to buy the product vs. number predicted. Of those with a score of 9 and intent probability of 90%, only 75% would actually be predicted to purchase the product. Of those with a score of 5 and intent probability of 50%, only 39% would actually be predicted to purchase the product. This demonstrates how statistics can be used in intention scale translations to better predict a consumer’s actual purchase intent from survey data. Statistics like this are used by market researchers to help guide marketing, advertising and sales forecasts for product manufacturers.

To download a PDF version, click here.

Bibliography

1. Sheppard, Blair H., Jon Hartwick, and Paul R. Warshaw. “The Theory of Reasoned Action: A Meta-analysis of Past Research with Recommendations for Modifications and Future Research.” Journal of Consumer Research 15.3 (1988); 325-343.

2. Juster, F. Thomas. “Consumer Buying Intentions and Purchase Probability: An Experiment in Survey Design.” Journal of the American Statistical Association 61 (1966); 658-696.

3. Chandon, Pierre, Vicki G. Morwitz, and Werner J. Reinartz. “Do Intentions Really Predict Behavior? Self-Generated Validity Effects in Survey Research.” Journal of Marketing 69 (2005); 1-14.

4. Brennan, Mike, and Don Esslemont “The Accuracy of the Juster Scale for Predicting Purchase Rates of Branded, Fast-Moving Consumer Goods.” Marketing Bulletin 5 (1994) : 47-52

5. Marino, Kenneth E., Forecasting Sales and Planning Profits. Chicago: Probus Publishing, 1986.

6. The Nielsen Company. Marketing Intelligence. 13 Dec. 2008 <http://www2.acnielsen.com/site/index.shtml>.

CARLSBAD, CA – Nov. 10, 2011 – Patient Recruiters International, Inc. (PRI), a full-service patient recruitment organization announced today the launch of its online patient community, GoHealthPanel.com. This online community is a general population site of people wanting to become involved in the research, education and contribution of different health conditions and solutions in today’s research market.

“Finding subjects for research studies such as clinical trials is known to be a lengthy and expensive process for sponsors,” states Larry Risen, President of PRI. “With GoHealthPanel.com we are able to address key recruitment challenges by providing a direct-to-patient access solution and a vehicle to pre-screen subjects online. It’s a highly efficient process.”

Through GoHealthPanel.com, members will be able to access information on health-related research opportunities, learn about current treatment trends for their condition and share their unique insights and experiences. The overall community experience offers members many benefits such as receiving incentives for research participation, accessing new treatment options, and contributing to the greater good of research.

“With engaged research subjects being so critical to reliable and timely research, we are excited to launch this online community for delivering pre-qualified candidates to sponsored research,” says Risen.

Through extensive health history information and unique recruitment strategies, GHP is constantly targeting the right panelists with the right intentions, solving the challenge of delivering quality research panelists for studies. This approach yields higher numbers of potential research subjects and ultimately, more reliable and predictable outcomes from the research participants.

About GoHealthPanel.com

GoHealthPanel.com can fulfill the enrollment and participation requirements for clinical trials, observational research, and market research studies. GoHealthPanel.com offers researchers the ability to connect with the right patients. For more information on GoHealthPanel.com, please visit www.gohealthpanel.com

About Patient Recruiters International, Inc. (PRI)

Patient Recruiters International (PRI) is an innovative patient recruitment services organization that combines powerful new direct patient access strategies with time-tested methods to achieve the recruitment objectives of research studies. PRI’s method of using patient databases and online communities enables it to quickly target the right subjects for research studies. PRI has built confidence and reliability with its innovative tools including targeted direct patient access, online patient communities, customized social media initiatives, and risk-shared contracting models. For more information about PRI, please visit www.patientrecruiters.com.

CARLSBAD, CA – Nov. 1, 2011 – BioTrak Research Inc., a specialty contract research organization announced today the launch of a wholly owned affiliate, Patient Recruiters International, Inc. (PRI), a full-service patient recruitment organization.

The launch of PRI is a direct response to the increasing demand for qualified research subjects in the clinical research field. With patient recruitment and retention as a critical part of successful clinical research, PRI accelerates the recruitment and enrollment process and reduces per-patient recruitment costs for Sponsors through new and powerful direct-to-patient access solutions.

“We see the need for more creative and targeted patient recruitment strategies as the competition for research subjects continues to grow,” states Larry Risen, President of Patient Recruiters International. “PRI addresses this challenge by using large proprietary patient databases, online patient communities and social media to increase referrals for research studies.”

As a full-service patient recruitment services organization, PRI provides patient retention services as well as innovative recruitment solutions that combines direct patient access strategies with traditional media such as television, video, radio, and print advertising. PRI’s specialized data capabilities can reach over 120 million covered lives in the U.S. As part of this reach, PRI is launching GoHealthPanel.com, an online community of people with health conditions wanting to become involved in meaningful research.

“We understand the clinical research process” states Karl Cremer, PharmD, Senior Vice President, Clinical Affairs. “When the protocol is finalized, the patient population always seems to be smaller than when you started. PRI has the experience, strategies, and tools to find the right patients in an accelerated fashion.”

Previously operating as a unit of BioTrak, PRI has a 12-year history of recruiting subjects for over 300 research studies involving patients, pharmacists, and healthcare professionals.

About Patient Recruiters International, Inc. (PRI)
Patient Recruiters International (PRI) is an innovative patient recruitment services organization that combines powerful new direct patient access strategies with time-tested methods to achieve the recruitment objectives of research studies. PRI’s method of using patient databases and online communities enables it to quickly target the right subjects for research studies. PRI has built confidence and reliability with its innovative tools including targeted direct patient access, online patient communities, customized social media initiatives, and risk-shared contracting models. For more information about PRI, please visit www.patientrecruiters.com.

For more information contact:

Cynthia Davis
Patient Recruiters International, Inc.
cdavis@patientrecruiters.com
760-448-4834

Prepare for REMS Assessments and Increase Risk Awareness among Interval and External Stakeholders

Please join Larry Risen, President of BioTrak Research on April 28, 2011 at 9:00AM. Larry Risen will be speaking at the conference on a “New Data Analysis Tools for Assessing the Performance of REMS.”

For more information, please click here.

Abstract

The adequacy of labeling for instructions, cautions, and contraindications becomes pivotal in the benefit/risk assessment of medical products. Our research using observational study designs in mock product use trials has predicted medication use error rates in the range of 40-70% for drug device combination products. Early testing of proposed labeling can identify problem areas in label comprehension that leads to a potential medication or administration error or user frustration resulting in medication non-compliance. A well designed labeling comprehension study is not an expensive proposition; most studies can be performed with a small sample size (n < 100) for baseline observations and testing of label revision(s). In our experience, such studies support labeling changes that can significantly reduce potential product misuse and medication error to acceptable rates.

1. Introduction

Initiatives to reduce health care spending have ultimately resulted in many medical procedures increasingly being moved to the outpatient environment and/or home care setting. As such, patients, family members and/or other non-medically trained personnel are performing therapeutic and diagnostic procedures such as drug administration using alternative drug delivery devices, inhaled therapies, glucose tests, etc. Adequacy of the labeling instructions, cautions, and contraindications and the use of supplemental instructional labeling have become pivotal in the benefit-to-risk assessment of these treatments or tests. This paper describes a research methodology offered by BioTrak Market Intelligence, Inc. (BioTrak) for evaluating the effectiveness of combination drug/device product labeling prior to product registration as an aid in the development of appropriate labeling and during the post-approval period to assess comprehension and compliance among patients, dispensing pharmacists and patient care providers.

The medication errors staff in the FDA Office of Post-Marketing Drug Risk Assessment (OPDRA) search the FDA Adverse Event Reporting System (AERS) database for all cases of medication error. In a report published in 2001 (Drug Topics October 2001, p 23-24), labeling was identified as one of the leading causes (20%) of medication error along with misinterpretation of the order (10%) and written communication (8%). Additionally, human factors are the leading cause (42%) of comprehension and performance deficit. These data illustrate the importance and need for clear use labeling.

2. Regulatory Context

The FDA has promulgated detailed regulations specifying the form, content and wording of labeling for items such as the identity, dosing, supporting studies, warnings, adverse reactions, contraindications with respect to established drugs and biologics dispensed by a pharmacy or sold over-the-counter (OTC). (Title 21 Subchapter C-Drugs: General Part 201 Labeling). Likewise the labeling requirements for medical devices are specified in Part 801 Labeling. The FDA has required sponsors to thoroughly investigate the adequacy of labeling for OTC switches of prescribed medications. For example, FDA and consumer groups required sponsors to conduct five labeling comprehension studies and five actual use studies before the approval of Prilosec® for OTC marketing. FDA plans to conduct labeling comprehension studies of their own prior to issuing new regulations for covering the wording of statements that request patients to report adverse events. Among the reasons cited for testing these statements were: (1) to determine the best and most precise wording for the statements, (2) to evaluate consumer comprehension of the proposed statements, and (3) to address concerns that consumers who read the statement will mistakenly call FDA in search of medical advice (Federal Register / Vol. 72, No. 22 / Friday, February 2, 2007 / Notices).

For combination products sponsors are expected to submit adequately well controlled scientific evidence for the safety and effectiveness of their labeling. However, to date the FDA has not issued guidance for combination product labeling comprehension studies.

3. Strategies for Labeling Studies

In today’s climate of increasing regulatory control, authorities are demanding more controlled studies to evaluate and verify product safety and the accuracy of product use instructions by all product stakeholders involved in the prescribing, dispensing and administration of the product. Common methods used to evaluate labeling comprehension (prescribing, dispensing and use instructions) typically include one or a combination of the following:

Product Use Simulation Studies – Proposed labeling is drafted and applied to test articles for hands-on evaluation by target stakeholders required to take specific action(s) demonstrating proper administration of the proposed product (drug, device or drug/device combination product).

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Ailment Panel Survey Research – Patients (or patient caregivers) who are potential users of the proposed drug, device or drug/device combination product are surveyed (online, paper-based MD office exit interviews, etc) regarding their interpretation of specific use instructions using both objective and subjective queries.

Patient Registries and Post-Market Surveillance Studies – Once the approved drug, device or drug/device combination product is commercialized, sponsors are frequently required to monitor compliance for a period of time (1 to 3 years is common) to generate patient experiential data. Depending on the risk level of a labeling compliance error, post-market surveillance studies can either be mandatory for all product dispensed (high risk for severe AE), or, in the case of a relatively low risk potential, the post-marketing surveillance can be self-reported by the patient or caregiver on a voluntary participation basis.

4. Case Studies of Labeling Comprehension Trials

Studies of labeling comprehension, compliance and product usability have revealed surprisingly poor product safety and performance results by patients, caregivers, and pharmacists. Figure 1 below is an example of a caregiver study involving manipulations with a novel drug delivery device. One device represented the currently marketed product; the other four devices tested were replacement prototypes. The study revealed labeling as a major source of end user confusion.

Several case study examples follow which we have found indicative of user performance with initial labeling and new product designs. Each example involves a drug with novel delivery device for administration by a patient or caregiver.

Case 1: Pharmacist Study of Dispensing Error with an Adjustable Drug Delivery Device

A pharmaceutical company had developed an adjustable dosage delivery device for an approved medication to treat an acute disorder. The adjustable device was developed to reduce the range of inventory SKUs while offering more available dosing increments. Prior to use, the device required pharmacy setting and locking of the patient specific dose. The device was made available as a pack of two set at an arbitrary default dosage; pharmacists were to set the device at each prescribed dose and lock it. Labeling consisted of an outer box label and insert providing a diagram accompanied by a step by step written procedure. The principle failure modes were identified as 1) failure to set the correct dose resulting in incorrect dosing and 2) failure to lock the device thereby disabling its use.

Two studies were conducted to simulate as close as possible real practice dynamics to evaluate the labeling effectiveness. In each study, a mock prescription order and final packaged product was handed to a pharmacist in their own setting and they were given a reasonable period of time to “fill the prescription”. The study monitor collected the filled prescription, scored the results as correct or incorrect, and took observations of pharmacist behavior while setting and locking the device. An initial study of one hundred and one retail pharmacists was performed to test labeling comprehension.

As shown in Figure 2, the initial study (Study 1) demonstrated a 42% rate of dispensing error, signaling a need for labeling revisions to the outer box and instructional labeling. Following label revisions and beta testing of the revised articles as part of the design control process, a second study (Study 2) was performed with fifty retail pharmacists to measure effect of the labeling changes with dispensing pharmacists. The comparative results for study 1 and 2 are shown in Figure 2. The error rate from study 1 to study 2 declined from 42% to 8% based on the effect of labeling changes.

Case 2: Patient Self Administration with a Novel Drug Delivery Device

A pharmaceutical company had developed an adjustable dosage delivery device for an approved medication to treat a common disease. The device was developed to offer patients more convenience and portability of dose administration and potentially more accurate dosing. Prior to use, the device required priming and setting of the patient specific dose by the patient or caregiver. The device was initially set at an arbitrary default dosage.

Three product use trials were conducted with pre-registration materials. An initial study with forty patients was performed to test labeling comprehension and product usability with the target patient population. This study (blue bars in Figure 3) identified several issues with label comprehension with just 31% performing device setup correctly and only 67% correctly administering doses from the device. As a result, labeling revisions were made to the device and instructional insert, and a second study was conducted with forty-one patients to retest label comprehension and product usability. This study (red bars in Figure 3) demonstrated improvement, however the results remained unsatisfactory. More significant labeling and instructional insert changes were made by the pharma company, and a third study with 20 subjects was conducted to confirm the improved efficacy of the labeling revisions. The comparative results for studies 1, 2 and 3 are given in Figure 3. A dramatic improvement was observed from study 1 to study 3 with overall error reduced in half or more for each key measure, including a 95% success rate with dose administration in the last study.

5. Discussion

BioTrak has conducted other studies similar to those reported here with initial study observational product use error rates typically in the in the range of 40-70% for respondents naive to a novel drug delivery device. Sponsors are often shocked at these findings which suggest far greater label comprehension issues than what can be estimated from calls and complaints to medical affairs departments. A well designed labeling comprehension study is not an expensive proposition, most study designs can evaluate labeling materials with 40-100 subjects before and 40-100 subjects after label revision. These studies demonstrate the benefit of conducting label comprehension studies as a means for improving product safety, efficacy, and usability.

6. Conclusions

A well designed mock trial where product use is simulated has in our experience correlated well with actual field results. Such studies can provide a significant reduction in product use errors with the potential outcome of improved safety, efficacy, and competitiveness. Early testing of proposed labeling can identify problem areas in label comprehension that lead to a potential medication or administration error and/or frustration with product use. Such studies validate design control, quality of labeling and can facilitate the product registration process.

For more information contact BioTrak at 760 448-4823

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