META ANALYSIS

Increasingly nowadays, we find ourselves in situations in which we need to make a conclusion based on the results of different and differing studies.

For example, we may be asked to review the literature and the results of unpublished studies conducted by another firm. Based upon what we find, we may be asked to recommend for or against licensing a product from another firm. Or one may want to determine if she wishes to continue taking synthetic estrogen, given the latest research result on how it affects breast cancer and heart disease. Ever put yourself into the shoes of a FDA reviewer making a determination on whether to approve a drug or device based upon the studies submitted in an NDA?

What about cold fusion? Many prestigious investigators can’t replicate the results of Ponds and Flieshman; yet others claim to have reactions that have been running for months, if not years. What is your take?

Meta-Analysis is a systematic method for synthesizing the results form independent studies. In my reading, it has primarily applied to clinical studies. It borrows heavily form the areas of expert review and multi-center trials. It essentially treats each of the independent studies as if they were individual centers in a multi-center study. A Meta-analysis looks at three factors:

Is there any publication bias? (Do positive results tend to get reported more than negative ones?)
An assessment of the quality of the studies being considered for combination.
Are the results of the studies similar? (In statistical terms, are the results homogeneous?)

Want to know a little more? Stay tuned. There is also a nice discussion with references in

Fisher and van Belle, Biostatistics A Methodology for the Health Sciences, 1993, John Wiley & Sons, New York, NY.

Earl S. Johnson PhD

Director of Biometics

TEAM WORK - AN EXAMPLE FROM NATURE

One of the "buzz words" these days is teamwork. Since none of us operates in a void and effective work within teams is essential to success in this industry, I thought I would share the following lessons from nature about the teamwork of geese.

As each goose flaps its wings, it creates an "uplift" for the following bird. By flying in a "V" formation, the whole flock adds 71% greater flying range than if the bird flew alone. LESSON 1: People who share a common direction can get where they are going quicker and easier because they are traveling on the thrust of one another.

Whenever a goose falls out of formation, it suddenly feels the drag and resistance of trying to fly alone, and quickly gets back into formation to take advantage of the "lifting power" of the bird immediately in front. LESSON 2: If we have the sense of geese, we will stay in formation with those who are headed where we want to go (and be willing to accept their help as well as give our help to others).

When the lead goose gets tired, it rotates back into the formation and another goose flies at the point position. LESSON 3: It pays to take turns doing the hard tasks and sharing leadership – with people as with geese, we are interdependent upon each other.

The geese in formation honk from behind to encourage those in front to keep up their speed. LESSON 4: We need to be sure our "honking" from behind is encouraging, and not something else.

When a goose gets sick, wounded or shot down, two geese drop out of formation and follow it down to help and protect it. They stay with the wounded or ill goose until it is able to fly again or dies. They then launch out on their own, with another formation, or catch up with the flock. LESSON 5: If we have as much sense as geese, we too will stand by each other in difficult times as well as when we are strong.

Glenda Guest

Clinical Research Associate

A SOUP TO NUTS POST-MARKETING 306 PATIENT TRIAL IN LESS THAN 10 MONTHS

Part 1

We here at NCRA are quite proud of a post-marketing device trial (306 patients recruited from 7 sites across the US) that we completed from protocol inception to final report, and we did it in 9 and a half months!

Depending on the complexity of the trial, in the past, such a trial could have taken up to 40 months, but today companies are demanding, and receiving, much tighter timelines as they compete for their share of the market. Whether it be a post-marketing trial or a trial supporting an NDA or PMA, the need for completing the trial within a defined timeline is of paramount importance to both the Sponsor and their chosen CRO. For example, in 1997 the ACRP White Paper on Future Trends: Their Impact on Sponsor CROs & Investigative Sites reported that for each extra day a product is delayed to go to market, it costs 1.3 million dollars. Even though ours was a post-marketing trial, the process we will describe here and in Part 2 (more to come!) can be applied to most any regulated Clinical Research trial.

KEY POINTS:

· The use of DataFax™ as the primary data collection and trial management tool.

· Integrated team work within the CRO, with the Investigative Sites and with the Sponsor (yes that old cliché again –Team Work!).

· Communication within the team (don’t forget, the Sponsor is part of that team – CROs can not effectively work within a vacuum).

· Biometrics as part of the process from the very beginning.

· A Project Manager or primary contact point for both the CRO and the Sponsor.

· And last but not least, dedicated, knowledgeable research personnel willing to go that extra mile!

TIMELINE

1^st Draft to Final Protocol, Investigator Recruitment & IRB Approvals	2.75 Months
First to Last Site Initiation	1.00 Month
In-Life Portion of Trial	2.75 Months
Last Patient out to Database lock	1.5 Months
Analysis & Sponsor Approved Final Report	1.5 Months
TOTAL	9.50 Months

For our Part 2 we will provide further details on the process itself!

A SOUP TO NUTS POST-MARKETING 306 PATIENT TRIAL IN LESS THAN 10 MONTHS - PART 2

In Part 1, we discussed the key points that made our trial so successful. In Part 2, we will describe in greater detail several of the key points that were previously noted in Part 1.

· The use of DataFax™ as the primary data collection and trial management tool.
DataFax is a software package that utilizes Optical Character Recognition (OCR) to collect and clean data. The CRF is faxed into the Central Data Management Center where it is automatically entered into the system. Personnel then review the data checking for consistency, comparing the fax image to the OCRed data fields, and noting any areas that require “clean-up”. The system allows for either automated or customized queries that are then faxed back to the site. In this manner the data is entered and cleaned on a real time basis. No having to drag those medical records out of Medical Records, or worse yet Archiving, because its been such a long time between when the data was first collected to time of review for query resolution. DataFax also provides standard and customized study conduct reports such as overdue visits, patient enrollment status, clean versus dirty CRFs, number of outstanding queries, etc. In this way the Project Managers from both sides can be kept up to date on all aspects of the trial, allowing them to intervene quickly as issues arise. This allowed us to have the queries for all 307 patients resolved within 1.5 months from the last patient/last observation to locking of the database.

· Biometrics as part of the process from the very beginning.
Many times Biometrics personnel are included in the process when it comes time to analyze the data. Other times they may be part of the protocol process, but their work doesn’t start until time for analysis and the final statistical report. Based on the study’s objectives, our biometrician was able to generate realistic dummy data based on the DataFax files and then use it to write and debug the analysis programs. He also constructed data display tables to look for any problems that could be resolved while the study was underway. In this way, once the database was locked, he was quickly able to unblind the study, set up treatment groups and run the programs in a few weeks, so that a final report was ready within 1.5 months from database lock.

· A Project Manager or contact person for both the CRO and the Sponsor.
In this case, NCRA provided the Project Manager and the Sponsor a contact person. It’s important to note that just having a Project Manager and a contact person is not all that’s needed to keep the ball rolling. Both those people also need to have either the authority to make decisions or at the very least, have direct and immediate contact with people that can make decisions related to study conduct and process. Also, it’s necessary to have regular communication utilizing any preferred media, as long as each person has access and is comfortable with frequent contact, sometimes on a daily basis.

By using these methods, we were able to conduct our post-marketing device trial, Soup to Nuts, for 306 patients in 9 and 1/2 months, and with good planning and hard work, you can too!

It’s coming…Year 2000 Flu Season. Time to start thinking about your Flu Vaccine.

WHO BENEFITS FROM THE VACCINE?

New CDC recommendations state that individuals aged 50 or older and those with chronic medical conditions (such as diabetes, asthma, heart disease, etc.) are advised to receive the vaccine. Those aged 65 and older especially should get the vaccine! Illnesses such as these compromise the immune system and increase the risk of complications resulting from the flu.

Get it early, as it takes time for the body to build up immunity. Preferably several weeks before flu season starts (late October/early November). The CDC advises that the flu vaccine supply may be later than usual this year, but in time for mid-October through December immunization.

If you are allergic to eggs, do not get the vaccine. Eggs are used in the making of the vaccine.

As always, you should consult your own physician, and you may want to ask if you should be getting a Pneumovax (for prevention of pneumonia), particularly if you are 65 or older and have not yet gotten this one in a lifetime protection.

YEARLY VACCINATIONS

Flu viruses differ from year to year, making it important to get your flu vaccine yearly.

CAUSES

The flu is a severe respiratory infection caused by a virus. When a person sneezes or coughs, contaminated airborne droplets of respiratory fluids are dispersed into the air, and possibly onto nearby surfaces.

WHERE TO GET THE VACCINE

Contact your doctor, nurse practitioner, physician assistant, or your local health department for specific dates and times.

PREVENTION

Wash hands OFTEN. Definitely one of the most effective and easiest ways to escape contracting the flu (or a cold). Note: use hand lotions for dry or chafing hands resulting from increased washings.

Consume extra water. Water is essential to human life, and assists the body in maintaining general good health.

During the flu season, avoid crowds.

SO, YOU GOT IT ANYWAY

Rest and drink plenty of fluids. Drinking additional water keeps the mucus membranes moist and can help control cough. Juice is good too.

Extra bed rest will facilitate your recovery – and protect others from your germs.

An over-the-counter pain reliever will reduce fever and any other physical discomfort. (Acetaminophen is safe for children and the elderly, and ibuprofen is generally suitable for both children and adults.) Be sure to follow recommended dosages as indicated on the package – or by your healthcare professional.

Cool compresses can help decrease fever and increase comfort.

A warm salt-water gargle (natural treatment) or throat lozenge will provide quick, but temporary relief of throat pain. A lozenge may also reduce the impulse to cough.

Irritated and dry nasal and throat membranes may benefit from the moisture of a humidifier or vaporizer.

SYMPTOMS

Muscle aches and pains, fever, dry cough, stuffed nose/congestion, runny nose, headache and fatigue.

* * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * *

As flu season approaches, we sincerely hope that you and those around you are fortunate enough to evade the dreaded “flu bug”, we also hope that the information presented here is helpful and informative.

Moving Beyond Subject Recruitment to Retention

I recently attended an industry conference and would like to share with you some of the thoughts and ideas from one of the sessions. The presenters provided information about the importance of subject retention for trial participation.

Subject recruitment and retention are factors that effect every study, be it for a pharmaceutical, medical device or nutritional supplement product. Efficient recruitment paired with effective and pro-active retention activities will enhance the success of your product development activities.

Broad points to consider include:

· Many companies plan to “over enroll” for their trials to compensate for poor subject retention. Few focus resources “up-front” on retention issues, citing increased costs as a reason.

· Subjects participate in clinical studies for many different reasons, e.g., they feel they will gain access to the “best medicine available”, “the newest treatments”, “free treatment”, or will “help advance science”. Understanding the reasons can help us to increase subject retention.

· Subject satisfaction correlates with subject retention.

· PI = Practically Invisible (rather than Principal Investigator) for too many sites. This factor can influence subject retention negatively. Surveys indicate that subjects in studies want to see the PI.

· 8 of 9 physicians over-estimate recruitment abilities, and 50 – 75% over-estimate retention abilities.

· Subject surveys, even “anonymous” surveys (sent to the CRO vs. the PI, Site, or Sponsor) can be very useful. You can learn why subjects are participating in your trial (or why they dropped out) and then take steps to meet their expectations and increase retention rates. The information can be used to help train investigative sites to better meet their subjects’ expectations.

· A subject’s perception of your institution, even a past negative experience with an individual, or their interpretation of press releases about previous studies done at your institution can have a negative impact on current enrollment. (“I don’t want to be their guinea pig”, “I would join the study, but ‘that lady’ has always been so rude to me”, etc.).

· 47% of our nations 191 million adults read at marginal levels or below. Subjects may be embarrassed to ask for explanations of informed consents, or for help in filling out diaries or paperwork.

· Allow ample time between explaining the informed consent and signing it, this can help limit dropouts due to impulse sign-ups.

· A subject’s perspectives of participation in a clinical trial may be that the primary objective is to receive medical care. Investigators may view completion of the trial as the primary objective, with the medical care as the means to that end. This difference in paradigms can affect retention.

· Addressing subject recruitment and retention strategies with the Study Coordinator at a meeting held parallel to the Investigator meeting is recommended.

Many simple steps can be taken to assess subject expectations and enhance retention. Recruitment is the first important step, but effective retention can help save two of your most important resources: time and money. By retaining subjects in your study, you save subject compensation money and valuable time (the time you would have to re-invest by recruiting a replacement and keeping them enrolled long enough to complete the study). This effects the bottom line. Less money spent up front, and faster completion time means your product gets to market sooner and you earn a return on your investment as early as possible.

Data Entry in Clinical Trials

Part I

Data entry in clinical trials is the process of entering data into a computerized database or spreadsheet. Once the data is in a database it can then be manipulated into programs, e.g., statistical programs and clinical reports.

There are many different kinds of data collection used in clinical trials. Electronic data capture, web-based data capture, fax-based data capture and entries from hard copy case report forms are the most common.

In a fax-based system, the CRF is displayed in a split screen view (typically data above and fax below). The data entry person ‘accepts’ the record into the database and then compares the CRF image with the fax image. The OCR (Optical Character Recognition) software reads check boxes, numeric data fields, and visual analog scales. Text must be key entered manually. Data fields will be left blank if OCR encounters ambiguous entry, (e.g. more than one response checked where only one is allowed), or if it reads a numerical value which does not pass its legal values test. The OCR software will also make errors if numbers are not clearly printed inside the data boxes. The data entry person compares the CRF images against the fax images, corrects any errors made by the OCR and key enters any comments or text manually.

Data quality control in clinical trials is where we introduce the concept of double data entry. The process of double data entry can be implemented in several different ways, depending on the data collection software you are using for your clinical trials.

The most rigorous kind of double data entry is blind, independent, and third-person double data entry. This is where data entry is performed by two different people using the same data entry forms (Case Report Forms or CRFs), and where the content from the CRFs is entered by the second person without any cue from the first person. Finally a third person decides which entry is correct in the case of a discrepancy (if any) between the first and second entry.

The next kind of double data entry is to have two persons enter the same data but the second person gets a notification flag of a discrepancy relative to the data entered by the first person. This process is generally referred to as double data entry using data verification. Since the second person (who is usually more skilled, proficient) controls what is decided as the correct entry, this process can be considered less stringent, as the second data entry person can be biased to their own entry.

In a fax-based system, second sight verification is generally the process used for data quality control. Typically a second data entry person will retrieve all records and review them a second time looking for any errors made during the initial data entry.

The big question is whether double data entry really improves data quality. A lot depends on the SOPs (Standard Operating Procedures) implemented in your organization, but more depends on the way your data management department is ‘set up’. There are two basic kinds of set-up. In Part II of this article, we will discuss the different kinds of ‘set up’ and explore further nuances of data entry.

Data Entry in Clinical Trials

Part II

As noted in Part I of our article, there are two basic kinds of data management department ‘set up’:

The first is referred to as “Heads down” data entry. This is performed by individuals who have little training in the scientific content of the data they are entering. They are typically ‘clerical’ people with few skills and experience in clinical data management. They may have little exposure to clinical trials, medical terminology, etc.

The second is referred to as “Heads-up” data entry. This is performed by qualified individuals who have experience in clinical trials, broad knowledge in medical terminology, coding dictionaries, CRFs, how Data Coordinators work and record data, etc.

Data entry performed in a “Heads-up” facility may appear to cost more for the education, training, and experience required to get data entry done by qualified people. “Heads-down” facilities typically strengthen the process by hiring supervisors that have the equivalent experience of data entry personnel in a “Heads-up” facility. The actual costs of keyboarding may be lower when performed by clerical personnel but the overall process may actually be less costly in a heads-up shop because of the fact that data entry and data quality control are performed by the same personnel. A heads-up shop is also more likely to understand the importance of CRF design and where investigator sites stumble over CRF completion issues.

Of course, double data entry is usually not considered to be enough. Programs must be written to test data items (edit checks), review the output from these programs, issue queries, etc. This is where you usually get into the specifics of your organization, as in the software you use and the SOPs you follow. Some organizations also perform a visual comparison of the database listings against the actual case report form.

The industry, as a whole, performs double data entry to cut down on error rates. However, there is no uniform method to estimate data entry error rates. Do you count characters within a field or entire fields? Do you include comment fields? Should a weighting be applied to key fields? What if the database includes derived fields or pre-filled data? And if everyone does it differently, how do you come up with a true error rate? A 0.01% residual error rate does not ensure that the statistical analysis will be valid, especially if all the errors occurred within the primary data. Some people feel that data entry error rates are the wrong focus. Perfect data entry is worthless if the CRF data is garbage.

So what does all this mean? Our data management people have worked in both heads-up and heads-down shops. The heads-up shop is more efficient. The heads-down shop may save time up front, but costs a lot more time and money when you begin to ‘clean’ the data. We believe you should hire bright individuals willing to do data entry and that you should also give them responsibility for the project. Train them in the software in use, medical terminology, and allow them responsibility to interact with the monitors and/or investigator sites to resolve queries.

Data management staff needs to interact and get advice from the Biostatisticians. There should be no departmental boundaries – what is important for the analysis of the clinical trial? There is no need to spend more time checking data, writing validation checks, issuing queries, etc., for data items that are not relevant to the statistical analysis. How will the data be analyzed and what parameters are critical to the submission?

In conclusion, the value of double data entry may not be as important in a heads-up shop as long as CRF review is done and good edit check programs cover the important things. The design of the case report form is still the bottom line. Too many CRF designs collect too much data, or collect data that is useless, e.g. contains many comment fields, and will not even be analyzed.

The Pitfalls of Exhibiting

It is approaching that time of year again for companies to exhibit at conferences and tradeshows. As you prepare your plans and budgets for exhibiting, always prepare for unforeseen circumstances. Here are some examples of mishaps that companies may run into when they first start exhibiting.

Potential Problem 1: Setting Up and Breaking Down the Exhibit Booth

The first thing an exhibitor needs is a good booth. When choosing a booth, you need to make sure that the booth can be easily shipped and that it can be set up and broken down at a rapid pace. At many of the large conferences, there are guidelines that the exhibitor must adhere to. One of these is that union laborers must be used. For example, at some conferences you have 30 minutes for one person, and one person only, to set up and break down your booth. If it takes any longer, a conference laborer needs to be contracted at rate of $55 to $70 per hour, with a mandated one-hour minimum for both the setup and break down of the booth. As you can see, it pays to purchase or rent a professional booth that requires minimum set-up and that can be handled by one person.

Potential Problem 2: Shipping Materials from the Conference or Tradeshow Back to the Exhibitor or Rental Agency

Some of the larger conferences also "highly recommend" that you utilize their shipping services. If you do not, you are solely responsible for seeing that your booth and miscellaneous materials get shipped back to your facility, regardless of what is promised. At first glance, this seems easy enough to accomplish, but the reality can be something quite different.

We know of one instance where an exhibitor was told that the convention service would take care of removal and shipping of the materials that had been set-up to be sent via FedEx, even though FedEx was not the conference service's preferred shipping service. The exhibitor had packaged the booth and materials, properly addressed the packages and left FedEx slips already filled out with their account number recorded. When they went to query on how to get them sent out, they were told that a conference laborer would take care of seeing the items got shipped. The exhibitor thought this was reasonable, since they had already paid for a one hour break-down labor fee where the laborer had never shown up at the agreed upon time, so instead break-down had been done by the exhibitor. The exhibitors left the exhibit hall thinking everything was under control.

Many days later the materials arrived back in-house. The exhibitor was surprised to discover that the convention service had instead shipped it via another carrier at an exorbitant cost. That shipping company had a minimum charge based on 100 lbs. The boxes being sent back weighed well less than 100 lbs., but the exhibitor still ended up paying over $100 per box shipped. Some of those packages would have cost them less if they had left the materials there and had them reprinted. The rental booth did not get back to the rental agency within the ten-day rental period and the exhibitor was charged an additional fee for late return. To add insult to injury, along with arriving late, the rental company received the booth with a COD due which the exhibitor had to reimburse. It took the exhibitor many man hours, expense and considerable aggravation to straighten out the resulting mix-up.

As you can see, it pays to take the time to do extensive research into your particular conference's or tradeshow's rules as they pertain to set up, break down and shipping, or you can find yourself going over your allotted conference budget at the end of the day. Add to that the frustration of "learning" the hard way and your conference can turn into a very large headache. For new exhibitors, we hope this information will be helpful in preparing to counter some of these costly and 'hair pulling' problems. Next month we will address other things to plan for when you are new at exhibiting, such as "giveaways" and other miscellaneous costs and how these can impact on your conference budget.

The Pitfalls of Exhibiting Part II

Last month we noted that it was approaching that time of year again for companies to exhibit at conferences and tradeshows. We spent some time discussing areas of concern that arise when actually exhibiting at the shows. This month we want to touch on those expensive giveaways you spend so many agonizing hours choosing.

For anyone who has been to a tradeshow, you know that giveaways are frequently used to draw in the customer. Giveaways can vary from pens to palm pilots, and what you choose should be based on a number of considerations.

1. Do you want to saturate the market with your name and logo by giving away many small items, or do you want to reserve special gifts for potential clients only. You may make this decision depending on your particular market and the presence your company currently holds. If you are a brand new company, there is something to be said about saturation. If you’re well known with a good track record, you may be seeking certain types or sizes of companies when you going looking for potential clients.

2. Cost is always a substantial factor. You can choose to give away one or two expensive gifts, or give away smaller gifts in order to reach more potential clients. Another option is to do both, depending on your potential audience and whom you are trying to reach.

3. Local and regional laws are another consideration. For example some countries apply limits on the value of the giveaways.

4. Another thing to keep in mind is shipping the giveaways to and from the show. When you’re working up your budget remember to include shipping costs. Also remember that the people attending have limited space in their luggage. While some giveaways seem like a great idea, if it is not something they can fit in their luggage, your potential client may quickly discard it. Research has shown that up to 80% of giveaways and literature collected at tradeshows never makes it home.

5. You may want your giveaways to reflect your logo and/or telephone number, and be something they will use in their office. This increases your advertising “bang for your buck”, as it is a good possibility that others in the office will also be reminded regularly of your presence as they view and use their peers’ tradeshow gifts.

Finally, even though giveaways are utilized frequently at tradeshows to pull the customer in, don’t forget that at the end of the day your services or products and how they are presented will be what sells for your company. So even though you spend considerable time and money purchasing those giveaways, the greatest “giveaway” you can supply your potential clients is someone to speak intelligently to them about what you have to offer. When choosing who you want to represent you at the show, always bear this in mind and look for staff who are comfortable interacting with people.

We hope these two “tidbits” have been helpful when planning for your shows.

Good Luck and Happy Exhibiting from NCRA!

Common Medical Device Clinical Study Delays

(And tips on how to avoid them)

Medical Device companies operate in a highly competitive environment. Delays in clinical development result in lost revenue as well as competitive disadvantages. The clinical development life cycle of devices involves developing a product from the conception stage to reality, moving through clinical trials to approval and executing market release. While maneuvering through this process, you can discover that all too soon, your product can become obsolete. This means limited time to recoup your development investment and realize a reasonable profit. Consequently, device manufacturers need to balance speed with quality and compliance issues to successfully execute the clinical development of their products, and achieve the earliest possible release into the market.

Factors that lead to clinical study delays, and tips about how to avoid those pitfalls are summarized below.

· Protocol Development/Changes: Changes too late in the game effect your overall timeline.

AVOID BY:

1. matching your study objectives to your claims,

2. using successful protocol templates,

3. communicating with the FDA,

4. using your physician advisors,

5. sacrificing non-critical indications if necessary.

· Slow Patient Enrollment: Considered to be one of the most common reasons for clinical study delays. Enrollment is effected by competing studies at the site, inaccurate investigator predictions, and restrictive Inclusion/Exclusion (I/E) criteria.

AVOID BY:

1. carefully setting your I/E criteria,

2. obtaining study coordinators’ input on I/E criteria prior to FDA submission,

3. selecting sites carefully,

4. using IRB approved advertising,

5. multiplying investigator’s prediction of enrollment timelines by 3-4 times to get a better guide as to what actual enrollment will be.

· IRB Approval Delays: Delays in approval of site specific protocol and informed consents are costly.

AVOID BY:

1. obtaining schedules of IRB meetings for the next 6 months,

2. grouping sites by IRB when planning initiation dates for sites (allows you to start some sites even though others may be delayed),

3. using sites with previous good approval timeframes,

4. providing a sample consent,

5. using consent templates whenever possible,

6. giving consent on disc to each site,

7. working with an experienced CRO to assist in consent development,

8. anticipating changes to the consent form.

· Company Resources/Staffing: Changing priorities internally can leave you “in the lurch” for forwarding your development plans.

AVOID BY:

1. setting realistic goals,

2. establishing and maintaining schedules and projections,

3. communicating with stakeholders regularly (especially regarding staffing needs),

4. hiring a qualified CRO when internal staffing too short to meet needs,

5. keeping the trial as simple as possible.

· Site Issues: Changes in staff, lack of interest and competing studies all affect your development plans.

AVOID BY:

1. careful site qualification/selection,

2. ensuring therapy is of interest to your investigators,

3. conducting investigator meetings because they can spark camaraderie (have coordinator meetings too, to provide trial-specific instructions),

4. establishing good relationship with coordinators at sites.

· FDA Approvals/Changing Requirements: FDA review times, changing required data, etc., have negative development impacts.

AVOID BY:

1. establishing early communication with the FDA,

2. reviewing your investigational plan with a qualified statistician,

3. having pre-Investigational Device Exemption (IDE) meetings,

4. having no experimental outcomes (especially with new therapies),

5. including agency statisticians in FDA meetings.

· Device Reimbursement Issues: These issues can cause customers to choose a competitor’s product, and negatively effect your sales.

AVOID BY:

1. working with the reimbursement department to ensure accurate device classification,

2. supplying tools for sites to use to obtain reimbursement (such as contact names or reimbursement books).

· Product Performance Issues: Such issues can lead to recalls and/or need for modifications.

AVOID BY:

1. performing pilot/feasibility studies,

2. involving R&D early in the process,

3. thoroughly training clinical sites on proper use of your product.

We at NCRA encourage you to put these tips to work in helping you meet your clinical development objectives.

Is A National “Save All Stem Cells Program” Possible?

There are complicated controversies surrounding the issue of stem cell research. Many researchers believe stem cell research is necessary to find cures for diseases that currently can cause the death of millions of our citizens. Popular celebrities, ill with diseases for which stem cell research offers promise of a cure, champion their cause, making public their pleas for changes regarding obtaining stem cells for research. Opponents of fetal or embryonic stem cell use also passionately argue their concerns.

We recently read an article that we would like to share. It appears that further dialog in this area may lead to identification of mutually acceptable sources for obtaining and preserving stem cells. These could then be used for many life-enhancing purposes, research being just one of the areas that could see a benefit.

TOTAL

CAUSES

WHERE TO GET THE VACCINE

PREVENTION

Data Entry in Clinical Trials

Part I

Data Entry in Clinical Trials

Part II