Best Practices Spotlight

Make study start-up a smooth-sailing process

Keep documents up-to-date

Everyone in the clinical research industry has heard the dismal statistic of how one out of five clinical trial sites never enroll a single patient. Many physicians have been drawn to doing a study in addition to their fulltime clinical practice, and they often decide to give this up after one or two trials.

So what makes a small physician's practice successful in the research business?

"In order to be successful, the most important thing is to be well organized and have a very efficient site start-up process," says Arthur Waldbaum, MD, clinical investigator at Downtown Women's Health Care in Denver, CO.

Waldbaum has a one-doctor private ob-gyn practice. He's been in private clinical practice since 1978 and has done research since 1988. The majority of his more than 120 studies have been in the top 50% and often the top 10% to 20% in enrollment, he says.

"I gradually started doing more research, and over the last 15 years, I primarily do clinical research with less general ob-gyn," he says.

There have been many challenges with his research business, and Waldbaum has been a hands-on manager who likes to do the work efficiently and on time.

"There are advantages to having a smaller practice, as well as to being more efficient in doing it," he says.

When Waldbaum began running clinical trials, there was an occasional study, but it's different now, he adds.

"It's much different when you are doing 10 to 20 studies at a time, which is what we're doing now," Waldbaum says. "You have to be a lot more organized and efficient in doing the study start-up process."

Waldbaum has developed best practices over the years, including these tips:

• Put documents in place: "The first element is to make sure all documents are in place, all regulatory documents, so you get IRB approval in a timely fashion," he says. "And make sure you complete all the documents and have CVs and medical licenses up-to-date."

Each study has its own regulatory documents, and each IRB has its own specific forms to be completed. Waldbaum typically uses a central IRB.

Investigators and clinical research staff should prepare well for creating advertisements and using telephone screening questionnaires before they obtain IRB approval.

• Meticulously prepare budget and contract items: "There's nothing worse than being ready to start the study and going to the investigator meeting and not having your contract set or budget set, so you're starting to work on those then," Waldbaum says.

"You need to make sure you have developed a budget in advance and have all the line items there, so you know it will be profitable to do the study," he adds.

Waldbaum has a list of items he needs to negotiate for the budget, and he knows from experience what to look for in contracts. Examples of items to include in a budget are these:

— payments for line items

— ancillary services

— start-up fee

— initiation payment

— amount withheld

— frequency of payments

— advertising budget

— how screen failures are paid.

"I use a checklist because I don't want to lose any of those items," he says. "If you have those budgetary items outlined in advance and you make sure you have the required insurance requirements, then you're comfortable," Waldbaum says.

This is a necessary, if time consuming process. Waldbaum typically spends several days going over this list with the study template and budget.

"Before I go back to the company, I need to know what to ask for," he says. "Then it's a process of time and how much negotiation is needed between the sponsor and site."

Investigators should remember that whatever budget is presented by the sponsor has room for negotiation, he adds.

• Prepare office and staff for the study: "Hopefully, even before the investigator meeting, you should make sure everything in the office is prepared for the study," Waldbaum says. "We need to know which laboratory will be used, what type of equipment they need to make sure all equipment has been recently calibrated, and they need to make sure couriers — whether its UPS or FedEx — are in place."

The research site should have a primary coordinator and a back-up coordinator for the study. And their documents should be in order, showing the proper training for hazardous waste and human subjects protection, he adds.

"Make sure your site has the proper storage space and freezers, refrigerators, so forth," Waldbaum says. "This is so we don't find out later on that we don't have space for the drug or encounter anything that might delay the process once we're ready to start."

• Begin recruitment as soon as the IRB issues its approval: "If we have the IRB approval, I like to start looking at subject recruitment before the meeting starts," Waldbaum says. "We look into our database of patients and previous study participants to see of any would qualify for this type of study, and we'll even start calling and sending out letters to patients in our database so we'll have subjects lined up in advance."

Waldbaum also will begin creating an advertising plan, making decisions about whether to run ads on local media and which venues to use.

"We'll start preparation on which types of venues we think would be more beneficial for this type of study, and all of those can be done in advance, as well," he says.

"Once we know how much is in the advertising budget, some of the decisions we'll make are based on the budget, and some are based on the age of the study's subjects," he adds. "For younger subjects, we might do more Internet advertising, and for older subjects, we'll run ads in newspapers and on TV."

• Attend the investigator meeting: "Be sure you and your coordinator attend the investigator meeting," Waldbaum advises. "In some cases the investigator doesn't go to the meeting, or the coordinator doesn't go, and that delays the process because the sponsor will have a separate site visit scheduled before starting the trial."

"You will want all of your questions answered, including what the study timelines are and what you need clarified about the inclusion/exclusion criteria."

The investigator meeting is a good opportunity for learning more about the study's nuances, such as the enrollment criteria.

"There's nothing worse than screening patients and bringing them into the office and then finding out they don't qualify based on something in their history," Waldbaum says.

So the key is to write a precise screening script that includes any inclusion/exclusion details explained at the investigator meeting.

• Follow-up on loose ends: Although Waldbaum's research site is small, he makes certain he has fulltime research coordinators who are well-trained and can handle the new study.

"I don't do PRN staff; I have not found that to be very successful," he says. "Research coordinators are very important for each study, and they do a lot of work."

Waldbaum will not start a study unless he has the proper staffing to deal with it.

There might be a few additional documents to complete, and the site might have to create a source document, although sponsors typically provide this, he adds.

"The coordinator and principal investigator may have to do online training to make sure we know how to use the electronic CRF," Waldbaum says. "But other than familiarizing ourselves with all the documents and being more active in getting ads in place, we can begin more actively screening patients and should be ready to start enrolling at that point."