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Clinical Control...

You would not start to build a house without drawings. But many clinical trials are started without fundamental documents. Later those involved wonder why the clinical trial fails to establish acceptable proof. The reason is simple. You would never trust a schoolboy to grade his own book report. Such an evaluation must be protectored. Like the example, Clinical Trials must be protectored . If a clinical trial is not protectored, it usually becomes simply a clinical experiment not a clinical trial. The difference is that: in a trial, the judge is NOT supposed to care what the outcome or have a stake in the outcome. The judge is concerned as to the correct adherence to proper procedure. The procedures are created by a higher authority.

In a clinical trial only too often - much of the plan, protocol, training, forms, controls, techniques, records and final calculations are not considered and simply left up to the principal investigator to produce at their pleasure. This reduces the entire effort only an experiment and not a clinical trial. If the principal investigator is the highest authority, the clinical trial is merely an experiment. An experiment moves a hypothesis to a theory by adding new information. A clinical trial establishes a certain affect is generated on each occasion the affect is applied. The emphasis in a clinical trial is on repeatability..

In a clinical trial, the role of the principal investigator is to conduct the trial, not to evaluate the results. In fact, the principal investigator should not have access to the results. The results should be collected by the monitor and sent to an account who then tabulates the data. The clinical trial is flawed if the principal investigator receives any information (until the end) that suggests the clinical objective is being proved or disproved. The clinical trial is flawed if the trial is conducted then the decision is made how to calculate the data. The clinical trial is flawed if the same people who conduct the trial, calculate the results.

If the clinical trial is planned and executed properly (all documentation created prior to the start that will guide the conduct of the trial) then if all the papers are placed in a box and sent to another distant location another group of qualified people could conduct the clinical trial and obtain the same records! Emphasis: records. From the records, the results would be obtained. If one group kept records different from the other group that demonstrates that the clinical directives are either incomplete or not being followed.

A properly designed clinical study results in a protectored process that removes discretion away from the principal investigator and simply allows the principal investigator to investigate.

About three years ago, we saw what appeared as a very authenticate clinical trial. It was completed before we were hired. The clinical trial findings were summarized in beautiful graphs and calculations. The FDA requested the actual raw data (patient data). When these were delivered, 100 sequence numbers were missing out of about 800 sessions. The Principal Investigator had arbitrary discarded these sessions because the equipment had failed (ran out of batteries) during a testing session. He consulted no one. His actions were to protect the remaining data. The problem was, there was no protocol for that eventuality. The 100 that were discarded contaminated the original patient pool. That rendered the results inaccurate.

A Clinical Trial must be repeatable. If a different group of trained professionals followed the same instructions would they select the same type of patients and achieve a set of records that would be interrupted the same? A clinical trial performed at one site has significantly less creditability that if the same clinical trials are performed at three sites and the same results are obtained. Of course this should consider the level of risk.

Whether this clinical trial is conducted in Canada, England or the United States, good science dictates that you must develop, establish and demonstrate the effectiveness of this device to a medical certainty on a repeatable basis. How can you repeat it if you did not document each detail? Typically, a clinical trial for a medical device may be as few as 85 patients. Trials may be required at either one or site three sites (85 patients each). Patients must be selected to include the effects of biological diversity. This would be a double blind study where both normal and diseased states would be included without the investigators knowing and the device would be both functional to deliver the treatment and modified to not deliver the treatment. The instrument would have to demonstrate the ability to effectively treat patients to substantial the exact, limited, narrow clinical design that forms the clinical objective.

Each clinical trial should meet these basic requirements:

1. State the goal of the clinical study in a single comprehensive sentence.

2. Describe the patient group that this trial covered. Include biological diversity {variations in patient age, weight, and condition}.

3. Describe Clinical Trials which have been completed on this medical device and reason for more.

4. What alternatives exist to such treatment and was patient advised as to such alternatives.

5. Was patient counseled as to risks and did patient give an "informed consent".

6. Describe the records which were maintained to detail the Clinical Trial.

7. Over what period of time were these trials conducted.

8. Describe the follow up analysis of patients to authenticate the initial conclusions.

9. Where were the trials conducted; under who's authority {detail those involved}.

10. Detail over what period of time the trials were conducted, including all follow-ups.

11. Attach, include Clinical Trial protocol, test procedure and controls.

12. Include all data to describe each patient and the data obtained from the patient {avoid disclosing any confidential patient information, such as name, etc}.

13. Describe medical device used to perform the Clinical Trial. How does equipment differ from the equipment submitted in 510(K)?

14. What testing was performed on the medical device prior to the data gathering session to certify the calibration of the equipment prior to taking patient data?

15. What testing was performed on the medical device after the data gathering session to certify the calibration of the equipment prior to taking patient data?

16. What data was discovered as a result of this clinical trial?

17. What data was NOT obtained which became an objective for any subsequent Clinical Trials.

18. What results were discovered which were considered as improvements to the medical device.

19. Cite hardware/software elements in the final medical device which has benefited from this Clinical Trial.

20. Was the data obtained consistent with the data expected in the stated goal of the clinical study?

21. How does the data derived from this study compare to data from other studies?

copyright by Compliance Consultants, Stamford, CT USA, September 2001