Automated Selection of Patients for Clinical Trials

Eugene FinkLawrence O. Hall

Dmitry B. GoldgofBhavesh D. Goswami

Matthew BoonstraJeffrey P. Krischer

A clinical trial is an evaluationof a new treatment procedure.

Clinical trials

When physicians conduct a trial, theyrecruit patients with matching healthproblems and medical histories.

Selection of patients

The selection of trial participants isa manual procedure, and physiciansmay miss eligible patients.

• Gotay [1991] demonstrated that physicians choose only 39% of the eligible patients

• Fallowfield et al. [1997] showed that they choose less than 50% of the eligible patients

Expert system

We have developed a system thatautomatically selects prospectivetrial participants.

Outline

• Knowledge base

• Selection results

• Cost reduction

Knowledge base

• Tests and questions

• Eligibility criteria

Tests and questions

ExampleMammogram, $150What is the cancer stage?Does the patient have invasive cancer?Biopsy, $400How many lymph nodes have tumor cells?What is the greatest tumor diameter?

The knowledge base includes a list of medical tests. A test descriptionincludes a dollar cost and relatedquestions about a patient’s health.

Eligibility criteriaThe knowledge base also includeslogical expressions that representeligibility for the available trials.

AND

cancer-stage {II, III}

OR invasive-cancer = NO

lymph-nodes 3

tumor-diameter 2.5

Example

Selection process

The system collects data until it candetermine whether the eligibilityexpressions are TRUE or FALSE.

If patient records do not provideenough data, the system identifiesthe required medical tests.

Outline

• Knowledge base

• Selection results

• Cost reduction

Experiments

We have used fifteen breast-cancertrials at the Moffitt Cancer Center.

• Past data from 187 patients

• Current data from 169 patients

Finding eligible patients Past data for 187 patients

ClinicalTrial

Parti-cipants

OtherEligible

10822108401107211378119921210012101

10 .

0 .

48 .

4 .

5 .

8 .

20 .

5 .

19 .

26 .

19 .

6 .

20 .

30 .

Finding eligible patients Current data for 169 patients

ClinicalTrial

Parti-cipants

OtherEligible

11132119311197112100121011238512601126431275712775

4 .

2 .

4 .

0 .

11 .

0 .

0 .

16 .

1 .

23 .

1 .

26 .

0 .

5 .

52 .

19 .

1 .

36 .

3 .

17 .

Participation in other trials Current data for 169 patients

ClinicalTrial

Incom-patible

Compa-tilbe

No OtherTrial

11132119311197112100121011238512601126431275712775

0 .

0 .

0 .

0 .

13 .

8 .

0 .

0 .

0 .

3 .

1 .

11 .

0 .

1 .

6 .

2 .

0 .

10 .

1 .

3 .

0 .

15 .

0 .

4 .

33 .

9 .

1 .

26 .

2 .

11 .

Summary

The results suggest that the systemcan increase the number of trialparticipants by a factor of three.

Outline

• Knowledge base

• Selection results

• Cost reduction

Medical tests

The selection of trial participantsmay require medical tests.

• The total cost of tests may depend on their ordering

• Finding the right ordering is often a complex problem

Ordering of tests

The system chooses the ordering of teststhat reduces their expected total cost.

The ordering is based on the test costs,number of trials that require each test,and structure of eligibility expressions.

After getting the results of the first test, itrevises the ordering of the remaining tests.

Cost reduction Past data for 187 patients

ClinicalTrial

Mean CostW/O Test

ReorderingWith Test

Reordering

10822

11072

11378

$70 .

$209 .

$35 .

$11 .

$60 .

$19 .

Cost reduction Past data for 187 patients

$0

$250

$200

$150

$100

$50

10822 1137811072

W/O ReorderingWith Reordering

Cost reduction Current data for 169 patients

ClinicalTrial

Mean CostW/O Test

ReorderingWith Test

Reordering

11971

12601

12757

$192 .

$36 .

$107 .

$192 .

$3 .

$107 .

Cost reduction Current data for 169 patients

$0

$250

$200

$150

$100

$50

11971 1275712601

W/O ReorderingWith Reordering

Conclusions

We have developed a system thatselects prospective trial participants.

• Helps physicians to identify eligible patients

• Can increase the number of trial participants

• Can reduce the cost of the selection process

Future work

• Deploy the system at the Moffitt Cancer Center

• Evaluate the satisfaction of physicians and nurses

• Add probabilistic reasoning