Frederick Chen, MD, MPH

Despite the mapping of the human genome, the hundreds of millions of dollars invested in genetic research, and the hype about the transformation of basic science, physicians can be forgiven for questioning when—or whether—the genomics revolution will lead to improvements in patient care.^1,2 At press time, a glimmer of an answer appeared.

In January, the federal entity charged with evaluating the clinical usefulness of genetic applications recommended that patients with newly diagnosed colorectal cancer should be offered testing for Lynch syndrome,³ a rare inherited condition associated with an elevated risk for this type of cancer.

EGAPP’s first definitive recommendation

Aimed at reducing morbidity and mortality in relatives of colorectal cancer patients, testing for Lynch syndrome is the first definitive recommendation to come out of Evaluation of Genomic Applications in Practice and Prevention (EGAPP). The group, which is made up of clinicians and researchers steeped in evidence-based medicine, was formed in 2004. But until this January, EGAPP had issued only one report, in the fall of 2007.

In the 2007 report, EGAPP examined the usefulness of genetic testing for cytochrome P450 (CYP450) before prescribing SSRI antidepressants.⁴ (CYP450 is a genetic marker for liver metabolism of certain medications, including SSRIs.) Testing for this marker, EGAPP reported, was not ready for prime time. Actually, EGAPP said “I”—there was insufficient evidence to recommend for or against testing for this genetic marker.

In January, EGAPP issued 2 additional “I” ratings. The group found insufficient evidence to make a recommendation for or against both tumor gene expression profiling (eg, Oncotype DX) in women with breast cancer⁵ and UGT1A1 genotyping for patients with metastatic colorectal cancer being treated with irinotecan.⁶

Physicians are no strangers to the frustrating “I,” which leaves us pretty much where we were before the extensive evidence review and deliberation process began. We also tend to be a skeptical bunch. I suspect that most physicians take an “I” to mean a vote of no confidence, early adopters notwithstanding.

But “I” is an accurate reflection of the state of the evidence for the vast majority of genetic tests available today. Genomics should not get a free pass in today’s health care system, no matter how much money and marketing are devoted to it.

More than 1000 genetic tests, much uncertainty

The biggest problem facing EGAPP is the genetic testing deluge. There are already more than 1000 genetic tests on the market.⁷ And the excitement about genome-wide association studies (GWAS)—an approach that involves rapidly scanning for markers across the entire human genome to identify genetic variants associated with particular traits and diseases—promises to yield even more questionable clinical applications.

So what are physicians to do, faced with all of this uncertainty? The same thing we’ve always done. Use good clinical judgment, review the available evidence, cut through the hype, and practice medicine for the good of our patients.

Despite the mapping of the human genome, the hundreds of millions of dollars invested in genetic research, and the hype about the transformation of basic science, physicians can be forgiven for questioning when—or whether—the genomics revolution will lead to improvements in patient care.^1,2 At press time, a glimmer of an answer appeared.

In January, the federal entity charged with evaluating the clinical usefulness of genetic applications recommended that patients with newly diagnosed colorectal cancer should be offered testing for Lynch syndrome,³ a rare inherited condition associated with an elevated risk for this type of cancer.

EGAPP’s first definitive recommendation

Aimed at reducing morbidity and mortality in relatives of colorectal cancer patients, testing for Lynch syndrome is the first definitive recommendation to come out of Evaluation of Genomic Applications in Practice and Prevention (EGAPP). The group, which is made up of clinicians and researchers steeped in evidence-based medicine, was formed in 2004. But until this January, EGAPP had issued only one report, in the fall of 2007.

In the 2007 report, EGAPP examined the usefulness of genetic testing for cytochrome P450 (CYP450) before prescribing SSRI antidepressants.⁴ (CYP450 is a genetic marker for liver metabolism of certain medications, including SSRIs.) Testing for this marker, EGAPP reported, was not ready for prime time. Actually, EGAPP said “I”—there was insufficient evidence to recommend for or against testing for this genetic marker.

In January, EGAPP issued 2 additional “I” ratings. The group found insufficient evidence to make a recommendation for or against both tumor gene expression profiling (eg, Oncotype DX) in women with breast cancer⁵ and UGT1A1 genotyping for patients with metastatic colorectal cancer being treated with irinotecan.⁶

Physicians are no strangers to the frustrating “I,” which leaves us pretty much where we were before the extensive evidence review and deliberation process began. We also tend to be a skeptical bunch. I suspect that most physicians take an “I” to mean a vote of no confidence, early adopters notwithstanding.

But “I” is an accurate reflection of the state of the evidence for the vast majority of genetic tests available today. Genomics should not get a free pass in today’s health care system, no matter how much money and marketing are devoted to it.

More than 1000 genetic tests, much uncertainty

The biggest problem facing EGAPP is the genetic testing deluge. There are already more than 1000 genetic tests on the market.⁷ And the excitement about genome-wide association studies (GWAS)—an approach that involves rapidly scanning for markers across the entire human genome to identify genetic variants associated with particular traits and diseases—promises to yield even more questionable clinical applications.

So what are physicians to do, faced with all of this uncertainty? The same thing we’ve always done. Use good clinical judgment, review the available evidence, cut through the hype, and practice medicine for the good of our patients.

Despite the mapping of the human genome, the hundreds of millions of dollars invested in genetic research, and the hype about the transformation of basic science, physicians can be forgiven for questioning when—or whether—the genomics revolution will lead to improvements in patient care.^1,2 At press time, a glimmer of an answer appeared.

In January, the federal entity charged with evaluating the clinical usefulness of genetic applications recommended that patients with newly diagnosed colorectal cancer should be offered testing for Lynch syndrome,³ a rare inherited condition associated with an elevated risk for this type of cancer.

EGAPP’s first definitive recommendation

Aimed at reducing morbidity and mortality in relatives of colorectal cancer patients, testing for Lynch syndrome is the first definitive recommendation to come out of Evaluation of Genomic Applications in Practice and Prevention (EGAPP). The group, which is made up of clinicians and researchers steeped in evidence-based medicine, was formed in 2004. But until this January, EGAPP had issued only one report, in the fall of 2007.

In the 2007 report, EGAPP examined the usefulness of genetic testing for cytochrome P450 (CYP450) before prescribing SSRI antidepressants.⁴ (CYP450 is a genetic marker for liver metabolism of certain medications, including SSRIs.) Testing for this marker, EGAPP reported, was not ready for prime time. Actually, EGAPP said “I”—there was insufficient evidence to recommend for or against testing for this genetic marker.

In January, EGAPP issued 2 additional “I” ratings. The group found insufficient evidence to make a recommendation for or against both tumor gene expression profiling (eg, Oncotype DX) in women with breast cancer⁵ and UGT1A1 genotyping for patients with metastatic colorectal cancer being treated with irinotecan.⁶

Physicians are no strangers to the frustrating “I,” which leaves us pretty much where we were before the extensive evidence review and deliberation process began. We also tend to be a skeptical bunch. I suspect that most physicians take an “I” to mean a vote of no confidence, early adopters notwithstanding.

But “I” is an accurate reflection of the state of the evidence for the vast majority of genetic tests available today. Genomics should not get a free pass in today’s health care system, no matter how much money and marketing are devoted to it.

More than 1000 genetic tests, much uncertainty

The biggest problem facing EGAPP is the genetic testing deluge. There are already more than 1000 genetic tests on the market.⁷ And the excitement about genome-wide association studies (GWAS)—an approach that involves rapidly scanning for markers across the entire human genome to identify genetic variants associated with particular traits and diseases—promises to yield even more questionable clinical applications.

So what are physicians to do, faced with all of this uncertainty? The same thing we’ve always done. Use good clinical judgment, review the available evidence, cut through the hype, and practice medicine for the good of our patients.

BACKGROUND: Currently, most screening questions in the primary care setting address only alcohol abuse, but it is also important to screen for other substance abuse. The authors of this study examined the validity of a 2-question screening test for alcohol and other substances.

POPULATION STUDIED: The participants were 1252 patients randomly selected from 3 University of Wisconsin primary care clinics. They ranged in age from 18 to 59 years; 68% were women; and the population was racially diverse. Sixty-nine percent had private insurance. The prevalence of substance disorders in this study population was high (23%).

STUDY DESIGN AND VALIDITY: This prospective cohort study sought to identify 2 questions that could accurately screen for substance abuse. Screening questions were developed through a literature search and a series of focus groups. The interviewers asked patients the screening questions and then administered the Composite International Diagnostic Interview-Substance Abuse Module (CIDI-SAM), a series of questions based on the Diagnostic and Statistical Manual of Mental Disorders, third edition, revised used for identifying substance use disorders. The sensitivity of the screening questions was defined as the proportion of patients with a current substance abuse problem, as detected by CIDI-SAM, who had positive screening results. The high prevalence of substance abuse in this study will improve the positive predictive value of the screening test.This study was well designed and had a high response rate. Although the interviewers were not blinded while administering the screening questions and the CIDI-SAM, they were monitored closely, and a random subset of patients underwent urine drug testing. The authors also tested the validity of the screening questions with questions about patient comfort and truthfulness.

OUTCOMES MEASURED: The primary outcome measured was identification of either alcohol or drug abuse.

RESULTS: Among 1136 participants (91%), a positive response to either of 2 questions was 80% sensitive and specific for current alcohol or drug abuse. With the high prevalence of substance use in this sample, the positive predictive value of the 2 questions was 52% and the negative predictive value was 93%. Comfort with the interviewer was reported by 84% of the participants, and withholding any information by only 11%. Random urine substance screening of 231 patients revealed 14 positive test results in patients with a negative CIDI-SAM, but these results did not change the performance of the screening test.

BACKGROUND: Currently, most screening questions in the primary care setting address only alcohol abuse, but it is also important to screen for other substance abuse. The authors of this study examined the validity of a 2-question screening test for alcohol and other substances.

POPULATION STUDIED: The participants were 1252 patients randomly selected from 3 University of Wisconsin primary care clinics. They ranged in age from 18 to 59 years; 68% were women; and the population was racially diverse. Sixty-nine percent had private insurance. The prevalence of substance disorders in this study population was high (23%).

STUDY DESIGN AND VALIDITY: This prospective cohort study sought to identify 2 questions that could accurately screen for substance abuse. Screening questions were developed through a literature search and a series of focus groups. The interviewers asked patients the screening questions and then administered the Composite International Diagnostic Interview-Substance Abuse Module (CIDI-SAM), a series of questions based on the Diagnostic and Statistical Manual of Mental Disorders, third edition, revised used for identifying substance use disorders. The sensitivity of the screening questions was defined as the proportion of patients with a current substance abuse problem, as detected by CIDI-SAM, who had positive screening results. The high prevalence of substance abuse in this study will improve the positive predictive value of the screening test.This study was well designed and had a high response rate. Although the interviewers were not blinded while administering the screening questions and the CIDI-SAM, they were monitored closely, and a random subset of patients underwent urine drug testing. The authors also tested the validity of the screening questions with questions about patient comfort and truthfulness.

OUTCOMES MEASURED: The primary outcome measured was identification of either alcohol or drug abuse.

RESULTS: Among 1136 participants (91%), a positive response to either of 2 questions was 80% sensitive and specific for current alcohol or drug abuse. With the high prevalence of substance use in this sample, the positive predictive value of the 2 questions was 52% and the negative predictive value was 93%. Comfort with the interviewer was reported by 84% of the participants, and withholding any information by only 11%. Random urine substance screening of 231 patients revealed 14 positive test results in patients with a negative CIDI-SAM, but these results did not change the performance of the screening test.

BACKGROUND: Currently, most screening questions in the primary care setting address only alcohol abuse, but it is also important to screen for other substance abuse. The authors of this study examined the validity of a 2-question screening test for alcohol and other substances.

POPULATION STUDIED: The participants were 1252 patients randomly selected from 3 University of Wisconsin primary care clinics. They ranged in age from 18 to 59 years; 68% were women; and the population was racially diverse. Sixty-nine percent had private insurance. The prevalence of substance disorders in this study population was high (23%).

STUDY DESIGN AND VALIDITY: This prospective cohort study sought to identify 2 questions that could accurately screen for substance abuse. Screening questions were developed through a literature search and a series of focus groups. The interviewers asked patients the screening questions and then administered the Composite International Diagnostic Interview-Substance Abuse Module (CIDI-SAM), a series of questions based on the Diagnostic and Statistical Manual of Mental Disorders, third edition, revised used for identifying substance use disorders. The sensitivity of the screening questions was defined as the proportion of patients with a current substance abuse problem, as detected by CIDI-SAM, who had positive screening results. The high prevalence of substance abuse in this study will improve the positive predictive value of the screening test.This study was well designed and had a high response rate. Although the interviewers were not blinded while administering the screening questions and the CIDI-SAM, they were monitored closely, and a random subset of patients underwent urine drug testing. The authors also tested the validity of the screening questions with questions about patient comfort and truthfulness.

OUTCOMES MEASURED: The primary outcome measured was identification of either alcohol or drug abuse.

RESULTS: Among 1136 participants (91%), a positive response to either of 2 questions was 80% sensitive and specific for current alcohol or drug abuse. With the high prevalence of substance use in this sample, the positive predictive value of the 2 questions was 52% and the negative predictive value was 93%. Comfort with the interviewer was reported by 84% of the participants, and withholding any information by only 11%. Random urine substance screening of 231 patients revealed 14 positive test results in patients with a negative CIDI-SAM, but these results did not change the performance of the screening test.