CardioExchange Archive

If we are to detect harms early and protect the public’s health while ensuring the availability of effective new therapies, systematic reporting of safety outcomes from all clinical trials must be available.

In the current Archives of Internal Medicine, Isabelle Pitrou and colleagues (FREE) review the reporting of safety data in randomized, controlled trials published during 2006 in the major journals. Their findings are disappointing but not unexpected. Adverse events were unreported in 11% of 133 articles. Most seriously, data on severe adverse events or adverse-event-prompted study withdrawal were missing in 27% and 47% of articles.

Editorialist John Ioannidis (subscription required) describes several missteps that lead to “insufficient or misleading” safety reporting:

the study design ignores or undervalues adverse events
adverse event information is not collected during the trial
reporting of adverse effects is distorted, restricted, or completely withheld

In my opinion, the issue is a question of priority. Word counts and page limits are tight, and investigators (and sponsors) focus on efficacy outcomes. Five or more tables and figures may be devoted to graphical display of efficacy, while a single table summarizes safety data. Because graphs are easier to skim, after a cursory look, the average reader takes away only efficacy data. Even the data that is presented is challenging to interpret — many trials (particularly those sponsored by industry) group adverse events by system, rather than as specific events.

One potential solution: Journals could require full and complete safety data, to be made available in on-line appendixes when necessary, allowing interested clinicians to weigh all safety information when making treatment decisions.

Safety outcomes must be prioritized to ensure high-quality patient care.

Other resources:
The 2007 FDA Amendments Act requires registration of all trials and reporting of primary and principal secondary (including safety) outcomes to http://clinicaltrials.gov — an online source of publicly available, easily searchable information that now includes 70,000 registered trials. With sufficient data quality, ClinicalTrials.gov could be the repository of safety information — ideally progressing to include raw data that allow independent re-analysis and meta-analysis.

So, do you pay attention to the safety outcomes when reading a clinical trial article? Have you ever looked specifically for the safety outcomes and not been able to find them? What did you do about it?

I am a creature of routine and order, and therefore don’t do very well with Southwest Airlines’ lack of seat assignment. Not so long ago, during a business trip to San Antonio, I was looking at my group C boarding pass and wondering if there would be any room for my carry-on luggage, or if I was going to have to sit in the last row of the airplane. As it turned out, both my fears became reality. Not the end of the world, but what came next was something I wasn’t prepared to handle.
The middle seat, or I should say, what was left of the middle seat, was the only one available. Two young, obese individuals each occupied about a fourth of my seat. I looked at the flight attendant who looked back at me, shrugging her shoulders and silently apologizing. I sat down and immediately felt my shoulders compressed; I literally could not move.
The plane took off. I knew I wasn’t going to be able to tolerate the feeling of confinement for the 4½-hour flight. I was already getting anxious, tachycardic, and I could feel my shirt drenched in sweat. The flight attendant saw my distressed face and asked me to stand with her at the back of the plane. She really prevented a panic attack. For almost the entire flight, I stood up in the back, chatting with the flight attendant. My row mates slept the entire time.
As a cardiovascular prevention specialist, I deal with obesity and counsel weight loss on a daily basis. But until that day, although I have always conceptualized obesity as a global epidemic, I was interacting with it as a one-person problem and not as an issue that can impact society in many ways. That day, my comfort and safety were jeopardized by the obesity problems of two individuals.
So my questions to you are the following: 

Should obese individuals be obligated to purchase two airplane seats instead of one?
Do you visualize obesity as a public health hazard, and, therefore, support a government role in implementing laws that might help halt the growing obesity epidemic? (e.g., regulating fast-food chains?)
As a physician, do you sometimes feel hesitant to bring up the obesity issue with your patients for fear of offending and consequently losing them? 

 
Editor’s note: Southwest Airlines’ articulation of their policy requiring the purchase of extra seats by customers of size addresses issues of individual sensitivity and public fairness.

The Framingham study has revolutionized our understanding of cardiovascular disease, but I wonder: is the 60-year-old study’s risk score getting a little long in the tooth?

Faced with the epidemic of heart disease and growing numbers of younger people worried about heart disease risk, I find that Framingham provides me little guidance.

As I see it, Framingham provides little insight for risk stratification in younger adults, and its 10 -year time horizon underestimates long-term cardiovascular risk and may give us a false sense of security. The FRS doesn’t work all that well in ethnically diverse populations or in those with lower socioeconomic status.

How many of you find the FRS helpful in determining a treatment plan for primary prevention? Do you follow the current guidelines and obtain an FRS for everyone? Do you have alternative approaches or risk scores that you use?