UC San Francisco Authors Inadvertently Validate Our Call for Retraction

In the previous post I described fatal flaws in a study by University of California San Francisco’s Benjamin W. Chaffee, Shannon Lea Watkins and Stanton A. Glantz in the journal Pediatrics (here).  Their published response (here) validates my criticism.

Chaffee et al. correctly observed that I have frequently challenged flawed research, and they kindly provided three examples of my published letters to editors of scientific and medical journals.  My professional blog is replete with fact checks of published claims by federal officials (here, here, here, here, here, here) and government-funded researchers (here, here, here, here, here, here here, here) that e-cigarettes are a gateway to teen smoking.  My criticism has extended to research published by UCSF faculty (here, here, and here)

The recent Pediatrics analysis by Chaffee et al. showed that teen e-cigarette users in the Wave 1 FDA Population Assessment of Tobacco and Health (PATH) survey had higher odds of consuming 100+ cigarettes or past 30-day smoking one year later at follow-up.  I noted that the authors ignored important information about lifetime cigarette consumption (LCC), from as little as “1 puff but never a whole cigarette” all the way to having smoked 99 cigarettes.  When my research team applied LCC data to Dr. Chaffee’s analysis, his positive results for an e-cigarette “gateway” essentially disappeared. 

In response, Chaffee et al. called our addition of the LCC information a “statistical trick.”  By using that term, it appears that they believe, incorrectly, that the LCC variable is an outcome rather than a confounding factor.  Inexplicably, they described our analysis as “akin to suggesting that a study of hypertension should adjust for confounding by systolic blood pressure.” 

In this, Chaffee et al. prove our case. 

Let’s say we are studying the effect of dietary salt consumption on development of hypertension (systolic blood pressure, bp >140 mm) after one year of follow-up among participants who were not hypertensive at baseline (that is, they had a systolic bp = 90 to 139 mm).  If someone has a baseline bp of 139 mm, it is much more likely that they will have a bp of >140 mm after one year, compared to a person who had a baseline bp of 90.  It would be negligent to blame salt for causing hypertension while completely ignoring baseline systolic bp values in this example. 

The same principle applies to Dr. Chaffee’s e-cigarette study. 

The chart below clearly illustrates the large differences in LCC that Chaffee et al. ignored between never e-cigarette users and past 30 day users or triers.

It is negligent to ignore cigarette consumption at baseline while placing all the blame for smoking one year later on e-cigarette use. 

The Chafee article must be retracted.
 

Retract the UC San Francisco E-Cigarette “Gateway” Study

Some published articles are so flawed that they deserve retraction.   

A case in point is the Pediatrics article by University of California San Francisco's Benjamin W. Chaffee, Shannon Lea Watkins, and Stanton A. Glantz (here) that features a totally baseless claim: “Among adolescent cigarette experimenters, using e-cigarettes was positively and independently associated with progression to current established smoking.” 

Using Wave 1 of the FDA Population Assessment of Tobacco and Health (PATH) survey, Chaffee et al. define teen experimental smokers as having smoked “in your entire life” anywhere from “1 or more puffs but never a whole cigarette” up to 99 cigarettes.  They divide experimental smokers into three groups according to e-cigarette use: never users, past 30-day users and ever triers.  In their analysis, controlling for numerous variables, e-cigarette users at Wave 1 had higher odds of having consumed 100+ cigarettes or having smoked in the past 30 days at follow-up one year later.

The findings and the claim are false. In their analysis, the authors ignore the fact that their study group consisted entirely of experimental smokers with widely varied experience – one or more puffs but never a whole cigarette, one cigarette, 2-10, 11-20, 21-50 and 51-99 cigarettes. 

Using the PATH data, my research team reproduced Chaffee’s analysis and Pediatrics published our results online (here).  The table we submitted to the journal was published in an unreadable fashion, so we offer it here.

Odds Ratios (95% Confidence Interval) for Smoking Outcomes in the Wave 2 PATH Survey, According to E-Cigarette Use at Wave 1
Wave 2 Outcome (1 year)	Chaffee’s Results	BR-NP	BR-NP + Wave 1 LCC
Smoked 100+ Cigarettes
Never E-Cig	Referent	Referent	Referent
E-Cig Past 30 Days	2.56 (1.58 – 4.14)	2.60 (1.61 – 4.19)	1.21 (0.69 – 2.13)
E-Cig Trier	2.13 (1.43 – 3.18)	2.16 (1.46 – 3.22)	1.45 (0.88 – 2.38)
Smoked Past 30 Days
Never E-Cig	Referent	Referent	Referent
E-Cig Past 30 Days	2.29 (1.64 – 3.19)	2.12 (1.52 – 2.96)	1.41 (0.998 – 2.00)
E-Cig Trier	1.56 (1.15 – 2.12)	1.43 (1.05 – 1.95)	1.09 (0.78 – 1.52)
Smoked 100+ Cigarettes and Smoked Past 30 Days
Never E-Cig	Referent	Referent	Referent
E-Cig Past 30 Days	2.56 (1.52 – 4.32)	2.55 (1.51 – 4.31)	1.32 (0.75 – 2.30)
E-Cig Trier	2.41 (1.46 – 3.97)	2.45 (1.49 – 4.03)	1.70 (0.96 – 3.01)

BR-NP, Rodu-Plurphanswat reproduction of Chaffee et al. odds ratios
 

When we added lifetime cigarette consumption (LCC), the positive results for e-cigarettes essentially disappeared, negating Chaffee’s core claim.

 

It is well established that past smoking (in this case, LCC at Wave 1) predicts future smoking (one year later).  Chaffee, Watkins and Glantz ignored this information in order to claim that e-cigarettes are a gateway to smoking.  Their study should be retracted.  

I will review in my next post Chafee’s published response to our comment.

Instead of Greenlighting IQOS Sales, FDA Continues to Slow-Walk Safer Cigarette Substitutes

The introduction of heat-not-burn cigarette substitutes in Japan has led to a precipitous reduction in cigarette consumption.  

Tobacco industry analyst Michael Livery of Piper Jaffray recently issued a report on the Japanese market, citing 2017 sales data. The chart at left suggests that Philip Morris International’s IQOS heat sticks (green) and BAT’s Glo products (blue) caused a 13% decline in cigarette consumption for the year.  Livery deliberately underestimated the number of heat sticks sold because of evidence that up “to 20% (4^th Quarter 2017) of iQOS HeatStick volumes…is getting re-sold in China, Thailand, and Hong Kong, and likely other parts of Asia.”

I suggested (here) that a similar result could be possible in the U.S., if the FDA grants marketing approval for such products. The agency, however, appears to be in no rush to make a decision.

Philip Morris submitted a premarket tobacco application (PMTA) to the FDA on March 31, 2017; it has been pending ever since.

According to the FDA (here), if a PMTA is accepted and found to be complete, the agency will file it and begin substantive review.  “After completing its review, FDA intends to issue an order within 180 days after receipt of the Premarket Tobacco Application that the new product may or may not be introduced or delivered for introduction to consumers.” (emphasis added)

The FDA took eight months to grant Swedish Match a PMTA for eight snus products in 2015 (here).  This week marks the twelfth month of FDA consideration of the IQOS PMTA submitted March 31, 2017.

It is often said that regulation is a slow, deliberate process.  But in this instance the FDA is in apparent violation of its own procedural guidelines.  The FDA simply slow walks any decision on safer options for smokers: it took 2.5 years (here) and 4 years (here) to reject requests to correct inaccurate smokeless tobacco warnings.  All of these are examples of regulatory purgatory that I warned about six years ago (here). 

Our country’s smokers and their loved ones deserve better.