Spin in writing-6: A critic of a case-control study

This post is a follow-up to my previous post on the same topic, which was inspired by a journal club podcast that dealt with a research paper on Cannabis use and psychosis.

The podcast was presented by Matt. Chris, and Don at the Population Health Exchange of the Boston University School Health Public Health.

Delving into the subject, in this post, I am deconstructing the paper with an emphasis on “spin in science writing”.

About the study

This was a case-control study conducted in several countries. It appeared in The Lancet Psychiatry in 2019. Its title is “the contribution of cannabis use to variation in the incidence of psychotic disorder across Europe (EU-GEI): “A multicenter case-control study”: You can access the full paper by clicking this link.

About the study design

In the abstract’s methods section, the authors write: “We included patients aged 18–64 years who presented to psychiatric services in 11 sites across Europe and Brazil with first-episode psychosis and recruited controls representative of the local populations.”

My comment: The cases were the first-episode psychosis. They are the ideal choice to explore incident (new) cases. However, another research reveals that the median time between the first appearing of symptoms and the diagnosis of first-episode psychosis is 2-2.5 years and the median age at diagnosis is 30 years in the UK. Further research reveals that as many as 64 percent who first experienced the first-episode psychosis have used cannabis and 30 percent of them had a cannabis use disorder. These facts resonate with one of the inherent problems in the retrospective case-control design: The problem of recall bias. It is troubling because the relationship between cannabis use and first-episode psychosis could be bi-directional.

Moreover, as the journal club podcast presenters point out cannabis may be just unmasking psychosis among those who are genetically predisposed.

Because of these reasons, the temporality – whether cannabis use precedes the first-episode psychosis – is very difficult to adduce.

Causality assumption:

In the abstract’s methods section, the authors write: “Assuming causality, we calculated the population attributable fractions (PAFs) for the patterns of cannabis use associated with the highest odds of psychosis and the correlation between such patterns and the incidence rates for psychotic disorder across the study sites.”

Assuming causality: The authors “assume causality” in their study based on findings from previous studies. As podcast presenters highlight, this assumption is a huge part because case-control study design, by definition, does not allow a causality assumption. After assuming causality, they have gone further and calculated population attribution fraction (PAF).

Causality language cannot be used in case-control study designs.

Causality language

Case-control study designs are observational by nature. They allow us to conclude associations, certainly not causations. In other words, we cannot use words or phrases that allude to causality; which means no declarative verbs. Instead, we should ideally use “descriptive” verbs to describe associations.

You can find more details about what declarative and descriptive verbs mean by reading this post.

In this post, I search and highlight the sections, sentences, and phrases that I consider containing declarative and descriptive words and verbs.

However, I request readers to contribute to this post and am willing to correct myself if my facts and arguments are incorrect as per your opinion.

In the study’s title:

The authors write: “The contribution of cannabis use to variation in the incidence of psychotic disorder across Europe (EU-GEI): a multicenter case-control study”.

My comment: Case-control study designs may prove association but not causation. The phrase – “contribution” of cannabis use to the “incidence” of psychotic disorder – alludes to a causative relationship. However, the word, “contribution” may mean an association also.

In the abstract:

Findings section: The authors write: “Daily cannabis use was associated with increased odds of the psychotic disorder compared with never users (adjusted odds ratio [OR] 3·2, 95% CI 2·2–4·1)”.

My comment: This is a correct characterization of the study findings because the case-control study designs warrant using the phrase, “associated with”.

Prevention?:

Findings section: The authors write: “The PAFs calculated indicated that if high-potency cannabis were no longer available, 12·2% (95% CI 3·0–16·1) of cases of first-episode psychosis could be prevented across the 11 sites, rising to 30·3% (15·2–40·0) in London and 50·3% (27·4–66·0) in Amsterdam.”

My comment: They claim that by removing high-potency cannabis in these 11 sites 12.2 percent of cases of first-episode psychosis could be prevented. And, in some sites – London and Amsterdam – it could be as much as 30.3 percent and 50.3 percent. This claim goes way beyond the study design warrants because it is based on causality.

Interpretation section: The authors write: “Differences in frequency of daily cannabis use and in use of high-potency cannabis contributed to the striking variation in the incidence of psychotic disorder across the 11 studied sites. Given the increasing availability of high-potency cannabis, this has important implications for public health.”

My comment: Is it possible to use the phrase, “contributed to the incidence of psychotic disorder” because it alludes to, again the causality?

In the main text:

Results section: The authors write: “The use of high-potency cannabis (THC ≥10%) modestly increased the odds of a psychotic disorder compared with never use.”

My comment: In this sentence, the use of the word, “increased” suggests causality.

The authors write: “Adjusted logistic regression indicated that daily use of high-potency cannabis carried more than a four-times increase in the risk of a psychotic disorder (OR 4·8, 95% CI 2·5–6·3) compared with never having used cannabis.”

My comment: The phrase: ” four-times increase in the risk of psychotic disorder” suggests causality.

Discussion section: The authors write: “The strongest independent predictors of whether any given individual would have a psychotic disorder or not were daily use of cannabis and use of high-potency cannabis.”

My comment: The word, “predictor” suggests causality.

The authors write: “The odds of the psychotic disorder among daily cannabis users were 3·2 times higher than for never users.”

My comment: I believe that this is a correct characterization of the findings.

The main focus of this post is to highlight reporting practices of a case-control study with special reference to the causality language. However, there are several other areas that we can discuss here; one such issue is the recruitment of controls and their comparability.

The problem of recruiting controls:

Ideally, the recruited controls should be “potential cases”. In other words, should they experience first-episode psychosis, they are expected to be included in the study as cases. Therefore, both groups’ basic characteristics should be more or less similar. However, according to Table 1, we find statistically significant differences between cases and controls in age, ethnicity, education status; the cases were younger, lower educational status, and non-whites. That means the control group did not represent the local population from where the potential cases of first-episode psychosis should originate.

I found another excellent account based on this paper written by Suzanne H. Gage to The Lancet. It also enriches this discussion. And, I found another excellent write-up by Kristen Monaco written to MedPage TODAY.

Author: Prasantha De Silva

A specialist in Community Medicine board-certified in Sri Lanka and a research analyst in Canada

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