I believe you have already seen this article but still,'Excluded, not dismissed: enhancing benefit in clinical research'. I think the diagnosis of underlying diseases in a volunteer is one of the benefits of the trial...whether he or she gets treated for the same is a different concern altogether

I have seen this article - thank you anyway. I was thinking more of a review on this subject...

Dear Jana,

Thank you for this really interesting question. Unfortunately, you'll find only few systematic studies on this topic. This is but also due to the research question. In general, clinical trials are even not carried out to discover so far unrecognized diseases. Except they are population-based prevention studies with a targeted screening for the discovery of certain diseases. We can well imagine that the interesting benefits that you mention, concern to patients, which are examined in a screening for a study on specific exclusion criteria. If then a certain disease is detected in such a screening, patients will be not included in the study and therefore they will not be observed furthermore, even if they are offered an appropriate treatment (which we want to suppose so). We know about it only when in a particularly interesting case, a doctor or investigator makes the effort to capture this in a case report and publishes it. Another way to tackle this problem is to conduct a literature review of epidemiological studies on specific diseases and to look, in how many patients a disease is firstly discovered by the screening due to study participation. I hope you still find some interesting answers to your question. Good luck.

That is an interesting issue, actually we came across it while screening postmenopausal women with CHD on manifest thyroid illness, and thus revealed a high incidence of subclinial thyroid dysfunction (which was in an exclusion criteria), but this has driven us to design a new study evaluating subclinical hypothyroidism.

Thank you all for sharing your experience.

I am preparing a case report on the subject - in one of our studies we found 1.5% of our patients have had a serious accompanying covert disease.

In consideration (and a bit of a joke): this would give participation in a clinical trial a NNT of 67, which is very good...

Finally a short note: Another approach would be to search for data on the estimated number of unreported cases for specific diseases and to examine the evidence for the estimation of the number of unreported cases.

In German we use also the term "Dunkelziffer" (engl. dark figure) in public health care. In the figurative sense "Dunkelziffer" refers to a disproportion of diagnosed (or even statistically recorded or reported) disease cases to actual disease frequency.