Long-term Follow-up of the TIPS early detection in psychosis study: Effects on 10-year outcome – facilitated by Dr Andrew Amos

References

Hegelstad WtV,  Larsen TK, Auestad B, Evensen J, Haahr U, et al. Long-term Follow-up of the TIPS early detection in psychosis study: Effects on 10-year outcome. American Journal of Psychiatry 2012; 169(4):374-380.

Article Summary

Hegelstad and colleagues (2012) report the 10-year follow-up results of an experiment which compared psychotic symptoms, remission/recovery rates, and functional indicators between two geographic locations. One area was subjected to a public health intervention intended to reduce the duration of untreated psychosis (DUP) – the early detection area (ED), while the other location left normal detection procedures in place (no-ED). It was suggested that there were no relevant differences in the treatment received or populations covered at each location. The public health intervention included advertising; outreach to schools and primary care doctors to educate the public about warning signs of psychotic illness; and early detection teams who would rapidly attend people identified as possibly having a psychotic illness.

The original study was constructed in response to an established association between longer DUP and worse outcomes in psychotic illness. The quasi-experimental design was intended to test the hypothesis that a longer DUP causes a worse outcome. An alternative hypothesis is that an insidious onset of psychotic illness is associated both with a longer DUP due to the absence of prominent hallucinations/delusions, and with a worse outcome, as negative symptoms are less responsive to treatment.  DUP was 16 weeks in the no-ED area, and 5 weeks in the ED area.

Hegelstad and colleagues’ report of data appears to engage in the processes of selective reporting bias and spin as defined by Vera-Badillo et al (2013; journal club article 13/02/13).

  • At 10 year follow-up, all the clinical and functional measures of the original study are not significantly different (and one measure is worse for the treatment group). Despite this, the authors claim in the abstract to have demonstrated that earlier detection of psychosis has reduced deficits and improved function. They base this conclusion on a completely new measure called “recovery”, which was not considered at baseline, 1 year, or 5-year follow-up, and which appears to be a proxy for vocational outcome, itself not significantly different at five-year follow-up.
  • They do not examine the original hypothesis, that longer DUP causes a worse outcome, despite reporting a logistic regression which demonstrates no association between DUP and outcomes.
  • They do not consider the alternative hypothesis, which emerged spontaneously before it was presented, that the intense effort to identify patients with psychosis might also sample selectively and recruit a less affected group of people.
  • They do not report hospitalisation, despite this measure being significantly worse for ED patients at five-year follow-up (suggesting early detection actually caused a worse outcome)
  • They discuss only the putatively better outcome of recovery in the ED group, without discussing the relatively worse outcome in independent living for the ED group
  • They suggest that the non-significant results may be due to the selective attrition of relatively higher-functioning patients from the ED group, but do not discuss the fact that there was a selective attrition of patients with longer DUP from the ED group, and not from the no-ED group. If longer DUP is a causal mechanism, this would improve the measured outcomes of the ED patients.

Discussion

Discussion included references to other literature particularly prone to the use of spin and bias. The support of pharmaceutical companies in the disclosure statement was noted, and potential advantages for pharmaceutical companies were explored. An analogy was suggested between criticisms of over-prescription of stimulant medication in ADHD and potential over-prescription of antipsychotic medication or other interventions for people with psychotic illness, psychotic experiences, or general distress at the same time as psychotic symptoms.

It was noted that schizophrenia has a prevalence of around 1% in most epidemiological studies, while subclinical psychotic experiences are believed to occur in up to 8-10% of the population (with higher rates in younger people). It was speculated that the intense effort to identify patients with psychotic illness might lower the threshold for entry into care, and that once antipsychotic medication was in place, it might be maintained for years as prophylaxis despite no definitive psychotic illness ever emerging.

It was also discussed that while the Vera-Badillo paper examined the proportion of spin/bias in more than 150 RCTs, Hegelstad et al (2012) reports the only methodological adequate study in this area. Spin/bias therefore was suggested to be especially damaging, as there is no counterweight to provide context.

Finally, the extension of the spin/bias analysis to the more general early psychosis literature was floated. The possibility of widespread spin/bias was suggested by a quote from a prominent early intervention advocate:

  • “In psychiatric as well as other reform processes, logic and scientific evidence are necessary but insufficient. Rhetoric, marketing, effective networking, altruistic promotion of a vital public health issue, economic arguments, and a confluence of common interests have fuelled the momentum and are vital for real reform to take root.” – McGorry (2005; p.s2)