Table 4.

Special populations.

Indication or application	Considerations for trial design	Comment
Pediatric indications	Youth develop dependence and withdrawal with 50% trying to quit and most regretting having started before age 18, however, patterns of use and behavioral and social factors may require adaptations of clinical trial designs used for adults.	The safety benefit ratio will be an important consideration due to the fact that one third or more youth in some countries (e.g., the US) discontinue smoking in early adulthood without treatment.
Pregnant women	Outcomes may include neonatal weight, pregnancy complications.	Safety concerns exist but have been partially addressed through labeling of current medications and extensive real world experience.
Cancer patients	Trials may need to focus as much on quality of life as cessation. Treatment and disease-related outcomes may be cancer organ site and trial specific.	Safety concerns including effects on cancer prognosis might be preliminarily addressed with biomarkers but resolution may require post-marketing studies.
Respiratory disease	Trials may need to focus on potential indirect respiratory benefits and quality of life.	Safety concerns including effects on lung disease prognosis might be preliminarily addressed with biomarkers but resolution may require post-marketing studies.
Heart disease patients	Major premarketing outcomes may be the absence of exacerbation of heart disease.	Safety concerns including effects on heart disease prognosis might be preliminarily addressed with biomarkers but resolution may require post-marketing studies.
People with psychiatric co-morbidities, e.g. depression, schizophrenia, anxiety	Trials will need to minimize risk of adverse impact of other psychiatric disease and treatment and presumably need to demonstrate no adverse impact and/or how to minimize adverse impact.	It is likely that although psychiatric co-morbidities are grouped in this table that approaches will vary across condition and indications may be condition specific (e.g., for patients with depression).
People with other drug dependence disorders	Trials will need to minimize risk of adverse impact of other psychiatric disease and treatment and presumably need to demonstrate no adverse impact and/or how to minimize adverse impact.	It is likely that although drug dependence disorders are grouped in this table that approaches will vary across condition and indications may be condition specific (e.g., for patients with alcohol dependence).