Skip to main content
. Author manuscript; available in PMC: 2012 May 16.
Published in final edited form as: Pharmacol Ther. 2009 Apr 8;123(1):1–16. doi: 10.1016/j.pharmthera.2009.03.011

Table 3.

Cessation and beyond: new indications and applications.

Indication or application Considerations for trial design Comment
Cessation Current 6 week abstinence model has served and probably should continue as basic model. This model has been used to justify limited time use, e.g., 6 months. Are longer trials or postmarketing surveillance needed to justify labeling for extended use?
Relapse prevention Could involve chronic and long term drug administration or acute use as needed to avoid relapse. Long term trials, e.g. 1–3 years, with large populations may be required. Innovative approaches include: (1) targeting populations at very high risk of relapse; (2) surveillance in users following restricted marketing approval as allowed in US FDA fast-track drug approval protocols. This could be an added indication to a medication approved for cessation but used differently or a new dose, formulation or entity, used analogously as “break through pain” (“rescue analgesics) for people with chronic pain who may or may not be maintained on a pain medication.
Maintenance of abstinence Generally conceived as long term chronic drug use. Long term trials, e.g. 1–3 years, with large populations may be required. Innovative approaches include: (1) targeting populations at very high risk of relapse; (2) surveillance in users following restricted marketing approval as allowed in US FDA fast-track drug approval protocols. This could be an added indication to a medication approved for cessation but used differently or a new dose, formulation or entity. For NRT and certain other approved medications with extensive use histories, long term safety concerns should not preclude such use.
Tobacco toxin exposure reduction Trials must demonstrate reduction with plausible health benefit if sustained without complete cessation but must support or at least not undermine eventual cessation. How the products are marketed and application of emerging risk minimization protocols may be vital to reducing unintended consequences such as undermining cessation.
Reduce to quit smoking Trials must demonstrate reduction with plausible health benefit if sustained without complete cessation but must demonstrate significant smoking cessation. Labeling and guidance would need to make clear that cessation was the ultimate goal. The concept would be to reach people for whom abrupt cessation is not achievable or acceptable.
Treatment of dependence on cigarette like products that are spreading in Western countries and common in SE Asia and India, e.g., clove cigarettes, bidis, kreteks. Dependence process appears similar to cigarettes for cigarette-like products with nicotine primarily inhaled at apparently comparable dose levels suggesting similar trial designs as for cigarette indications. It is possible that the major adaptation will be the supportive behavioral programs because patterns of use may differ somewhat.
Treatment of dependence on cigars and possibly waterpipes Some cigar smokers inhale but many absorb nicotine more gradually by holding smoke in the mouth and probably by holding the unlit cigar in the mouth. Nicotine dosing capacity of a single cigar can range from a few to more than 100 mg and patterns of use can range from several cigars per day to a few per week. Waterpipe smokers similarly can absorb large doses but typically in 1–3 sessions per day. Cigarette based trial designs will need to be adapted. As the dangers of cigar smoking are increasingly recognized there will be increasing pressures for at least dependent smokers to seek treatment, though this will probably not be appropriate for special occasion intermittent cigar smokers. Whereas waterpipe smoking was most common in the Middle East and Asia throughout the 20th century, the 21st century has witnessed rapid spread to the West, particularly in college campus settings suggesting increasingly concerns over the next decade or so.
Treatment of dependence on noncombusted oral tobacco products, e.g., snuff, chewing tobacco, and Swedish snus Nicotine delivery is slower onsetting than from inhaled smoke but doses can be very high, e.g., popular snuff brands in the US can deliver 10–20 mg per “dip” which is typically repeated 5–10 times/day. Cigarette based trial designs will need to be adapted. Seasonal use occurs with many athletes and it is not clear how trial designs would be adapted to such populations. The oral tobacco using population is increasing and will probably continue to do so as some smokers switch to such products, in part due to their marketing “for when you can’t smoke”. Although health risks are lower than for combusted products, the health risks are serious.