Outcomes studies

The purpose of altering plasma lipoprotein levels is to reduce the risk of coronary events. The results of outcome trials are available for lovastatin (Downs et al, 1998), simvastatin (Scandinavian Simvastatin Survival Study Group 1994), and pravastatin (Shepherd et al, 1995 Sacks et al, 1996 The Long-Term Intervention With Pravastatin in Ischaemic Disease (LIPID) Study Group, 1998). Three of these trials, 4S, Cholesterol and Recurrent Events (CARE), and LIPID, studied patients with CHD, whereas the West of Scotland Coronary Revention Study Group and the Air Force Coronary Atherosclesosis Prevention Study (AFCAPS) evaluated the benefits of therapy in patients without known CHD. The main results of these trials are summarized in Tables la and lb. 

Risk Reductions Observed in Statin Megatrials in CHD Patients  

Despite the plethora of evidence provided by these trials and the publication of national guidelines (Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults 1993 Pyorala et al., 1994), many patients still go untreated, even those with CHD (Bowker et al., 1996 EUROASPIRE Study Group 1997 Pearson and Peters, 1997). Unfortunately, some practitioners are slow to change their clinical approach despite unequivocal results from clinical trials. 

As yet there are no completed megatrials with the newer statins. A study that compared atorvastatin versus angioplasty in 341 patients with stable CHD over 18 months was recently reported (Pitt et al., 1999). There were fewer ischemic events in the atorvastatin group, but the difference did not quite reach statistical significance. Furthermore, a previous study had shown a significantly lower incidence of such events in a group treated with conventional medical therapy, because angioplasty can be complicated by myocardial infarction and other acute coronary events (RITA-2 trial participants, 1997). 

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Tarlov A, Ware J, Jr., Greenfield S, et al. The Medical Outcomes Study. An application of methods for monitoring the results of medical care. JAMA 1989 262 925-30. 

Wojner-Alexandrov AW, Alexandrov AV, Rodriguez D, Persse D, Grotta JC. Houston Paramedic and Emergency Stroke Treatment and Outcomes Study (HoPSTO). Stroke. 2005 36 1512-1518. 

Antihypertensive drug name and dose is associated with compelling indications which are based on benefits from outcome studies or clinical guidelines. For example, the drug class aldosterone antagonists have eplerenone dosed at 25-50 mg per day which is indicated for heart failure patients after an Ml and supported by the EPHESUS trial. 

Cuijpers, Pirn, Annemieke van Straten, Gerhard Andersson and Patricia van Oppen, Psychotherapy for Depression in Adults A Meta-Analysis of Comparative Outcome Studies , Journal of Consulting Clinical Psychology 76, no. 6 (2008) 909-22... 

Friedmann PD, Lemon SC, Anderson BJ and Stein MD (2003). Predictors to follow-up health status in the drug treatment outcome study (DATOS). Drug and Alcohol Dependence, 69, 243-251. 

It is clear that the type 2 cytokines IL-4, IL-9 and IL-13 play an obligatory role in host resistance to nematode infection whereas type 1 responses promote host susceptibility. Therefore, given that susceptibility to nematode infection is not due to a lack of responsiveness perse, but rather the development of an inappropriate response, it is important to understand the factors that influence the induction and expansion of Th subset responses and so control infection outcome. Studies in nematode models and other systems have addressed these questions and identified the importance of host genetic factors, the nature of the antigen and the antigen presenting cell, co-stimulatory molecules on these cells, and the cytokine and chemokine environment immediately following induction of the response. 

The reasons that outcome studies in mutant mice may not necessarily translate to benefits for humans with ALS are discussed in a recent editorial [21]. 

Selection of drug therapy should follow the JNC 7 guidelines, but the treatment approach in some patient populations may be slightly different. In these situations, alternative agents may have unique properties that benefit a coexisting condition, but the data may not be based on evidence from outcome studies in hypertension. 

The Medical Outcomes Study 36-Item Short Form Health Survey and the Rhinoconjunctivitis Quality of Life Questionnaire measure not only improvement in symptoms but also parameters such as sleep quality, nonallergic symptoms (e.g., fatigue, poor concentration), emotions, and participation in a variety of activities. 

Therapeutic use (Phase III/IV) Refine understanding of benefit/risk relationship in general or special populations and/or environment Identity less common adverse reactions Refine dosing recommendation Comparative effectiveness studies Studies of mortality/morbidity outcomes Studies of additional endpoints Large simple trials Pharmacoeconomic studies... 

Naredi S, Olivecrona M, Lindgren C, Ostlund AL, Grande PO, et al. 2001. An outcome study of severe traumatic head injury using the lund therapy with low-dose prostacyclin. Acta Anaesthesiol Scand 45(4) 402-406. 

In recent years, there has been a growth in the field of mega-studies, usually clinical outcome studies involving 5000-25 000 patients, with a simple primary endpoint such as mortality and a number of secondary morbidity endpoints. The potential for studies of this magnitude to throw up less frequent side effects than those seen in the preregistration programme is clear. 

A large proportion of the technology appraisals so far performed by NICE on pharmaceuticals have been on products recently introduced into the marketplace. This has created difficulties for manufacturers trying to answer the questions posed by the appraisal. For most compounds, at the time of launch it is very unlikely that outcome studies will have been completed that allow accurate cost effectiveness calculations to be performed. The emphasis in Phase III is on clinical efficacy and safety to satisfy the requirements of the regulatory authorities. In most cases, it is impossible (and probably imethical) to perform pragmatic studies on the general population imtil safety and efficacy have been satisfactorily demonstrated in a tightly defined trial population. 

Although NICE is a UK (strictly England and Wales) institution, many countries already have or are establishing bodies that for evaluating the clinical effectiveness of new compounds. My comments on the need for outcome studies to potential changes to Phase III programmes and computer modelling are equally applicable in such countries. 

A recent review of studies published in the past decade (ADAA/NIMH, 1999) identified a total of 9 controlled and 15 uncontrolled psychosocial treatment outcome studies. In the last 2 years, at least four additional controlled treatment outcome studies for pediatric anxiety (excluding PTSD and OCD) have been published, and several large trials are underway. Although various psy-... 

Inadequate treatment duration is a rarely considered cause of TRD [Keller et al. 1982a, 1982b, 1982c]. In the context of TRD, a 4-to 6-week trial is inadequate to determine potential treatment efficacy. Most outcome studies have found only a 25%-30% remission rate by week 6 of treatment. Georgotas et... 

As might be suggested by the treatment outcome studies referred to above, anxiety disorders such as panic disorder have a chronic clinical course. A retrospective survey that reviewed literature on the course of depression and anxiety disorder before effective treatment became available [Keller and Baker 1992] showed that a high proportion of patients had little or no improvement in their condition over a number of years. Roughly half of 300 patients with panic disorder who received no active treatments showed no improvement over a 20-year period, for example. Like depression, panic dis-... 

Wells KB, Stewart A, Hays RD, et al The functioning and well-being of depressed patients results from the Medical Outcome Study. JAMA 262 914-919, 1989 Wells KB, Burnam A, Rogers W, et al The course of depression in adult outpatients. Results from the Medical Outcomes study. Arch Gen Psychiatry 49 788-801, 1992... 

Mojtabai, R., Nicholson, RA, Carpenter, B.N. Role of psychosocial treatments in management of schizophrenia a meta-analytic review of controlled outcome studies. Schizophr. Bull. 24. 569-587. 1998. 

Darke S, Ross J, Teesson M Lynskey M (2003). Health service utilization and benzodiazepine use among heroin users findings from the Australian Treatment Outcome Study... 

Teesson M, Ross J, Darke S, Lynskey M, Ali R, Ritter A Cooke R (2006). One year outcomes for heroin dependence findings from the Australian Treatment Outcome Study (ATOS). Drug and Alcohol Dependence, 83,174-80... 

We statistically summarize drug outcome studies, producing a bottom-line quantitative assessment of the difference between an experimental drug and placebo or other standard agent (see Drug Management later in this chapter). 

Wells KB, Katon W, Rogers B, et al. Use of minor tranquilizers and antidepressant medications by depressed outpatients results from the medical outcomes study. Am J Psychiatry 1994 151 694-700. 

Potosky AL, Knopf K, Clegg LX, Albertsen PC, Stanford JL, Hamilton AS, Gilliland FD, Eley JW, Stephenson RA, Hoffman RM. Quality-of-life outcomes after primary androgen deprivation therapy results from the Prostate Cancer Outcomes Study. J Clin Oncol 2001 19(17) 3750-7. 

Riley D, Fischer M, Singh B, Haidvogl M, Heger M. 2001. Homeopathy and conventional medicine an outcomes study comparing effectiveness in a primary care setting. J Alt Comp Med 7 149-159. 

Saper JR, Lake AE, 3rd, Cantrell DT, et al. Chronic daily headache prophylaxis with tizanidine a doubleblind, placebo-controlled, multicenter outcome study. Headache. 2002 42 470-482. 

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