most treatment studies are done with a very specific purpose in mind : to gain approval or acceptance of a particular therapeutic modality .
research following the regulatory model is specifically geared to the legal requirements of drug approval and registration .
although there is no equivalent to the food and drug administration ( fda ) for psychotherapy , the methodology of the regulatory model has been adopted in that field as well . in order to establish efficacy ,
this has led to the practice of eliminating from clinical trials all patients with comorbid illnesses , coexisting conditions , and even potentially compromising psychosocial or environmental characteristics .
observation periods are , typically , very short . in order to prevent administrative or delivery problems from masking the effect of the treatment
intrusions such as the administrative requirements of a health care plan or third party payer are minimized , and the treatment is provided in optimal form , often in an academic health center .
specific measures are taken to ensure compliance of the clinician with the protocol and adherence of the patient with the procedures and treatments .
formally , efficacy studies define optimal treatment outcomes for narrowly selected patients treated under rigidly controlled and ideal conditions . with a primary focus on symptoms , the assessment of efficacy
is based upon the degree to which the level of symptomatology is reduced or eliminated . in an efficacy trial , treatment is provided by specially selected and trained clinicians who provide optimal treatment and expend substantial resources to ensure compliance and minimize drop out .
research supported for commercial purposes , particularly that supported by the drug companies themselves , has , of necessity , conformed to the regulatory model .
this is the case regardless of whether the site of the study is an academic health center or a community- treatment facility , and regardless of whether the coordination of the study is done directly by the sponsor or by an intermediary ( contract research organization , or cro ) .
it is worth noting that those doing clinical psychotherapeutic or behavioral research have not ( yet ) adopted this cro type of arrangement .
the regulator)- model has also been carried over into research that has no industrial sponsorship , even to research on mental disorders that has been directed to government agencies or foundations . in a treatment study driven by a regulatory model of investigation , there is no minimum effect size or minimum pro portion of rcsponders necessary . in addition
, there is no requirement that the subject population be representative of the kind of patient seen in actual practice . as such , a trial done in accordance with the regulatory model represents only the beginning of a process of clinical development .
efficacy studies define optimal treatment outcomes for narrowly selected patients treated under rigidly controlled and ideal conditions .
the classic efficacy trial is used to define the gold standard of the best outcome under ideal circumstances . because of the tight standard of control required in efficacy studies , the policy and practice relevance of these trials will always be limited . 
 
the clinical trials of cognitive enhancers provide a useful example of the differences between regulatory and public health research .
the trials of cognitive enhancers seek to show slowing or reversal of the progression of alzheimer 's disease or to demonstrate improved management of the symptoms of the disease .
these trials typically attempt to show that the course of a progressive disease has been modified .
the design of such trials involves great complexities even under optimal conditions . in an effort to demonstrate efficacy within the regulatory model , current clinical trials involving
antidementia compounds typically exclude any patient with psychiatric or neurologic symptoms or substance abuse , and require the patient to be generally physically healthy and living with a caregiver .
schneider et al applied these criteria to a large , state -wide database in california and excluded all but 10% of patients .
the resulting sample was younger , less severely ill , more highly educated , and more likely to be white and with higher incomes than the population as a whole .
these sorts of data provide little guidance to the patient , family , or clinician in the selection of treatment approaches .
in fact , there is a small but growing literature on issues relating to subject selection in clinical trials . in schizophrenia , for example , subjects tend to be younger than the general clinical population and are more likely to be male and part of an ethnic minority . in the treatment strategies in schizophrenia ( tss )
study , fewer than 10% of those screened were actually enrolled in the study the story is much the same in bipolar illness . in general , subjects enrolled in studies tend to have been ill for a very long time - 15 years in bipolar trials - and are unstable or unsatisfied with their current treatment . even in studies attempting to recruit first - episode patients , the period of undetected or untreated illness exceeds 3 years . 
 
age itself is a common concern , with many studies having an arbitrary age cutoff of 55 or 60 years . even 
geriatric  studies have been restricted , for all intents and purposes , to the  young - old  population of patients in their sixties .
few older patients have ever been studied , despite the clear impact of advanced age on pharmacokinetics , dynamics , and drug metabolism and on treatment response .
in general , the rigid exclusions of most regulatory - oriented clinical trials have significantly distorted the conclusions of these studies .
studies that are informed by a public health model are often , called  effectiveness  studies .
we avoid use of that term , since it seems to convey multiple and conflicting meanings in different audiences .
public health studies bring us into the world of actual practice with time - pressured clinicians taking care of large numbers of patients with uncertain clinical presentations , complex comorbidities , and varying degrees of interference with ideal levels of compliance .
the exclusive focus on symptomatology is expanded to include outcomes related to issues of function , disability , morbidity , mortality , resource use , and quality of life .
the classic public health trial is used to assess the expected outcome under usual circumstances of practice . 
 
in contrast to the elegantly crafted efficacy trial , a public health trial must be bigger in size , simpler in design , broader in terms of inclusions and narrower in terms of exclusions , and more representative with respect to settings of care .
these settings will not be limited to academic health centers or tertiary care institutions , but will include primary care , community settings , and long - term care institutions . unlike efficacy trials , where specially trained clinicians carry out state - of - the - art assessment and treatment , public health trials are carried out in settings of usual practice where there is a broad and variable range of clinician expertise and experience with the disorder under study .
outcome measures will necessarily extend beyond symptomatology to include function , disability , morbidity , mortality , health care and other resource use , family burden , institutionalization , and quality of life .
public health studies are not simply secondary analyses of administrative data collected in large and naturalistic databases , but are treatment trials that are broadly representative of clinical , family , and organizational factors . 

we begin with the assumption that the mental disorders of late life are chronic , recurring conditions . within this broad perspective , three types of studies would seem to be appropriate .
first arc treatment trials including both short - term and long - term studies directed toward management of symptoms , optimization of function , and minimization of disability .
the methodology of these trials is well established and accepted by all those involved in clinical care .
however , the conceptualization of the nature of treatment response is broader in public health trials than in regulatory trials . rather than focusing exclusively on response as a dichotomous variable , ie , responder or nonresponder
, a public health approach requires in addition that attention be paid to speed of response , completeness of response , and durability of response .
an intervention directed at the speed of response fits within an overall conceptualization of treatment .
the question is how can we accelerate the response to treatment and how early in the treatment process can we know when an approach to treatment is likely to fail ? a related question concerns the management of treatment - resistant cases .
regardless of how treatment response is defined , we know that invariably a subset of patients show incomplete responses or nonresponse to any given treatment intervention . under the regulatory model , the management of nonresponders and partial responders receives relatively little attention .
yet treatment - resistant patients make up a significant portion of actual clinical practice and they account for a major share of the mortality , morbidity , and cost of mental illness .
therefore , a public health orientation requires that the management of treatment resistance be a priority for investigation .
an intervention directed at the completeness of response is considered rehabilitative . the question is how well is well and can we improve the nature of response by targeting interventions to reduce residual symptomatology posttreatment ?
a rehabilitative strategy might entail augmentation with a new pharmacologic or psychotherapeutic agent or some significant alteration in lifestyles and circumstance .
the question is once well , how can we stay well and can we reduce the risk of relapse ( of the same episode ) or recurrence ( of a new episode ) through some longer term approaches to treatment ?
interventions are also preventive if they target the excessive levels of disability that often characterize the mental disorders of older people . as we learn more about the risk factors , etiology , and pathophysiology of mental disorders in late life , it is conceivable that preventive interventions could be directed toward delaying the onset of disease or even preventing the onset entirely . 

in order to carry out such studies , whether they are treatment studies , preventive interventions , or rehabilitative interventions , we need to identify the structural barriers in the ways in which research is organized and to innovate approaches to address these barriers .
the role of the academic health center is being redefined in the context of health care system reorganization , and access to patients has become problematic .
patient - oriented research is seen as a particularly fragile enterprise at this point in time . 
 
many academic health centers are part of clinical systems that include community hospitals , primary care and specialty care office practices , and capitated contracts .
the nonacademic settings of these large networks are where the majority of patients are located .
the new challenge for the field is how to turn these clinical and administrative networks into research networks for the development and management of intervention trials . at the same time , the parallel challenge is how to identify the critical elements of academically based protocols and paradigms , and adapt them for use in the broader community .
advancement for academic investigators is based on research productivity , usually measured by significant publications and success in developing extramural funding .
large - scale , longitudinal , public - health - oriented studies typically have a very long period of time before important publications are developed , and they usually involve the participation of a large number of investigators .
if there is a commitment to developing this type of research , the challenge for the field is how to adapt promotion and tenure policies to this situation so as to properly recognize individual contributions .
similarly , much of the training of new investigators is based upon a model of individual scientific activity : the independent investigator directing a small group of junior colleagues , fellows , students , and technicians .
training typically does not prepare investigators for participation in large - scale endeavors . nor are there established training pathways into some of the newer roles in large - scale studies , database management , clinical coordination , site management , etc .
determination of priorities within this broad panorama of intervention research is always the result of the complex interaction between public health need and scientific opportunity .
death , disability , and societal and family burden have each been proposed as the sole criterion for policy determination . for example , in the influential text the global burden of disease , major depression , bipolar disorder , schizophrenia , and obsessive compulsive disorder are all included on the list of the 10 leading causes of disability worldwide . in fact , major depression is identified as the leading cause of disability . on the other hand , in that same study , no mental disorder
the identification of significant areas of scientific opportunity is equally problematic , with investigators from different fields advocating on behalf of substantial increases in the investment in their particular areas of interest .
the national advisory mental health council , with the legislative mandate to guide policy development and program support , has become a valuable sounding board for the identification of promising scientific opportunities .
this council has produced recent reports on genetics research , prevention research , and the interface of clinical trials and mental health services research . 
 
priority setting must be part of a continuing process of programmatic adjustment , readjustment , and redirection in the field .
new treatments must be developed as our knowledge base of basic and clinical neuroscience and behavioral science expands .
established treatment approaches must be fine - tuned in accordance with the needs of patient populations and the settings in which they receive care .
research must catch up with practice and evaluate the many common approaches to treatment that have developed without a firm base of research . here
we include such approaches as continuation and maintenance electroconvulsive therapy- , reduction or taper strategies , treatment algorithms or decision trees for patients with treatment refractory illness , and unusual treatments such as mcthylphenidatc for minor depression .
a wealth of potentially promising treatment approaches currently exists in the form of case reports , uncontrolled studies , letters to the editor , and internet postings . a major goal for the public health enterprise will be to organize and systematically study these interventions and identify those which are clinically valuable and those which are not . as part of a public health mission , we must also attend to issues of safety and consumer protection .
for example , the widespread use of over - the - counter , unregulated treatments needs to be carefully examined for possible benefit and for potential harm .
use of complementary and alternative approaches is very high . even in patients volunteering for participation in clinical drug trials , use of herbal medications
is substantial ; in a series of 150 such subjects , emmanuel and colleagues report that 56% have used herbs in the last month .
it is therefore incumbent upon us to evaluate these treatments , including natural products such as st john 's wort or kava , psychophysiologic approaches such as eye movement desensitization and reprocessing ( emdr ) , and somatic approaches such as acupuncture , if for no other reason than that our patients are using these in large , uncontrolled , natural experiments
our patients are not helped by treatments that are available in only in scientific journals .
lehman and steinwachs report that fewer than half the patients with schizophrenia in the united states received a level of care that was consistent with the current state of the art .
this is an important finding that can not be ignored . as a field we must take on the challenge of translating our research into practice and placing the most powerful clinical tools in the hands of patients , their families , and the clinicians that care of them
the mental health field is significantly altering the culture of treatment research by moving from a narrowly defined regulatory model to a more inclusive public health model . this new approach to intervention promises to improve patient care by addressing the types of practical questions and functional outcomes that are typically brought to the attention of clinicians .
this new generation of research is directed toward defining standards of appropriate and cost - effective treatment for the diverse population of patients seen in all health care settings .
this should not be taken to indicate that there is no place for the highly controlled efficacy research needed to establish that a treatment has merit .
but rather it is now the case that efficacy is the beginning of a process of inquiry and not the end .
the interdependence of challenge and opportunity , often used as a clich , should be considered real and entirely appropriate in this instance .
the challenge to all of us as patients , clinicians , scientists , or educators is great .
, there is a wonderful opportunity to have a significant impact on improving patient care .
 the mental health field is transforming the culture of treatment research by moving from a narrow regulatory model geared to drug approval and registration to a more inclusive public health model . 
 thus , whereas regulatory antidementia trials will exclude patients with psychiatric or neurologic symptoms or substance abuse and require them to be physically healthy and living with a caregiver , ie , 90% of the presenting alzheimer population , the public health model promises to improve patient care by addressing the types of practical questions and functional outcomes typically the concern of clinicians : does treatment enhance function ? 
 how can we keep people well once they have been made well ? 
 why do treatments not work as well in practice as in clinical trials ? 
 public health studies are conducted in the world of actual practice with time - pressured clinicians taking care of large numbers of patients with uncertain clinical presentations , complex comorbidities , and varying degrees of interference with ideal levels of compliance . the exclusive focus on symptoms 
 is expanded to include outcomes related to issues of function , disability , morbidity , mortality , resource use , and quality of life . 
 highly controlled efficacy research is still needed to establish treatment merit , but efficacy now marks only the beginning of the process of inquiry . 