Abstract
A variety of new treatments for dementia are awaiting or undergoing randomized clinical trails. These trials focus on outcomes such as changes in cognitive function, physical function, or amyloid plaques. What is quite important and is too often missing from these trials are estimates of the impact of these treatments on the social and individual costs of providing care for those facing dementia. Until outcomes such as family caregiver time and caregiver burden are included in trails of dementia treatments, the picture of how well these treatments work will be distressingly incomplete.
Alzheimer's disease and the cognitive losses it involves are both frightening for individuals and terribly costly both for individuals and society. Almost 47 million persons worldwide currently live with dementia, and some suggest that number will grow to 131 million by 2050. Estimates of the worldwide costs of dementia in 2015 reached 818 billion US dollars. That figure may grow to one trillion dollars by 2030. These figures indicates that if Alzheimer's disease care were a country, it would have the 18th largest economy in the world. 1
It should be little surprise then that positive results from even small preliminary studies of treatments for dementia catch the interest of the pharmaceutical industry and the world of finance more generally. Each hint of an advance results in stories like Matthew Herper's article in Forbes in 2015 announcing that “Biogen Drug Could Inspire New Hope For Alzheimer's Treatments.” 2 Forbes was not alone; articles on the Biogen drug and similar medications awaiting or undergoing trials were highlighted in articles in The New York Times, Fortune, and Nature.3–5
As these articles suggest, excitement is growing in research and business circles about the potential for these new medications to change the trajectory of decline or symptom onset for mild Alzheimer's. However, such popular discussions, and research reports as well, invariably focus on the issue of statistically significant changes in tests of cognitive and physical function. 6 This latest round of research added the measurement of amyloid plaques in the brain as an important element of clinical trial outcomes. 7
These measures are, of course, tremendously important in understanding the dynamics and effects of these new medications on individuals facing Alzheimer's, especially when used by persons with prodromal or mild dementia. Unfortunately, this measurement approach in dementia treatment trials, with its emphasis on changes in cognitive and functional abilities, ignores important aspects of the challenges presented by dementia. These trials provide little, if any, information on the social and individual costs of caring for those with dementia.
The general social costs of dementia care reside overwhelmingly in the realm of the estimated cost of informal caregiving. It is important to note that the care usually referred to as “informal” care is almost invariably care provided by family members. In Zhu and her colleagues’ recent work, they found that 90.5% of “informal” care was provided by the spouse or children of the person with dementia. 8 As the Director of Duke University Medical Center's Alzheimer's Family Support Program argues, the connotation of the term “informal care” seems to imply something “casual or trivial,” while the reality of care at home for individuals facing dementia is anything but casual or trivial. It is a difficult, time-consuming, and often frustrating task that falls overwhelmingly to family members. Thus, what we often call “informal care” is better and more accurately referred to as “family caregiving.” (Lisa Gwyther, personal communication).
Estimates of the costs of care for those with dementia indicate that the social costs of the disease resulting from family caregiving literally dwarf care costs associated with formal care services (e.g., physician use, hospitalization, etc.). As Gustavsson and his colleagues indicate in their study of the costs of Alzheimer's care, “the potential cost savings for [dementia] treatment in an RCT sample is highest in informal [family] care.” 9
These general social costs of dementia care are obviously important, but it is also important to recognize that dementia carries individual costs not only for the person with dementia but for the person who is the primary family caregiver. Many of these costs are straightforwardly economic; other important costs are not. A more narrow focus on the individual costs of dementia caregiving, which are not directly economic, immediately moves us concern about a caregiver's subjective or perceived sense of burden. This burden is what Steve Zarit and his colleagues clearly defined three decades ago as “… an adverse effect on [the caregiver's] emotional, social, … physical, and spiritual functioning.” 10
Interestingly, in the available research on caregiver burden, one discovers that measures of cognitive function, which receive such weight in clinical trials of dementia treatments, have little effect on caregivers’ subjective sense of burden. The results of van der Lee and her colleagues’ systematic review of 56 studies of perceived caregiver burden were quite clear. These studies indicated that care recipients’ behavioral problems, mood disorders, and self-care needs dramatically and consistently affected subjective burden. However, a significant effect of cognitive function on subjective burden was rarely observed in these studies. 11
The available research identifies family caregiving as the major driver of the social costs of caring for those with dementia. In addition, the family caregiver's quality of life is dramatically affected by their subjective caregiver burden. Nonetheless, these individual and social costs are very often ignored in tests of dementia treatments. For example, information on Biogen's current Phase 3 trial of a seemingly promising treatment for dementia shows no indication of looking either at resource use or caregiver burden as an outcome. 12
Eli Lilly's relatively recently completed Phase 3 test of solanezumab involved resource use as a secondary outcome, though the effects of the medication on this outcome have not been reported. In addition, the trial included no data on caregiver burden. 13 Only in the much earlier trials of dementia treatments in the late 1990s and in the work of Gustavsson and his colleagues does one find a report on a treatment's effect on caregiver time and general social costs. 9,14 Disappointingly, even in these studies caregiver burden was ignored.
As early as 1995, Clipp and Moore argued that caregiver time should be an important outcome measure in clinical trial research on Alzheimer's disease. 15 What might have been a meaningful call to action was, with few exceptions, ignored. Over two decades later, it is again time to emphasize and remind pharmaceutical companies, and the researchers working for them as they attack dementia, of a truly fundamental reality in the real-world of dementia care.
Any trial of a medication intended to mitigate, delay, or erase dementia and its effects will fail to adequately assess that medication's effects if the trial does not include measures of the major social cost of dementia, family caregiver time, and information on a major individual “cost” of dementia, subjective family caregiver burden. Until these factors are regularly considered important outcomes in such trials, our picture of what effect these treatments have on this terrible and costly condition will be woefully inadequate.