The exclusion of older subjects from clinical trials: the PREDICT study
Antonio Cherubini1 & Peter Crome2
1IRCCS‐INRCA, Ancona, Italy
2University College London, London, UK
Introduction
Clinical trials are considered the gold standard methodology to demonstrate the efficacy and safety of an intervention, whether it is a drug, a non‐pharmacological treatment, or a multicomponent intervention. Although Avicenna, an eleventh‐century philosopher and physician, in his book The Canon of Medicine, wrote the rules for experimental testing of drugs, the first true example of a clinical trial can be considered to be the experiment performed by James Lind in 1747. This scientist gave different acidic substances to sailors suffering from scurvy and found that those who ate oranges and lemons recovered from the disease after a few days. Nevertheless, the science of clinical trials is relatively young. The first example of a randomized trial is a study evaluating the effect of streptomycin in patients with tuberculosis, that was published in 1948 in the British Medical Journal [1]. In the past sixty years, clinical trial science has rapidly evolved in its theoretical and practical aspects [2]. However, clinical trials have developed following the dominant medical paradigm known as the “disease model” [3]. This implies that they are usually aimed at treating a specific disease with a specific treatment, avoiding, as much as possible, all the confounding factors that might interfere with the assessment of the efficacy and safety of the tested intervention. Therefore, clinical trials establish strict inclusion and exclusion criteria that select patients suffering only from the disease of interest and in need of no other treatment than that tested in the trial. However, these selection criteria tend to reduce the number of patients who are eligible to such an extent that those included are usually not representative of the patients who will be treated in clinical practice. This discrepancy between the trial population and the real‐world
Clinical Trials in Older Adults, First Edition. Edited by Antonio Cherubini, Roberto Bernabei, Luigi Ferrucci, Niccolò Marchionni, Stephanie Studenski, and Bruno Vellas.
© 2015 John Wiley & Sons, Ltd. Published 2015 by John Wiley & Sons, Ltd.
population is widening as the aging of the population is accompanied by a higher prevalence of multimorbidity and, as a consequence, of multiple treatments, both with drugs and with non‐pharmacological interventions (see Chapter 4). The results obtained in the context of the clinical trial often cannot be applied to the real‐world patient population but only to a minority of subjects. In other words, the generalizability of trial results is decreasing and hence also the usefulness of the results to clinical practice. Older subjects, as well as children, are one of the most important categories that have suffered from this approach, often being excluded from clinical trials [4–6].
The elderly are the fastest‐growing section of the population in almost every country in the world. Since most long‐term conditions increase in prevalence with age, and older people take more medications than other groups, their exclusion from clinical trials has caused increasing concern. The efficacy, as well as the safety, of pharmacological and non‐pharmacological treatments are often not well established in older patients. There is a risk that the evidence obtained in younger subjects if applied directly to older patients might not always be appropriate and in line with good clinical practice [7]. On the other hand, this situation may persuade some practitioners to avoid useful treatments in these subjects, leading to under‐treatment, which is quite prevalent in the older population [8].
The PREDICT (Increasing the Participation of Elderly in Clinical Trials) study was funded by the European Union (EU) Seventh Framework program in 2008 with the aim of helping identify, address, and resolve the issues related to the exclusion of older people from clinical trials. This chapter will present and discuss the rationale and the most important findings of this project.
the exclusion of older people from clinical trials: a long‐term issue
In the past twenty years, several studies have reported that older patients are under‐represented in clinical trials that evaluate not only drug but also non‐drug treatments for different conditions [9]. One of the first studies that highlighted this issue was undertaken by Gurwitz at the beginning of the 1990s [10]. The premise was that an increasing proportion of patients admitted to US hospitals with acute myocardial infarction were older subjects, while the patients included in clinical trials were significantly younger and more often men than women. The authors investigated the extent to which the elderly were excluded from trials of drug therapies used in the treatment of acute myocardial infarction performed before September 1991. They found that over 60% of trials excluded persons over the age of 75 years. Moreover, studies published after 1980 were more likely to have age‐based exclusions compared with studies published before 1980. Finally, studies with age‐based exclusions had a smaller percentage of women compared with those without such exclusions. Since the majority of
older subjects are women, this results in an even more pronounced limitation of the number of female older patients included in clinical research. A decade later, Lee and colleagues performed a new evaluation of clinical trials in acute coronary syndromes [11]. The authors conducted a thorough literature search of Medline and the Cochrane Database of Systematic Reviews from their beginning up to the year 2000. The included 593 unique cardiovascular randomized controlled trials (RCTs). The majority were multicenter and undertaken in a single country. Industry was the most commonly reported source of funding. More than 70% of trials enrolled fewer than 500 patients. Thrombolytic agents were the most common therapeutic class investigated, followed by antithrombotics. The majority of trials were performed in patients with myocardial infarction. The presence of explicit age exclusion criteria declined from 58% between 1966–1990 to 40% in the decade 1991–2000 and the percentage of patients older than 75 years increased in the same period from 2% to 9%. These changes represented an improvement compared with the findings of the previous study by Gurwitz, but still failed to a large extent to correct the under‐representation of older people in these clinical trials.
More recently, van Spall et al. searched papers reporting RCTs in a number of conditions published between 1994 and 2006 in high impact factor medical journals, and extracted information on trial characteristics and patient exclusion [12]. In the context of each of 283 RCTs and the condition studied, the authors assessed whether exclusion was justified. The justified exclusions were classified as follows: (1) impossibility of granting of informed consent; (2) allocation to intervention or placebo group likely to harm the subject; (3) probable lack of effectiveness; or (4) the effect of intervention would be difficult to interpret. The researchers found that common medical conditions formed the basis for exclusion in 81.3% of trials while patients were excluded due to age in 72.1% of all trials (60.1% in pediatric populations and 38.5% in older adults). Moreover, individuals receiving commonly prescribed medications were excluded in 54.1% of trials. Surprisingly, only 47.2% of exclusion criteria were rated as strongly justified by Van Spall. Multivariable analyses revealed independent associations between the total number of exclusion criteria and drug intervention trials (risk ratio, 1.35; 95% confidence interval, 1.11–1.65; p = .003) and between the total number of exclusion criteria and multicenter trials (risk ratio, 1.26; 95% confidence interval, 1.06–1.52; p = .009). Industry‐sponsored trials were more likely to exclude individuals due to concomitant medication use, medical comorbidities, and age. Drug intervention trials, compared to other type of trials (devise, surgery, and other) were more likely to exclude individuals due to concomitant medication use, medical comorbidities, female sex, and socio‐economic status.
The exclusion of older patients from clinical research was also confirmed for several other common conditions of advanced age, such as heart failure [13, 14], cancer [15, 16], Alzheimer’s disease [17], urinary incontinence [18], the evaluation of influenza vaccination [19], and diabetes [20].
Older people are excluded not only by putting arbitrary upper age limits in trial protocols [21, 22], but more often by means of indirect criteria, such as comorbidity, concomitant drug therapy, reduced life expectancy, nursing home residence, and perception of poor compliance. This implies that even when older patients are recruited in clinical research, they are usually healthier and less disabled than those suffering from the same condition living in the community or encountered in clinical practice [14, 23].
Causes and consequences of the exclusion of older people
The reasons underlying the exclusion of older subjects from clinical trials are many [24]. Some characteristics of older patients are considered potential issues for the design and conduct of clinical trials. Older participants are highly heterogeneous, in terms of physical health, cognitive function, and disability. Therefore, trial sponsors and investigators are concerned that their inclusion might dilute any active treatment effect and potentially lead to statistically non‐significant results. The dropout rate is usually higher in trials involving older participants, due to a higher likelihood of becoming ill or dying during the trial, to relocation (institutionalization), or the unavailability of family members or caregivers to bring the older participants to the study site for follow‐up evaluations. As a consequence, a larger number of subjects are likely to be required to enter the study in order to maintain adequate statistical power. The issue of obtaining informed consent is also important because of the high prevalence of neurological and psychiatric disorders in older participants [25]. Another issue that might explain the under‐representation of older subjects is ageism, i.e. age‐related discrimination [26]. Moreover, whenever a drug therapy is evaluated, there is always concern about the risk of drug–drug interactions, lower compliance, and adverse drug effects because of the multiple drugs patients are already taking. Other barriers include the need for extra time and resources to enroll older participants and keep them in the trial, with consequent higher costs. The perception of older people as a vulnerable population that might be endangered by the participation in research could also limit their inclusion. Although older participants are often willing to participate in clinical studies [27, 28], there is some evidence that lower educational attainment, low socio‐economic status, the perception of excessive intrusiveness of the study in terms of collection of biological samples, duration of interviews, and transportation problems are all factors that might reduce their participation in research studies [24, 29].
The main consequence of the under‐representation of older people in clinical trials is that the majority of drugs, as well as many non‐pharmacological interventions, have been investigated only in few and usually highly selected older patients. This poses a challenge to the generalizability or external validity of their
results. The implication is that the value of many therapeutic interventions is not known in older subjects and healthcare professionals have to rely on studies performed on younger and healthier patients. However, since older people, and particularly the oldest subjects, i.e. over 85 years of age, are clearly different from younger adults, due to the interplay between aging, chronic diseases, polypharmacy, and lifestyle, there are inherent dangers in this forced necessity.
There is compelling evidence that the results of trials performed in younger adult populations cannot be automatically applied to older populations, both in terms of efficacy and safety. With regard to efficacy, the treatment of hypertension provides a clear example. While the treatment of systolic hypertension is beneficial in older adults, until a few years ago trials included only a limited number of participants aged 80 and older. The available data in this age group suggested that the pharmacological reduction of blood pressure decreased the risk of stroke but with a tendency toward a greater risk of mortality [30]. The pilot Hypertension in the Very Elderly Trial confirmed these ambivalent results [31]. On this basis, some experts opposed the treatment of high blood pressure in octogenarians [32]. Contrary to the expectations, a subsequent large trial provided evidence that treating hypertension reduces the risk of mortality from stroke, heart failure, and other cardiovascular diseases, as well as total mortality in a very old population, when patients were treated with the aim of achieving a target systolic blood pressure of 150 mmHg [33]. These results therefore demonstrate both that hypertension should be treated, at least in relatively fit older people aged 80 and older, as well as that the target for treatment is higher than in younger people.
Analogously, the inclusion of representative older patients is important to characterize the safety of a drug. A large randomized trial (Randomized Aldactone Evaluation Study, RALES) demonstrated that the use of spironolactone significantly improved outcomes in participants with severe heart failure [34]. Some years after its publication, there was a significant increase in the rate of prescriptions for spironolactone and also in hyperkalemia‐associated morbidity and mortality [35]. One possible explanation for these findings is that patients treated in clinical practice were much older, usually female, and with higher prevalence of diabetes and renal failure, than those included in the RALES trial [36]. In essence, the lack of an appropriate evidence base for prescribing therapies in older patients makes the activity of physicians extremely complex and prone to the risk of both over‐treatment and under‐treatment.
the preDICt study
As previously stated, older people account for high drug consumption, up to 60% in some countries, and they also often use non‐pharmacological treatments but they have often been under‐represented in clinical trials. PREDICT was the
Table 1.1 Participating centres and principal investigators in the PREDICT project.
Participant organization name
Medical Economics and Research Centre Royal Hallamshire Hospital, Sheffield (Coordinator)
Institute of Gerontology and Geriatrics, Department of Clinical and Experimental Medicine
University of Perugia Medical School, Perugia
Keele Interdisciplinary Research Centre on Ageing (KIRCA). Institute for Life Course Studies, Keele University
Department of Internal Medicine and Geriatrics Sabadell
Department of Nursing Home Medicine and EMGO Institute University Medical Centre
Amsterdam
Institute of Public Health, Krakow Jagiellonian University Medical College. Krakow
Geriatric Clinic Kaunas University of Medicine, Kaunas.
Country
UK
Italy
UK
Principal Investigator
Prof. David Edbrooke/Dr Gary Mills
Prof. Antonio Cherubini
Prof. Peter Crome
Spain Dr Joaquim Oristrell Salva
Holland
Poland
Lithuania
Ana Aslan National Institute of Geriatrics, Otopeni Romania
Dept of Geriatrics Soroka Hospital, Ben‐Gurion University Beer‐sheva
Department of Geriatrics First Faculty of Medicine, Charles University, Prague
Medical Research Council
Israel
Czech Republic
Prof. Cees Hertogh
Prof. Katarzyna Szczerbinška
Prof. Vita Lesauskaite
Prof. Gabriel Prada
Dr. Mark Clarfield
Prof. Eva Topinkova
UK Dr Paul Dieppe
acronym used for the Increasing the Participation of Elderly in Clinical Trials project. This project was funded by the European Commission within the Seventh Framework program and it was undertaken between 2008 and 2010. The PREDICT partners were based in the Czech Republic, Israel, Italy, Lithuania, the Netherlands, Poland, Romania, Spain, and the United Kingdom and co‐ordinated from MERCS, based in Sheffield, in the United Kingdom (Table 1.1). The aim of the project was to help identify, address, and resolve the issues related to the exclusion of older people from clinical trials.
The project was organized into five different work packages (WP). Work package 1 (WP1) was divided into two different parts: WP 1a was a systematic review of the literature to assess the extent of exclusion of the elderly from clinical trials in different conditions, chosen for their high prevalence and importance in older patients. WP 1b investigated ongoing clinical trials in heart failure to see whether the exclusion of older patients was still present in studies that would report in the years immediately after PREDICT had ended. WP2 and WP3 investigated the reasons why older people are under‐represented in clinical trials and what can be done to improve their participation. In WP2, the opinion of professionals involved in clinical trials was sought by means of a questionnaire
while in WP3 patients and their carers were invited to participate in focus groups that explored their understanding, views, and opinions on this topic. WP4 aimed at developing, based on the findings of the other WPs, a Charter on the Rights of Older People to participate in clinical trials. WP5 was devoted to dissemination.
Work package 1a
This work package performed a systematic review of studies of older people and their representation in clinical trials with the aim of answering three main questions:
1 Are older people under‐represented inappropriately in clinical trials for specified conditions?
2 What is the explanation of any under‐representation of older people in trials?
3 How can the representation of older people in clinical trials be improved? It was decided to investigate six conditions that are both prevalent and important in the older population. The conditions were dementia, colon cancer, heart failure, depression, hypertension, and the secondary prevention of coronary heart disease with statins. The systematic review was performed on the following databases: MEDLINE (1966 to Feb. 2008), EMBASE (1980 to Feb. 2008), ISI Web of Science (1900 to Feb. 2008), CINAHL (1982 to Feb. 2008), PsycINFO (1987 to Feb. 2008), ASSIA (1987 to Feb. 2008), the Cochrane Methodology Register, the Cochrane Database of Systematic Reviews, the HTA database on The Cochrane Library. Additional studies were identified by reviewing the reference lists of the identified articles. The search retrieved 5380 articles, of which 380 were identified as potentially relevant. The main findings of the review are reported here. The mean age of the participants in the heart failure trials was 61–63 years compared with the age at first diagnosis in clinical practice of 74–78 years. Nearly 30% of trials specifically excluded older people and fewer than 10% of trials included patients aged over 80 years. Patients enrolled in heart failure clinical trials tend to have more severe left ventricular failure, less comorbidity, and have coronary artery disease as the cause. In hypertension, it was found that the weighted mean age of patients in trials was 63.5 years. However, the age‐specific incidence of hypertension reaches a maximum at ages 65–69 years and remains at this level until ages 80–84 years. Thirty percent of patients diagnosed with hypertension are aged 75 years or older and 44% are 70 years or older. Only one large trial has studied the treatment of hypertension in people aged 80 years or above. Trial participants tended to have fewer cardiovascular risk factors, comorbidities, and cardiovascular disease than the general older hypertensive population. In Alzheimer’s disease, the mean age of the patients included in trials was less than 75 years. The age distribution of people with Alzheimer‘s disease is broad and for trials to be truly representative of the affected population, they should include a large proportion aged between 75 and 90 years. People participating in trials were more likely to be younger,
male, have a higher income, and have been educated to college level. In advanced colorectal cancer, the median age of patients included in trials was 62 years. This was considerably younger than the median age of diagnosis which in the period 1992–2001 was 70 years. Only 29% of trials had an upper age limit but several authors suggest that oncologists are uncomfortable enrolling older patients into trials.
Depression is one of the most common mental disorders in older people, and considering the demographic changes in the developed and developing countries, it is becoming a major public health problem [37]. From a clinical point of view, depression in older people is associated with functional decline, greater morbidity, increased risk of hospital admission, institutionalization, and overall mortality, due to increased risk of suicide and other causes, being responsible also for higher healthcare costs [38]. In this condition the evaluation of the literature did not provide clear evidence that older patients were under‐represented.
Subsequently, the researchers searched for surveys, qualitative studies, and reports of trial experiences that have identified barriers to participation in clinical trials and factors that may improve or promote participation. This search was limited to studies in or at least including older people and which had appropriate methodology. The data was summarized in the form of a qualitative overview with no attempt to quantify the importance of each barrier or promoter. Barriers and promoters were divided into those pertaining to patients and those relevant to healthcare professionals. The barriers to participation that were identified by health professionals were: (1) absence of an obligation for pharmaceutical companies to conduct RCTs in older people; (2) perception of the implications of trial participation for the patient; (3) perception of the implications of trial participation for their clinical practice, and (4) physicians’ views on the research topic. The barriers to participation identified by patients were: (1) unwillingness to compromise current care; (2) risk and fear of trial treatment; (3) problems with transport and access; (4) dislike of randomization and being experimented on; (5) time/scheduling conflicts; (6) financial implications; (7) the need to take care of dependents; (8) quality of information; (9) lack of interest; (10) poor self‐rated health; and (11) concerns about information and consent.
The only factor identified by health professionals as a promoter was found in cancer patients, the involvement of a cancer specialist in recruitment, while the promoters of participation identified by patients were perceived health benefits, altruism, improved healthcare and understanding, financial incentives, and social interaction.
Table 1.2 shows strategies to improve participation of older people, subdivided into different aspects of clinical trial delivery.
Finally, the authors identified RCTs that attempted to improve recruitment or retention of older patients in RCTs. Only five trials were found, evaluating different interventions. One trial evaluated recruitment methods, two trials evaluated methods targeting consent procedures, one study targeted patient adherence,
Table 1.2 Strategies to improve participation of older people in clinical trials.
Commissioners and ethics committees
Eligibility criteria in clinical trials should be justified by trial designers
Trial design
Minimisation of exclusion criteria
Inclusion of patient preference arm
Larger sample size
Involvement of clinical staff in research design and implementation
Simplified protocols
Minimal demands on clinical and support staff
On‐site coordination by clinical staff
Employment of data manager
Training for research staff
Conducting trials in well‐established clinical settings
Comprehensive geriatric assessment
Recruitment process
Recruitment by specialized research staff/principal investigator/general practitioner/specialist clinic/older people/research nurse
Recognition and understanding of culture of different ethnic groups
Mass marketing and advertising
Follow‐up of postal contact with a telephone call
Community outreach, health fairs, lectures
Personalized and face‐to‐face recruitment
Initial communication with trusted professional
Emphasize benefits of participation to others
Make expectations clear at initial contact
Easy physical access to research institutions
Provide transport or help arrange lifts, reimburse transport costs and parking
Offer home visit
Allow sufficient study time
Extended patient recruitment period
Financial incentives
Trial adherence
Be alert and responsive to potential signs of drop‐out and problem solve
Remind of commitment, reiterate motivations, emphasize need for complete data
Minimize respondent burden and give control to participants
Give tangible support
Enlist support from relatives, friends, physician, and healthcare professionals
Establish best time to call, including evenings and weekends. Flexibility
Schedule study visits to coincide with other appointments (e.g. outpatient visit)
Frequent follow‐up and contact
Individualize number of contacts, if perceived as too much of a burden
Reminder letters prior to visit
Home assessment visits
Offer phone/postal/e‐mail/surrogate follow‐up. Pay postage costs
Provide incentives or small tokens of appreciation, study specific items
Birthday/Christmas/thank you/illness cards
Newsletters/feedback on study
and one study aimed at improving professional compliance in a trial. No trial evaluated simple interventions to address barriers such as transportation issues, inconvenient timing, or care of dependents. Therefore, there is scanty evidence available on effective interventions to increase recruitment and retention of older participants in clinical research.
Work package 1b
There is a long time delay between the design of a clinical trial and the publication of its results. The aim of this WP was to investigate whether exclusion of older people is reducing as a consequence of a greater awareness of population aging and of a higher adherence of investigators to the recommendation provided by regulatory agencies to include older people in clinical trials [39, 40] (Box 1.1).
In order to address this research question, it was decided to analyze the characteristics of ongoing CTs by examining the online open‐access CT registry platform maintained by the World Health Organization (WHO) [41]. The aims of this WP were to assess the extent of under‐representation of older individuals in ongoing CTs, to evaluate the justifications for their exclusion, and to assess associations between trial characteristics and the exclusion criteria that have been applied. Heart failure was identified as a suitable target condition to study.
Older persons are more susceptible to develop heart failure (HF) due to the combination of age‐related changes in the cardiovascular system and the high prevalence of cardiovascular diseases. Presently 80% of all cases of HF occur in persons aged 65 years and older [42] and, as a consequence of population aging, it has been estimated that the number of older adults with HF will sharply increase. For example, in the United States, this number is projected to double in the near future [43]. HF is also the main cause of hospital admission in this age group [44]. However, there is a dearth of research specifically targeting older
Box 1.1 Documents of drug regulatory agencies concerning older people in clinical trials issued before the PREDICT study
Since the late 1980s, the main regulatory agencies that oversee drug authorization in Europe (the European Medicine Agency, EMA) and in the United States (the Food and Drug Administration, the FDA) as well as the organization that includes the drug regulatory agencies worldwide (the International Conference of Harmonization, the ICH), have been aware of the paucity of information concerning the efficacy and safety of drugs in older adults. In 1989, the FDA first released official guidance on the study of drugs likely to be used in older adults [39]. This document clearly stated that advanced age should not be a barrier to participation in clinical trials and that study participants should reflect as much as possible the population that will receive the drug once marketed, i.e. “for drugs likely to be used in the elderly, older patients should be included in clinical trials in reasonable numbers.” These principles were later adopted in an official ICH document [40].
HF patients. As already pointed out, about 30% of relevant clinical trials (CTs) excluded older persons and only 15% included patients aged over 80 years [13].
Information regarding ongoing CTs was obtained on December 1, 2008, from the WHO International Clinical Trials Registry Platform [41]. There were 378 registered trials recruiting patients with HF. A total of 127 studies were excluded: 79 because they had an observational design, 40 because they did not have HF as the main target condition, 6 because they investigated the physiopathology of HF, 1 because it was registered twice, and 1 because it involved children. Our analysis focused on the remaining 251 CTs (66.4%). Most CTs (220 = 87.3%) were extracted from the US registry (www.clinicaltrials.gov).
Most investigated non‐pharmacologic interventions (156 = 62.2%), were performed in a single center (161= 64.1%), and were sponsored by public institutions (155 = 61.6%). We found that 64 CTs (25.5%) excluded patients by an upper age limit. This age varied between 65 and 95 years, with a median value of 80 years. The percentage of trials having this exclusion criterion was similar in the period 2002–2006 and in more recent years. Drug trials sponsored by public institutions had significantly higher rates of exclusion than drug trials sponsored by private entities. Moreover, exclusion by upper age limit was significantly more common in trials conducted in the European Union than in the United States. The most common exclusion criteria in the evaluated CTs were related to comorbidity (n = 201, 80.1% of CTs). Exclusion by specific comorbidities, such as renal disease, was observed in 190 CTs (75.7%), whereas 26 CTs (10.4%) excluded patients by comorbidity expressed as the presence of another generic disease.
In 91 CTs (36.3%), patients were excluded because of reduced life expectancy while drug therapy was an exclusion criterion in about one‐fifth of the CTs (47 = 18.7%) and cognitive impairment in 32 (12.7%). Exclusion because of physical impairment was found in 35 CTs (13.9%). Standardized criteria were adopted to judge the appropriateness of exclusion criteria, based on a modification of methodology previously developed [12]. Applying these criteria, we found that almost half of the CTs (109 = 43.4%) had at least one poorly justified exclusion criterion, with similar proportions in pharmacologic and non‐pharmacologic trials. In conclusion, the PREDICT study found that ongoing CTs, that will influence clinical practice in the field of heart failure in the near future, still discriminate against older individuals.
Work package 2
This WP aimed at collecting the opinion of relevant professionals about the exclusion of older people from clinical trials [45]. A structured questionnaire was administered to a convenience sample of six professional groups: geriatricians, general practitioners, nurses, clinical researchers, ethicists, and pharmacologists/pharmacists working in the pharmaceutical industry in nine countries (the Czech Republic, Israel, Italy, Lithuania, the Netherlands, Poland, Romania,
Spain, and the UK). A sample size of 540 professionals (almost ten from each of the six professions from each country) was considered adequate to provide an overall view and to offer an indication of inter‐nation and inter‐professional differences. A Delphi approach was used to develop the questionnaire using the information derived from the results of WP1a and WP1b. A pilot study was conducted in which the questionnaire was completed by two individuals from each professional group in each country (n = 46). The findings of this study were discussed in order to develop the final version which comprised three closed questions requiring a yes/no response and 43 questions asking respondents to rate their agreement/disagreement with a statement using a 6‐point Likert scale. Furthermore, there was an opportunity to provide free‐text supplementary responses. The questions investigated the under‐representation of older people in clinical trials, the barriers to and promoters of the inclusion of older people in clinical trials, and potential improvements and regulation of clinical trials. Responses to the yes/no questions were analyzed as such. Responses to the Likert questions (strongly disagree, disagree, somewhat disagree, somewhat agree, agree, strongly agree)were dichotomized into either agree or disagree. A response rate of about 90% was achieved with 521 questionnaires returned. The detailed results are reported in the original paper [45]. The majority of respondents had previously been involved in clinical trials, the exception being nurses and GPs, of whom only 27% and 47%, respectively, had participated. Respondents believed that older people were under‐represented in clinical trials (84%), that this under‐representation caused difficulties for clinicians (79%) and that older people were disadvantaged as a result (73%). In answering questions about the justification of the exclusion criteria, about half of the responders believed that it might be justified to exclude older people in the clinical trial design, due to polypharmacy or comorbidity, while all the other criteria were not accepted by the majority of professionals. Only 18% agreed that it is possible to apply results obtained in younger patients to older patients and only 13% believed that upper age limits were justified. Nevertheless, the responders estimated that physicians would still be reluctant to recruit older patients, even in the absence of explicit upper age limits, mainly due to comorbidity, polypharmacy, risk of adverse drug reactions, and cognitive impairment.
In response to questions about promoters to the inclusion of patients for physicians, the majority of people questioned agreed that it would be important to make a specific requirement for the recruitment of older subjects, to set specific age‐related recruitment figures and to offer an increased amount of money to those undertaking trials to take into account the potential extra work needed. At the patient level, some factors were deemed important by more than 90% of responders, for example, follow‐up evaluations performed at home, encouragement by their doctors, simplification of trials, flexible appointments, reimbursement of transport costs, and staff using a reassuring manner when conducting trials. Slightly lower numbers supported other potential promoting
factors, such as entry recommended by a specialist, free care for treatment or follow‐up, and if patients/carers regarded their participation as altruistic. Finally, the majority of respondents agreed that clinical trial sponsors would be more likely to recruit older people if they could receive appropriate financial compensation, for example, extension of the drug patent (87%) or if there were a legal requirement to include older people in clinical trials (88%). An extremely interesting finding of the survey is that about 70% of responders believed that the present arrangements for inclusion of older patients in clinical trials were unsatisfactory and 60% agreed with the statement that the regulation of clinical trials needed to be revised.
The study revealed some differences between healthcare professionals coming from different countries. Respondents from the older EU countries (Italy, the Netherlands, Spain, and the UK) often gave quite different answers compared with those from the other countries (the Czech Republic, Israel, Lithuania, Poland, and Romania). In essence, the exclusion of older people from clinical trials was considered more problematic and less justified by professionals from the old EU countries. Although a total of more than 500 responses were obtained, the number in each national professional group was small, and this together with possible subject selection bias means that inter‐nation and group differences need to be interpreted with some caution. Nevertheless, it is possible that the views of health professionals in these different countries do reflect their diverse socio‐economic backgrounds as well as their knowledge of clinical trials. Thus, respondents from the new member states of the EU which have in general younger populations and lower economic resources, might confer a lower priority to research studies performed specifically in the older population. Differences emerged between professional groups. Geriatricians were the most supportive of the need to change the current trial regulations whilst those coming from the pharmaceutical industry were the least keen to agree with this statement.
Work package 3
The aim of this WP was to understand older people’s and their informal carers’ views on whether or not older patients should be included in clinical trials [46]. More specifically, the research sought to explore whether there were particular conditions under which older patients should or should not be invited to participate, whether there were any identifiable barriers or facilitators to such participation, and whether people felt that any additional guidelines or legislation were necessary to support appropriate inclusion. The methodology chosen was a qualitative one, that is, the structured focus group method. This method allows for the exploration of a tightly defined topic by individuals involved in a particular situation and is suitable for topics that are not considered deeply personal. It also allows for the collaborative construction of meaning, encouraging exploration and debate within the group and is particularly suited to accessing lay knowledge [47].
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This loan-office law was, however, the last in Pennsylvania.[208] The establishment of banks, for facilitating the purposes of trade, together with the great improvements and wealth to which the landed interest of the state had attained, by means of a widely extended foreign commerce, coming in aid of the benefits which the cultivators had previously derived from the loan-office system, superseded, in a great degree, the utility of this institution. In one year after the last loan-office was erected, the law for that purpose was repealed; the repealing act declaring—that it had been found inexpedient, and not to answer the purposes intended by the legislature. In fact, the establishment of banks in the interior of the country, not only supplies the place of a loan-office, in relation to the farmer, but greatly facilitates the extensive inland trade of the state. Experience has demonstrated, that, operating in this way, they are productive of all the important advantages of the loan-office system: and of this institution, the late governor Pownall speaks in these remarkable words—“I will venture to say, that there never was a wiser or a better
measure; never one better calculated to serve the uses of an increasing country; that there never was a measure more steadily pursued, or more faithfully executed, for forty years together,[209] than the loan-office in Pennsylvania, formed and administered by the assembly of that province.”[210]
In the year 1782, Mr. Rittenhouse was elected a Fellow of the Academy of Arts and Sciences, of Boston: his certificate bears date the 30th of January, in that year. This academy, which Dr. Morse ranks among the first literary institutions in the state of Massachusetts, holds a very respectable station in relation to science: yet it was not established till so lately as May 4, 1780. The end and design of the institution are stated to be—“to promote and encourage the knowledge of the antiquities of America, and of the natural history of the country, and to determine the uses to which its various natural productions may be applied: also, to promote and encourage medical discoveries, mathematical disquisitions, philosophical enquiries and experiments; astronomical, meteorological and geographical observations, improvements in agriculture, arts, manufactures, commerce, and the cultivation of every science that may tend to advance a free, independent and virtuous people.”[211]
It is supposed to have been somewhat about this time, that Mr. Rittenhouse exercised his ingenuity upon an object, which, though not of great importance, is nevertheless a matter of considerable utility and some curiosity; the invention of an Hygrometer, made wholly of wood. The simplicity of the construction of this instrument, renders it easily attainable by almost every one; and as it is found to answer, very well, the end for which more expensive instruments are often employed, it may be considered as being more generally useful. Descriptions of the construction, and principle of operation, of this Hygrometer, having been furnished to the writer through the obligingness of two of his friends,[212] a very concise account of it, drawn up from those descriptions, is given in the Appendix.
A circumstance shall be noticed in this place, which, although trivial in itself, will serve to shew the grateful sense entertained by our Philosopher of the merits of General Washington. It appears, that just about the time when the provisional articles of peace, concluded on between the United States and Great-Britain, were made known in America, Mr. Rittenhouse had forwarded to the General, at the head-quarters of the army, a pair of spectacles, and reading glasses, —as a small testimonial of his respect for the character and services of that great man. The terms of the letter that accompanied this little present, are not known to the writer of these memoirs; but, of what complexion they were, may be inferred from the General’s answer, which is in these words:
“Newburgh, 16th Feb. 1783.
“Sir,
“I have been honoured with your letter of the 7th, and beg you to accept my sincere thanks, for the favor conferred on me, in the Glasses—which are very fine; but more particularly, for the flattering expressions which accompanied the present.
“The Spectacles suit my eyes extremely well—as I am persuaded the Reading-Glasses also will, when I get more accustomed to the use of them. At present, I find some difficulty in coming at the proper focus; but when I do obtain it, they magnify perfectly, and shew those letters very distinctly, which at first appear like a mist—blended together and confused. With great esteem and respect, I am, Sir, your most obedient and humble servant,
“G . W .
“D R , Esq.”
The grinding and polishing of the glasses were of Mr. Rittenhouse’s own workmanship; and they were made for the purpose. This circumstance, added to the manner and occasion of
their being presented, could not fail of being highly acceptable to the General.
In the year 1784, Mr. Rittenhouse was employed on the part of Pennsylvania, for the purpose of determining the western extension of that state; and was associated in that business with Mr. Lukens, Dr. Ewing, and Capt. Hutchins: the commissioners in behalf of Virginia were Dr. (afterwards bishop) Madison, Mr. Ellicott,[213] Mr. J. Page, and the Rev. Mr. R. Andrews. A record of the astronomical observations which were made on this occasion, and on similar ones of an important nature, will be found detailed in a letter, under the date of April 2, 1795, addressed by Mr. Ellicott to Mr. Patterson, in the fourth volume of the Am. Philos. Society’s Transactions. Among the observations contained in the first part of that letter, are those of the immersions of the satellites of Jupiter, taken at Wilmington on the Delaware, by Messrs. Rittenhouse, Lukens, Page and Andrews, at divers days from the 1st to the 23d of August, in the year 1784; together with those taken at the western observatory by Messrs. Ellicott, Ewing, Madison and Hutchins, at divers days from the 17th of July to the 19th of August; also, the emersions of those satellites by the same eastern observers, from the 29th of August to the 19th of September; and by the same western observers, from the 27th of August to the 19th of September; all in the same year.
“After the determination,” says Mr. Ellicott, “we completed the southern boundary of Pennsylvania; it being likewise the north boundary of Maryland, and a part of Virginia; and which had been carried on some years before,[214] by Messrs. Mason and Dixon, the distance of 242 miles.” This line is in the parallel of 39° 43′ 18″ North latitude.[215]
It was at the close of this year, that the college of William and Mary, in Virginia, complimented Mr. Rittenhouse with an honorary degree of Master of Arts, by an unanimous vote of the rectors and faculty of that institution. His diploma, which is a special one, and wherein he is styled the Chief of Philosophers,[216] has a place in the Appendix.
The college of William and Mary was founded in the joint reign of the king and queen of those names, who endowed it with twenty thousand acres of land, besides a small duty on certain exported tobaccoes, granted by stat. 25 Ch. II: in addition to which, the assembly of Virginia also gave to it, by temporary laws, a duty on liquors imported, and on skins and furs exported. And from these resources, its funds amounted, on a medium, to more than 3,000l. Virginia currency, (or $10,000,) per annum. The Hon. Robert Boyle, [217] of England, had also made a liberal donation to this college, for the purpose of instituting a professorship, called the Brafferton, (the name of the English estate, purchased with the money granted by him to the college,) for the purpose of compensating missionaries, to instruct the Indian natives and to convert them to Christianity. After the revolution, the constitution of the college of William and Mary underwent a considerable change: three of the six original professorships, that is to say, two of Divinity, and one of the Greek and Latin languages, were abolished; and three others, namely, one for Law and Police—one for Anatomy and Medicine—and a third for Modern Languages, were substituted in their stead; the Brafferton, it is presumed, has been diverted into other channels, if not wholly neglected.
This once respectable college, or university, is at present in an unprosperous condition; and will not probably soon, if ever, regain its former reputation. A country of which a large portion of the population consists of slaves, is ill suited for the site of an extensive seminary of learning, and for the education of youth: nor can it be expected, that where an almost despotic sway of masters over their slaves[218] is daily exhibited to the view of both young and old, the children of those masters will submit to that degree of subordination, and to that exercise of authority by their literary preceptors, which the discipline of an academic education renders indispensable. The late Bishop Madison contributed much by his abilities, his suavity of manners and his prudence, to maintain a due degree of order in this institution, over which he long presided with distinguished reputation; but the death of that respectable man, it is feared, augurs ill for the future prosperity of the seminary.
In the year following, the tracing of a meridian, northward, for the western boundary of Pennsylvania,—and, consequently, the eastern boundary of part of Virginia,—was commenced, from the western end of the southern line of Pennsylvania before mentioned. On this occasion, Mr. Rittenhouse addressed the following letter to Mr. Ellicott.
“Philadelphia, April 28th, 1785.
“Dear Sir,
“For some months past I had not the least apprehension of being obliged to visit the Ohio, this spring; but our affairs have taken such a turn, that at present it is probable I shall meet you, at the time and place appointed. Capt. Hutchins has been sent for to New York, by Congress, as the trustees of the university will not consent to Dr. Ewing’s absence. One or other of us will certainly set off in a few days, to meet you: our waggons are already gone.
“I have earnestly recommended to council to commission you to act in behalf of Pennsylvania,[219] after we pass the Ohio; and the president directs me to inform you, that they mean to send you a commission for the purpose: I hope it will suit your convenience.
“I ought long since to have informed you, that you were elected a member of our Philosophical Society—I wish you would favour us with a communication, on any subject you please. Pray let me hear from you, before you leave Baltimore. Have you any account from Virginia? I am, dear sir, yours with respect and sincerity.
“D R .
“A E , Esq. Baltimore.”
This boundary-line was begun in May, 1785, by Messrs. Rittenhouse, Ellicott, Porter, and Nevill; assisted by the present Dr. Benjamin Smith Barton, then a youth about nineteen years of age, whose medical and other scientific acquirements rendered him, even
at that early period of life, an useful associate of the commissioners. Mr. Nevill (who was employed on the part of Virginia) left the other commissioners late in August; and Mr. Rittenhouse, about the middle of September.[220] Dr. Barton remained until some time in October, when these operations ceased for that season. The line then wanted about 55⅓ miles of being completed: and this part of it, to its intersection of the margin of Lake Erie, was finished in the following year, by Col. Porter and Alexander Maclain, Esq.[221]
It will be readily conceived, that a person of Mr. Rittenhouse’s delicate constitution, and regularity in his mode of living when at home, must have experienced much inconvenience and felt many privations of comfort, while climbing rugged mountains, traversing vast uncultivated forests, and sleeping in a tent, for successive months, as he was necessarily obliged to do, when employed on occasions of this kind. For, although the government afforded to the gentlemen engaged in these arduous services, very liberal accommodations, there were, nevertheless, numerous conveniencies which the nature of the duty to be performed rendered unattainable. Yet it is a fact, that Mr Rittenhouse always returned from these excursions with a better stock of health, than he sat out with; notwithstanding the hardships he sometimes endured, and the many unpleasant circumstances in regard to weather, diet, bedding, &c. which he was compelled to encounter. The two following letters, written by him to his wife, while he was engaged in the service of establishing the boundary-line last mentioned, will enable the reader to form a pretty good judgment of the kind of life he then passed. They will at the same time serve to shew, in some degree, the bent of his mind and the disposition of his heart.
The first of those letters, dated at “Wheeling Creek,” June 30th 1785, is in these words.
“My dearest H,
“I have not heard one word from Philadelphia, since I left you. About a month ago I wrote to you from Union Town, and I promise myself a letter from you by the first messenger from that place, who
is now daily expected. To-morrow Mr Armstrong sets off for Hanna’s Town, where he expects to meet brother Isaac Jacobs, so that I write in confidence of my letter reaching you.
“If I were to view only the dark side of my situation, I should complain that I am here secluded from the society of those I love, deprived of books and every other of my most favourite amusements; confined to homely fare by day, and a hard bed at night; and obliged, by our business, to take rather too much exercise. But these inconveniences are in some measure counterbalanced by several advantages: I am not condemned to hear that eternal din for money, which it pains me to think you are every day perplexed with;[222] politics have no existence here; constant and regular exercise causes me to sleep much better at nights, than I did at home;—we have a woman to cook for us, so that our bread is good, and every thing else tolerable. Colonel Porter is attentive, and cousin Benjamin[223] has recommended himself as an agreeable companion, to all of us; and I could almost call Mr. Ellicott a congenial soul.
“I ever delighted in a wild uncultivated country; this is truly romantic, and, at this season of the year, beautiful and luxuriant in the highest degree. A few days ago, I walked up a little rivulet, in company with Mr. Ellicott, for a considerable distance, in order to enjoy the romantic scene. It was bounded on each side by steep hills of an immense height: its bottom was finely paved with large flagstones, rising in steps, with, every now and then, a beautiful cascade. The further we went, the more gloomy and cool we found it. At last, I advised Mr. Ellicott that we should proceed no further; for, if we did, we should in all probability find some of the watergoddesses,—perhaps stark naked and fast asleep. Mr. A—— went with us, for company-sake; but neither the nymphs nor their shady bowers have any charms for him. [224]—Nothing but your company was wanting to me, to heighten the enchanting scene.
“Deer are incredibly plenty here—I was the first that caught a young fawn, and hoped to have sent the beautiful little animal a
present to H****. We kept it about a week, and it became quite tame; but our cows ran away, and it was starved for want of milk. Col. P. called it F—— B——, and says H**** shall at least have the skin. We have all been very healthy; my cough diminishes slowly, my old complaint is less troublesome, and I have no other.
“I am not yet determined, as to the time of my return. Later than September, I have no thoughts of staying; perhaps the fear of riding in hot weather may induce me to stay till then.
“We have, hitherto, made so slow a progress, that I am much dissatisfied with it; but do not know how to help it. Our greatest difficulty arises from the nature of the ground; and the idleness of the people of the country, is not the least. We have had about thirty men employed, and are not yet able to go more than a mile per day. I was about writing to the Vice-President, on this subject; but, on second thoughts, concluded it best not to do it: I wish, however, that council would, by some official letter, urge us to proceed with all the dispatch consistent with the accuracy they expect.
“I wish to write to B***** and H****; but you will not readily imagine how little leisure I have: Tired of the exercise of the day, I rejoice at the approach of night; and, after a cup of tea, generally lie down to rest as soon as it is dark, unless we have observations to make; and then we have generally half a mile to walk, through dark woods, from the place of observation to our encampment: this, however, does not happen above once in a fortnight.
“Sun, gallop down the western skies; Go quick to bed, and quickly rise;”
Until you bring round the happy day, that will restore me again to the dear woman and children I so much love.
“Give my love to my children, and the few friends that are really concerned for my welfare. God bless you, and make you at least as happy as I am; and then, I am sure, you will not complain. Your ever affectionate
“D. R
“Mrs. H R .”
The other letter, dated at the “Head Waters of Buffalo,” the thirteenth of July, is as follows.
“My dearest H,
“I need not say how much I feel for you, on account of the disagreeable situation in which you last wrote. The only advice, I believe, which I thought it necessary to give you, at leaving you, was to keep up your spirits and endeavour to bear the fatigues of the office. What will you say, or what will you think, when I tell you, I believe it scarcely possible for any thing to contribute so much to reconcile me to your absence, as the aversion I have to the plagues of that same office.
“You have heard the reports concerning the Indians. We are still ignorant of the true state of matters; but, from every information we can get, it seems very improbable that we shall cross the Ohio this summer: on this side of the river, we do not apprehend the least danger.
“On Saturday last, we suddenly emerged from the gloomy, uncultivated desert, into a habitable country; and encamped with joy in an open field where we could once more see the heavens around us,—a sight we had not been blest with, for five weeks past. Wheat, rye, and Indian-corn, growing, afforded a very pleasing sight; even the barking of dogs and crowing of cocks were agreeable. The next day being Sunday, several of the neighbours, their wives and daughters, paid us a visit; and amongst them, at least one spruce young lady, bred at the metropolis, Fort-Pitt.[225] But would you believe it? such is my unreasonable and incurable aversion to
company, that their visits soon became irksome. They hindered me from enjoying a lonely walk, or some passage in Milton,—or, perhaps, a loll on my bed. Nay, even our fellow-commissioners, the Virginians, I mean; I sometimes wish their wine was better, and flowed more plentifully: not that I might enjoy it with them; but that I might enjoy myself the more, alone.
“Whether you will believe me or not, I do not know; but my health is really much better. As I told you in my last, my old complaint is the only one I have; and this is, and has been for several weeks, infinitely more supportable, than I have known it for months together I do not, indeed, flatter myself with a cure; it is, in all probability, fixed for life: but an alleviation of the pain I have usually felt, is to me of much importance.
“We have, for three weeks past, had a much greater proportion of dry weather; and in this country, when it does not rain, the sky is always fair, of a beautiful blue, and the air serene. There has been nothing like a storm, nor scarce a puff of wind, since we came here. Though thunder, lightning, and rain, are so very frequent, they are never attended with high winds, nor scarcely a perceptible motion of the air. For a month past, we had a very decent woman to cook for us, but some little family broils obliged us to pack her home again. Our boys have, however, learnt from her to bake good bread, and to cook much better than they did. I mention this, because you will be pleased with any thing that can contribute to my comfort.
“I expect several opportunities of writing, before we reach the Ohio, none of which shall be neglected. I must lay down the pen, to retire to rest after the fatigues of the day. Wishing you a very good night, I conclude, &c. your ever affectionate
“D R .
“M . R .”
“P. S. Having mentioned the fatigues of the day, I must assure you that I find my strength fully equal to them: As to walking up the hills, I
never pretend to it, having always a horse to ride—Col. P is every thing I could wish; I mean, so far as is necessary to me.”
This arduous business of determining the territorial limits of several great states, which commenced before the American revolution, was not terminated until some years afterward. And on every occasion of that kind, where Mr. Rittenhouse’s situation, in respect to health and official duties, admitted of his being employed, his talents placed his services in requisition.
He had been at home but a few weeks, after being engaged in running the Western boundary of Pennsylvania, before he was elected by Congress, together with the Rev. Dr. Ewing, and Thomas Hutchins, Esq. afterwards Geographer of the United States, a commissioner “for running a line of jurisdiction between the states of Massachusetts and New-York, conformably to the laws of the said states.” This appointment was made on the 2d day of December, 1785.[226] It was not, however, until the year 1787, that the legislature of New-York ceded to the state of Massachusetts all the lands within their jurisdiction, Westward of a meridian to be drawn from a point in the Northern boundary of Pennsylvania, eighty-two miles West from the river Delaware; excepting one mile along the Eastern side of the Niagara river; and also ten townships between the Chenengo and Owegy rivers; reserving the jurisdiction to the state of New-York: a cession which was made to satisfy a claim of Massachusetts, founded upon their original charter.
This line was accordingly run, in the year 1787, by the commissioners so appointed for the purpose:—And “this last business, which was executed with his usual precision and integrity”—says Dr. Rush, speaking of Mr. Rittenhouse,—“ was his farewell peace-offering to the union and happiness of his country.”
It was not until the year 1786, that the American Philosophical Society were enabled to publish a second volume of their Transactions:[227] it then made its appearance. Into that volume is introduced a letter to the Society, in the original Latin, (accompanied with an English translation,)[228] from the celebrated C. Mayer, the Elector Palatine’s[229] Astronomer at Manheim, dated so long before as the 24th of April, 1778. The receipt of that letter had been acknowledged by Mr. Rittenhouse, according to a special order of the Society, so early as the 20th of August, 1779; and the answer, it is presumable, was duly transmitted to Mr Mayer Yet, although there was a lapse of seven years, from the date of Mr. Rittenhouse’s letter to the time of Mr. Mayer’s communication being printed in the Society’s Transactions, the former was, by some unaccountable circumstance, omitted and unnoticed! Nor will the reader’s surprise on this occasion be diminished, when he learns, that a member of the Society, having obtained from Mr. Rittenhouse a copy of his letter, had it read at their stated meeting on the 16th of March, 1792, —twelve years and a half after its date; that it was, thereupon, “referred to the committee of selection and publication:” and, notwithstanding, by some other fatality, that letter remained unpublished until now; being twenty-one years afterwards!
On a perusal of the answer to Mr. Mayer’s communication (in the Appendix,) it will be found, that the “eminent utility,” which he expected to result, at some future day, to astronomical science, from a prosecution of such discoveries as he had recently made among the fixed stars, had been long before anticipated by our Astronomer. In that answer Mr. Rittenhouse mentions, that he is induced to request his correspondent’s acceptance of a copy of the Oration he had delivered before the American Philosophical Society, “some years” before:—“because,” says the writer, “I therein gave my opinion, that the fixed stars afforded the most spacious field for the industry of future astronomers; and expressed my hopes, that the noblest mysteries would sometime be unfolded, in those immensely distant regions.”
This early opinion of his own concerning the fixed stars, to which Mr. Rittenhouse refers in his letter, is expressed in his Oration, in this short paragraph: “If astronomy shall again break those limits that now confine it, and expatiate freely in the superior celestial fields,— what amazing discoveries may yet be made among the fixed stars! That grand phænomenon the Milky way, seems to be the clue, that will one day guide us.”
Such were the expectations entertained by our Philosopher, more than three years before the date of Mr. Mayer’s communication of his discovery to the Philosophical Society;—a discovery which Mr Rittenhouse, in his letter to that great astronomer, styles “excellent;” and one that proves his own “presage” to have been well founded. He, at the same time, modestly suggests to Mr. Mayer, the institution of a comparison between the many observations he had already made, in order to determine, whether the several changes observed will agree with any imagined motion of our system; remarking, that those he had communicated, seemed to favour such a supposition.
How important soever, in relation to astronomy, the phænomena observed by Mayer may be, the honour of first discovering them certainly belongs to him. Mr. Rittenhouse was not the discoverer: nor had he ever access to so complete and expensive an astronomical apparatus, as that used by Mayer on the occasion, and with which he was furnished by means of princely munificence. But all candid men of science will, nevertheless, be disposed to allow the American Astronomer no inconsiderable share of merit for the early “presage,” which his deep-discerning and vastly comprehensive mind enabled him to suggest, of some such future discoveries.
The writer of these memoirs deemed it his duty to do justice to the memory of the subject of them, by giving publicity to these interesting circumstances; and the performance of this duty is the more gratifying to the writer, because he alone possesses a knowledge of all the facts he has stated, concerning them.
The late discoveries of Dr. Herschel, among the fixed stars, in addition to those previously made by Mr. Mayer, have in a greater
degree realised the expectations which were formed, many years before either, by our Astronomer; such, indeed, as are almost entitled to the character of prescient annunciations, respecting that portion of the heavens which should, some time or other, be the scene of the most important astronomical discoveries. According to Herschel, the Milky Way is an immense nebula, near one of the sides of which, is placed the solar system; and he imagines, that each nebula, of which he had observed more than nine hundred, consists of a group of suns, with their attendant planets!
Mr Rittenhouse never possessed the means of acquiring such stupendous and costly telescopes, as those used by Herschel, for the purpose of exploring the heavens. But the penetrating genius of our countryman seems to have contemplated, by anticipation, the actual existence of those sublime phænomena, some of which the vastly superior instruments of the Germano-Anglican Astronomer have since manifested; when, in language apparently prophetic, but certainly dictated by the most exalted pre-conceptions of the grandeur of celestial objects which were yet undiscovered, the American Philosopher observes, as he does in his Oration,—that “all yonder stars innumerable, with their dependencies, may perhaps compose but the leaf of a flower in the Creator’s garden, or a single pillar in the immense building of the Divine Architect.” Well might he exclaim, with rapturous extacy, after so beautiful and sublime a reflection,—“Here is ample provision made for the all-grasping mind of man!”
It will be evident to such as duly reflect on this subject, that those expectations which occupied the mind of Mr. Rittenhouse, so long since as the year 1775—concerning the “amazing discoveries” which should, at some future period, be made among the fixed stars, were not mere conjectures or vague hypotheses; but, that they were rational anticipations of realities, founded on the most acute observation and laborious research, as well as the profoundest philosophical judgment. As Newton is said to have revealed those truths in physics, which his predecessor, Bacon, had preconceived; so, that great practical astronomer, Herschel, and some other
eminent observers of our day,[230] have been enabled, by means of the very important improvements recently made in astronomical instruments,[231] to verify a grand hypothesis in his favourite science, which had long before been conceived by the towering genius of Rittenhouse.
From the time our astronomer became established in Philadelphia, until the year 1787, he resided in a house belonging to the late Mr. Thomas Clifford, at the south-east corner of Arch and (Delaware) Seventh streets: But the mansion which Mr. Rittenhouse had erected for himself, the preceding year, on his Observatory-lot at the diagonal corner of those streets, being then compleated, he removed thither; and there continued his residence, during the residue of his life. It was about this time, perhaps towards the close of the year 1786, that he was compelled by the duties of his office, as sole trustee of the loan-office, to put in suit the bonds which accompanied the mortgages of sundry delinquent loanees. The bonds were placed in the hands of the Writer of these Memoirs, for that purpose; with instructions to treat the delinquents with every reasonable degree of forbearance. This lenity was observed, agreeably to Mr Rittenhouse’s desire; few suits were instituted, and payment of the monies due, or the greater part of them, was not long after obtained.
Early in the year 1787, the expected appearance of a new comet in that year, engaged Mr. Rittenhouse’s attention: and on that occasion he addressed the following letter to Mr. Ellicott.
“Philadelphia, Feb. 12, 1787.
“Dear Sir,
“The elements of the new Planet have been pretty well determined by several European astronomers. The following I have extracted from the Almanack[232] for 1787. Mean Longitude 4
To Dec. 31, Mean Anomaly 4 8 53 56 1787, at noon,
Mean Motion in Long. in 365 days 4° 19′ 47″ in 30 days 21′ 21″ in 24 hours 42″.7
“The Aphelion and Nodes move according to the precession of the Equinoxes; that is 50″.3 per ann. Inclination of the Orbit 46′ 13″
Log. of greatest distance from the Sun 6.3007701
Log. of least distance 6.2594052
The Log. of the Earth’s mean dist. from ☉ being 5.0000000
“Dr. Halley’s Table of the equation of ♃’s orbit will do very well for computing the place of Herschel’s planet, only subtracting 1/16 part of the equation there found; the greatest equation of this planet being 5° 27′ 16″. So, if from the Log. to any degree of anomaly, in the Table for Jupiter, we subtract 1/76 part of the excess of that Log. above the least, and to the remainder add the constant Logarithm .5647750, we shall have the Log. for ♅ sufficiently accurate. On these principles, I have computed the Right Ascension of ♅, and find both agree with my own observation, to a few seconds.
“I am sorry you have engaged the notice of *******. Men of his principles, with a printing-press at command, are the greatest pests of society.
“My very bad state of health, and a multiplicity of business, have prevented my answering yours as soon as I wished to have done it. I am, Dear Sir, your Friend and Humble Servant,
“D R
“A
E , E . Baltimore.”
The correctness of the calculations respecting the Georgium Sidus, stated in this letter, is noticed in the following extract from one of Mr. Ellicott’s Almanacks.
“The reader will find in this Almanack a continuation of the planet ♅. The elements on which the calculations were made, appear by observation to be very accurately determined, not only by the astronomers in Europe, but by my ingenious friend Mr. Rittenhouse, whose knowledge of the theory and practice of astronomy, is not surpassed in the old world.”
From this time, until his resignation of the treasurership of Pennsylvania in the autumn of 1789[233] , Mr. Rittenhouse appears to have continued to be pretty much engaged in the duties of that office. A short time before this event, the Writer of these Memoirs visited the city of New-York; where the first congress, chosen under the present constitution of the United States, were then convened, having commenced their session on the fourth day of March preceding: and on that occasion, Mr. Rittenhouse addressed a letter to General Washington, then President of the United States, recommendatory of his friend and nephew. Delicacy forbids this relative to present to public view that portion of the letter, which more especially relates to himself: but the introductory part of it is here presented to the reader, for the purpose of testifying the continuance of the high esteem entertained for the truly great man to whom it was addressed, by one who never disguised his sentiments. This extract is as follows:
“Philadelphia, Aug. 14, 1789[234]
“Sir,
“However unwilling I am to add to that multitude of letters which must encroach so much on your precious time, I cannot altogether
forbear, without doing violence to my feelings. As we have, all of us, through the course of life, been greatly indebted to the good offices of others; so we are no doubt under obligations to perform the same in our turn, as well with respect to our particular friends, as society in general.
“Mr. William Barton, my sister’s son, knowing that you have heretofore honoured me with your acquaintance, I might, perhaps, say friendship, is willing to believe that any thing I can say in his favour, might have some weight with your Excellency.—
“Wishing your Excellency every happiness, I have the honour to be, Sir, with the greatest respect, your most obedient humble servant,
“D R .
“His
Excellency the President of the U. States.”
On the 10th of November, 1789, the following letter from Mr. Rittenhouse, offering his resignation of the office of treasurer of the state, was presented to the general assembly; and, after having been twice read, was, by order of the house, entered on their minutes.
November 9, 1789.
“Sir,
“On account of the very unfavourable state of my health, as well as because I most earnestly wish to devote some of the few remaining hours of my life to a favourite science, I find myself under the necessity of declining the office of treasurer.
“I have now held that office for almost thirteen years, having been annually appointed by the unanimous voice, so far as I know, of the representatives of the freemen of this state; a circumstance I shall ever reflect on with satisfaction, and which does me the greatest honour.
“I will not pay so ill a compliment to those I owe so much, as to suppose the principal motive in these repeated appointments was any other than the public good; but I am nevertheless very willing to believe, that a regard to my interest was not wholly out of view. And I shall, perhaps, never have another opportunity of expressing, with so much propriety, my sincerest gratitude to the representatives of my countrymen, whose favour I have indeed often experienced on other occasions.
“I accepted the treasury, when it was attended with difficulty and danger, and consequently when there was no compensation for it. Soon afterwards, a depreciated currency, prodigiously accumulated, made it extremely burthensome, without any prospect of profit.
“In a more favourable situation of our affairs, it might have been lucrative, had not the very small commissions allowed by law, been scarcely equal to the risk of receiving and paying. In 1785, my commissions were increased, and the office was for some time profitable; but the difficulties or remissness in collecting the public revenues, again reduced it to a very moderate compensation.
“If, however, the embarrassments of the office have, in general, been little understood by those not immediately concerned in it; if the emoluments of it have been greatly exaggerated in the public opinion; I am still the more obliged to the several assemblies, who, under these impressions, have nevertheless continued me so long their treasurer.
“The confidence of the public I have ever esteemed so invaluable a possession, that it has been my fixed determination not to forfeit it, by any voluntary act of impropriety. Where my conduct has been
