Major findings from Held-Hanno 1987–1990a
Supported by subsequent research
1
43,500–90,000 diagnosed cases of IC in the USA (Almost twice the Finish (Oravisto) estimate of 18 vs. Held et al. of 30/100,000 women)
Yes. All modern US estimates are higher than Held et al. including some as high as 7.9 M women.b Evolution of Nomenclature brought both IC and Bladder Pain Syndrome into one and the same disease: IC/BPS
2
Up to a fivefold increase in IC prevalence if all patients with painful bladder, sterile urine had been given the diagnosis, yielding up to half million possible cases in the USA
Yes; Definition has evolved to IC/BPS
3
Median age of onset: 40 years
Yes. E.g. Rand study: 45 years
4
Late deterioration in symptoms unusual
Yes
5
Ten times higher incidence of childhood bladder problems in IC patients vs. controls
Yes
6
Two times the incidence of a history of urinary tract infection vs. controls
Yes
7
Lower quality of life (QoL) than dialysis patients; Dyspareunia common.
Yes. All subsequent studies report low quality of life however using other comparison measures. E.g. “Lower in vitality and mental health”. “IC had significantly lower QoL scores in four of the seven quality of life dimensions”b
8
Medical treatment cost: $13.9K/patient/yr. Lost economic production:$15.2K/patient/yr. (2017 prices)
Yes; but cursory at best Using Jones & Nyberg prevalence of 500/100K population: $47B total economic cost/yr
9
Treatments Frequently Ineffective
Yes. Still the case; Two treatments that sometimes help: pelvic floor physical therapy; diet modification
10
Unable to work outside the home
Yes, but comparison group not given
Items 1 & 2. Prevalence, a central issue for study of any disease. Held-Hanno showed that the original study provided prevalence estimates that were far larger than the Finnish study. And clearly the right side of Table 3.1 indicates that practically all studies since have shown that prevalence is much higher than expected whether you use the baseline of Oravisto or Held-Hanno. As shown below (item 2), there was this ambiguity that occurred with the patient who experienced painful bladder and sterile urine but for whom there was no diagnosis of IC. So over this interim of 30 years, the evolution of thinking and classification of this disease resulted in combining the two notions into one IC/BPS.
But the right side of item 1 in Table 3.1 also identifies a major problem that has evolved from research and treatment of IC/BPS: there is considerable variance in these estimates especially if one includes the symptom studies. (e.g. Berry et all suggest there may be up to 7.9 million women in the US suffering from IC/S although only 10% have been given the diagnosis).
Items 3 & 4. While occurring in all ages, typically this disease occurs in middle age and the
“natural history of symptoms of IC … to be that of a sub acute onset with a rapid peak in severity, and then a relatively constant plateau of chronic symptoms thereafter. However, many patients do experience …remissions and flares in their disease symptoms.” [5]
Item 7. Quality of Life (QoL) The Held-Hanno study clearly showed that quality of life of IC/BPS patients was low and to make the measurement clear used a comparison group of patients living with chronic dialysis. All the subsequent studies, which addressed QoL, found much the same but provided comparisons that were not so obvious to benchmark.
Item 8. Costs were reported in many dimensions in the original study including estimates of medical care use (physician visits, hospital stays, insurance coverage and the like). Other cost measures included lost economic production attributed to IC/BPS because of lower labor force participation and lower wages when working in the labor force. Using the prevalence estimates of Jones and Nyberg (500/100,000 population) a projection of $47 billion economic cost per year including both medical care cost and lost economic production. However the studies in the interim had at best a weak focus on economics. In a section below we discuss at some length the significance of this omission.
Item 9. Treatments were frequently ineffective in the Held et al. study. And probably one of the most depressing news of this research arena is that the situation has not changed much since 1990. It is really depressing to report that there has been little progress in treating this chronic disease.
It has been 39 years since DMSO became the only FDA approved intravesical therapy for “interstitial cystitis”, and 21 years since pentosan polysulfate became the only orally approved medication for this condition. While many newer therapies seem to have some benefit (neuromodulation, botulinum toxin, cyclosporine), none have made the threshold of FDA approval for this condition, and the vast majority of therapies are off-label. Perhaps the biggest advance has been in the use of pelvic floor physical therapy as a staple of a conservative treatment approach.
Item 10. Other important measures like the ability to hold employment were captured by Held-Hanno and importantly had comparison groups that were easy to interpret. Basically these IC/BPS patients are frequently out of the work force because of their disease. Unfortunately, the interim studies did not pursue these questions very well.
Overall the Held–Hanno study of 1990 performed remarkably well. Virtually all of the basic findings reported in 1990 have been confirmed and amplified in many cases in the following 30 years. Perhaps the only major issue that was not pursued in the early period, which came out of the subsequent studies, was the epidemiology of males with IC/BPS.
3.3 Prevalence of IC/BPS
Prevalence, usually expressed as # cases/population, is one of the most fundamental measurements of epidemiology. How many cases have this disease or this condition? Estimating the prevalence is an extremely important research component in understanding and coping with the IC/BPS medical condition. Prevalence indicates just how “big” a medical problem is as well as providing an indication of how the disease incidence (new cases per unit of time) and prevalence is changing. In the case of IC/BPS, Orivisto’s 1975 study is generally considered an “original” if for no other reason than it was an early report. The study was based on a thorough examination of hospital records in one city in Finland in which was believed that all cases had a high likelihood of being counted. Four particular aspects of Oravisto estimates should be noted:
- 1.
The cases were “determined” to be interstitial cystitis (IC);
- 2.
Were diagnosed by a physician;
- 3.
Were measured per population estimates of women.
- 4.
Were based on a review of hospital records.
Subsequent work sometimes does and sometimes does not make these distinctions.
Prevalence estimate are important because:
- 1.
The magnitude of the problem, in even the simplest terms, can be determined: e.g. “More than 1.2 million people in the US are living with HIV.” But more quantitatively, prevalence is the starting point for almost all policy questions. If you doubt this speak sometime to the physicians and patients involved in what are considered “rare diseases”.
- 2.
When combined with some measure of the cost of treatment (e.g. medical expenditures per patient per year) of a disease, it provides policy and decision makers with considerable information in determining priorities in allocation of research moneys. Or look into the pharmaceutical industry as they decide on putting a few billion dollars investment for a new product. Do you think they do not take seriously prevalence estimates? Not a total picture by any means but part of the picture. See below which discusses this topic in more detail.
- 3.
As shown in Table 3.2, the National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK one of 27 institutes and centers that make up the NIH) in 2016 spent almost 1.6 billion dollars ($1,563,393,000) on extramural research (about 86% of the total NIDDK budget of $1.9B). Just over a quarter (28%) of the extramural budget of NIDDK was spent on research focused on kidney, urological and hematological diseases. What fraction went to urological diseases including IC/BPS was not available.
Table 3.2
National Institutes of Health
National Institute of Diabetes and Digestive Diseases and Kidney Diseases (NIDDK) | ||
|---|---|---|
Extramural Research | 2016 Fiscal Year | % |
Diabetes, Endocrinology and Metabolic Diseases | $641,483,000 | 41 |
Digestive Diseases and Nutrition | $482,533,000 | 31 |
Kidney Urologic and Hematologic Diseases | $439,377,000 | 28 |
Subtotal, Extramural Research | $1,563,393,000 | 100 |
The NIH/NIDDK decision process is clearly not a transparent function but one does not have to be a political genius to suppose that the social cost (money, quality of life, loss of life) of a disease plays a role in making decisions where to allocate extramural research funds. For example, in the case of renal failure, Medicare (the public institution in the US that “insures” the elderly, disabled and other categories of Americans) pays most of the bills for all dialysis and transplants regardless of age. But NIDDK puts a lot of research resources into the study of renal disease including end stage because it is very expensive in addition to being the cause of a lot of potentially preventable deaths. Politics plays a role too. Just look at the funding that went into the battles to treat AIDS.
3.3.1 What the Held-Hanno and Subsequent Studies Tell US About Prevalence of IC/BPS
Essentially, the older study and most all US studies since confirm that IC/BPS is a serious health problem facing America. And given that the medical world has few helpful treatments, it is even a bigger problem than most. When there is medical technology (e.g. pharmaceuticals) and the problem might be financial access, the solution may be simple at least conceptually i.e. find the financing to fix the problem. (Interestingly the Konkle et al. [6] study gives a passing indication that a non-trivial number of the patients in the RAND study did not have health insurance).
Table 3.3 provides an overview of the prevalence findings of the Held-Hanno study and the subsequent research following in the period 1990–2016. Jones and Nyberg [5] suggest there are 1.1 million persons in the US with IC/BPS. Given that their study was based on a well-researched and respected data source (National Health Interview Survey), their estimates should be given additional credence. Suskin et al. 2013, a reasonably recent study, suggests that there are 2.1 M men with IC/BPS although they note that many of these cases may be currently diagnosed as having chronic pelvic pain syndrome/nonbacterial prostatitis.
Table 3.3
Prevalence of BPS/IC: 1990 vs. 2016 (rate per 100,000 population shown in bold)
