# Presentation: 372559

## The Social Cost of Scientific Misconduct and Questionable Research Practices

**William Gardner, PhD****	**

**Center for Innovation in Pediatric Practice, **
**Columbus Children’s Research Institute**

**Departments of Pediatrics, Psychology, & Psychiatry**
**The Ohio State University**

- Supported by NIH/ORI: 1R01 NS49591.

## Social Costs of Research Misconduct (RM)

- How much should we care about RM?
- “A lot, because integrity is essential to science.”
- But why should non-scientists care about this?
- Consequentialist answer: “A lot, because research misconduct may have a large social cost.”
- My talk is conceptual, not empirical. I’ll define this social cost and suggest how to study it.

## Direct, Visible Economic Costs of Research Misconduct

- Steneck: What does the NIH lose from RM?
- ‘Direct’ Cost  *Loss* = Grant Award $s.
- ‘Visible’ Cost  Use only known RM cases.
*Loss */ *Year* = (*N *RM Cases* */ *Year*) x *Cost* / *Case*.
*Cost* / *Case* = $427K (Avg 2005 NIH award).
*N *RM Cases = 10 cases / *Year*.
- Therefore,* Loss / Year* = $4.3M.

## Direct, Invisible, Economic Costs of Research Misconduct

- ‘Invisible’ Cost  Impute rate of RM cases based on hypothesized incidence of RM.
*N *of NIH Grants* *(2005) = 47,345.

| Prevalence of RM | Imputed 2005 Loss |
| --- | --- |
| 1/1000 Grants | $20M |
| 1/500 Grants | $40M |
| 1/250 Grants | $81M |
| 1/100 Grants | $202M |

## Indirect Economic Costs of Research Misconduct

- ‘Indirect’ Cost  *Loss* = monetary value of benefits that society would have received from research, but did not.
- Challenge 1: Measure monetary value of science.
- Challenge 2: Identify the benefits that society did not receive because of RM.

## Two Thought Experiments

- Did research misconduct delay the start of smoking prevention efforts?
- Does research misconduct reduce the efficiency of pharmaceutical research?

## Thought Experiment: Scientific Misconduct & Smoking

- Massive behavior change, catalyzed by dissemination of scientific research.

## Reduction of CVD Mortality Attributable to Smoking Reduction

- Based on Cutler (2001).

- 4.5 years improvement in life expectancy over 50 years due to reduction in CVD mortality.

- Of that, 1.5 years reflects behavioral change.

- Of that, assume .75 years is smoking reduction.

## Additional Life-Years From CVD Mortality Reduction Attributable to Smoking Reduction

- Accumulate the per capita gain in chance of surviving a year across population.

## Annual Value (in $B) of CVD Mortality Reduction Attributable to Smoking Reduction

- Valuing a year of life at $100,000 (Murphy & Topel, 2001).

## What if the Surgeon General Spoke Out in 1959?

- Scientific debate about smoking was rife with misconduct.

- Counterfactual curve:
- Suppose that RM & QRP had not clouded the debate.
- Suppose that  prevention efforts had started 5 years earlier?

## Additional Benefit From Reduced CVD Mortality Attributable to Earlier Smoking Reduction

- Shaded area is the value of the reduction of CVD mortality, had we started 5 years earlier ( > $100B).

- Under these counterfactuals, these are the social losses attributable to RM.

- Moving prevention efforts forward 1 year saves $27B.

## Thought Experiment: Misconduct, QRP, & New Drugs

- RM & QRP results in the direct loss of investment.

- However, RM in the drug development may also reduce *N* of new drugs / $ invested.

- Fewer new effective drugs means less reduction in mortality. Indirect Cost = Value of life-years not saved.

## The Drug Development Process

- Drug development is a multiple stage process, from pre-clinical investigations through multiple phases of CTs.
- Later stages of development involving animals and humans are far more expensive than earlier stages.

| Clinically Useful Compounds Tested at Stage t | Useless Compounds Tested at Stage t |
| --- | --- |
| (N Useful Compounds at t-1) x (Sensitivity at t-1) | (N Useless Compounds at t-1) x (False Positive Rate at t-1) |

## Misconduct & The Drug Development Process

- Misconduct increases the False Positive Rate in the drug development process.
- Small increases in the False Positive Rate in drug testing will substantially increase the proportion of  useless compounds tested in expensive later stages.
- This wastes research dollars, a direct cost of RM.
- However, it also increases the investment cost of developing a useful drug  fewer drugs are developed.

## The Value of the Missing Drugs

- The indirect cost of RM in drug development are those missing drugs.
- Econometric models suggest that better drugs for CVD have a larger impact than smoking reduction.
- Hence the annual value of life-years saved due to improved CVD medication alone is worth tens of $B.
- Small inefficiencies in the drug development process will result in losses that are likely to be scaled in $B.

## Summary: Social Cost of Fraud in Pharmaceutical Research

- RM and QRP make it harder to eliminate bad ideas early, and may induce other researchers to pursue false leads, reducing research efficiency.
- Therefore, RM and QRP increase the cost of discovery, reduce the rate of discovery, and reduce the rate of growth of life expectancy.
- RM & QRP are like securities fraud: Society loses from both the loss of the investment and reduced economic growth from the misallocation of capital.

## So we have proved what, exactly?

- Buck Mulligan, in the Martello Tower, speaking of Stephan Dedalus:
- “It’s quite simple. He proves by algebra that Hamlet’s grandson is Shakespeare’s grandfather and that he himself is the ghost of his own father.”
- 	James Joyce, *Ulysses*

*I am waving my hands*. The point of waving my hands is to point out a new question, and suggest how we might try to answer it.

## Limitations of Thought Experiments

- Our examples do not include data on misconduct.
- Our arguments rely on economic models that are controversial.
- We consider only medical examples.

## Conclusion to Thought Experiments

- We have clarified the meaning of an indirect social cost of research misconduct.
- We have also clarified the stakes in RRI.
- Steneck’s estimate of the direct costs of RM were expressed in $M.
- I think the value of indirect social costs of RM should be expressed in $B (3 orders of magnitude).

## Conclusion: The Social Costs of Scientific Misconduct

- Because RM is relatively rare, the direct costs of RM are likely small.
- The social value of science, however, is titanic.
- Inefficiencies in technology transfer caused by RM should be projected across this large value.
- Social costs of RM are greater than are imaginged, and vastly greater than the cost of research on RI.