How blockchain-timestamped protocols could improve the trustworthiness of medical science

Trust in scientific research is diminished by evidence that data are being manipulated¹. Outcome switching, data dredging and selective publication are some of the problems that undermine the integrity of published research. The declaration of Helsinki states that every clinical trial must be registered in a publicly accessible database before recruitment of the first subject². Yet despite the creation of numerous trial registries problems such as differences between pre-specified and reported outcomes persist^3–5. If readers doubt the trustworthiness of scientific research then it is largely valueless to them and those they influence. Here we propose using a ‘blockchain’ as a low cost, independently verifiable method that could be widely and readily used to audit and confirm the reliability of scientific studies.

A blockchain is a distributed, permanent, timestamped public ledger of transactions. In doing so it provides a method for establishing the existence of a document at a particular time that can be independently verified by any interested party. When someone wishes to add to it, participants in the network – all of whom have copies of the existing blockchain – run algorithms to evaluate and verify the proposed action. Once the majority of ‘nodes’ confirm that a transaction is valid i.e. matches the blockchain history then the new transaction will be approved and added to the chain. Once a block of data is recorded on a blockchain ledger it is extremely difficult to change or remove it as doing so would require changing the record on many thousands computers worldwide. This prevents tampering or future revision of a submitted timestamped record. Such distributive version control has been increasingly used in fields such as software development, engineering and genetics but to date has not been applied to the reporting of clinical studies.

Methods

In this proof-of-concept study we used publically available documentation from a recently reported randomized control trial^6,7. A copy of the clinicaltrials.gov study protocol was prepared based on it’s pre-specified endpoints and planned analyses which was saved as an unformatted text file⁶ (Dataset 1). The document’s SHA256 digest for the text was then calculated by entering text from the trial protocol into an SHA256 calculator (Xorbin©). This was then converted into a bitcoin private key and corresponding public key using a bitcoin wallet. To do this a new account was created in Strongcoin©⁸ and the SHA256 digest used as the account password (private key). From this Strongcoin© automatically generated a corresponding Advanced Encryption Standard 256 bit public key. An arbitrary amount of bitcoin was then sent to a corresponding bitcoin address. To verify the existence of the document a second researcher was sent the originally prepared unformatted document. An SHA256 digest was created as previously described and a corresponding private key and public key generated. The exact replication of the public key (1AHjCz2oEUTH8js4S8vViC8NKph4zCACXH) was then used to prove the documents existence in the blockchain using blockchain.info©⁹. The protocol document was then edited to reflect any changes to pre-specified outcomes as reported by the COMPare group³. This was used to create a further SHA256 and corresponding public and private keys³.

Results

Incorporating a transaction into the blockchain using a public and private key generated from the SHA256 digest of the trial protocol provided a timestamped record that the protocol was at least as old as the transaction generated. The transaction took under five minutes to complete. The process cost was free as the nominal bitcoin transaction could be retrieved. Researchers were able to search for the transaction on the blockchain, confirm the date when the transaction occurred and verify the authenticity of the original protocol by generating identical public and private keys. Any changes made to the original document generated different public and private keys indicating that protocol had been altered. This included assessment of the edited protocol reflecting pre-specified outcomes not reported or non-pre-specified outcomes now reported in the final paper.

Discussion

Fraud or carelessness in scientific methods erodes the confidence in medicine as a whole which is essential to the performance of its function¹. The method described here provides an immutable record of the existence, integrity and ownership of a specific trial protocol. It is a simple and cheap way of allowing a third party to audit and externally validate outcomes and analyses specified a-priori with the findings reported a-posteriori. The method prevents researchers from changing endpoints or analyses after seeing their study results without reporting such changes. Transaction codes could be recorded in scientific papers, reference databases or trial registries to facilitate external verification. Making changes to pre-specified text in a document or trying to bury a protocol in a trial registry would simply not be possible. Attempts to fraudulently prepare multiple protocols in advance would be technically possible but would require a considerable amount of advanced planning and would leave behind a publically available trail of evidence that could not be destroyed.

The blockchain offers a number of advantages over trial registries or publishing protocols. Firstly, the blockchain would not be confined to the validation of clinical trials. The approach could be used for a whole range of observational and experimental studies where registries do not currently exist. Secondly, the blockchain provides a real-time timestamped record of a protocol. Such precision is important given persistent problems with protocol registration after trial initiation¹⁰. Thirdly, with over 30,000 trials currently published annually and rising, manual outcome verification is simply not possible¹¹.

Conclusion

The method we have described allows anyone to verify the exact wording and existence of a protocol at a given point in time. It has the potential to support automated, extremely robust verification of pre-specified and reported outcomes. This evidence should increase trust and diminish suspicion in reported data and the conclusions that are drawn.

Data availability

F1000Research: Dataset 1. Unformatted text file, 10.5256/f1000research.8114.d114596¹²